Sun, Jian; Xu, Yongchang; Gao, Rongsui; Lin, Jingxia; Wei, Wenhui; Srinivas, Swaminath; Li, Defeng; Yang, Run-Shi; Li, Xing-Ping; Liao, Xiao-Ping; Liu, Ya-Hong; Feng, Youjun
Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene, mcr-2 , was revealed soon after the discovery of the paradigm gene mcr-1 , which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood. Here we show a unique transposon unit that facilitates the acquisition and transfer of mcr-2 Evolutionary analyses suggested that both MCR-2 and MCR-1 might be traced to their cousin phosphoethanolamine (PEA) lipid A transferase from a known polymyxin producer, Paenibacillus Transcriptional analyses showed that the level of mcr-2 transcripts is relatively higher than that of mcr-1 Genetic deletions revealed that the transmembrane regions (TM1 and TM2) of both MCR-1 and MCR-2 are critical for their location and function in bacterial periplasm, and domain swapping indicated that the TM2 is more efficient than TM1. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) confirmed that all four MCR proteins (MCR-1, MCR-2, and two chimeric versions [TM1-MCR-2 and TM2-MCR-1]) can catalyze chemical modification of lipid A moiety anchored on lipopolysaccharide (LPS) with the addition of phosphoethanolamine to the phosphate group at the 4' position of the sugar. Structure-guided site-directed mutagenesis defined an essential 6-residue-requiring zinc-binding/catalytic motif for MCR-2 colistin resistance. The results further our mechanistic understanding of transferable colistin resistance, providing clues to improve clinical therapeutics targeting severe infections by MCR-2-containing pathogens. IMPORTANCE Carbapenem and colistin are the last line of
Full Text Available Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene, mcr-2, was revealed soon after the discovery of the paradigm gene mcr-1, which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood. Here we show a unique transposon unit that facilitates the acquisition and transfer of mcr-2. Evolutionary analyses suggested that both MCR-2 and MCR-1 might be traced to their cousin phosphoethanolamine (PEA lipid A transferase from a known polymyxin producer, Paenibacillus. Transcriptional analyses showed that the level of mcr-2 transcripts is relatively higher than that of mcr-1. Genetic deletions revealed that the transmembrane regions (TM1 and TM2 of both MCR-1 and MCR-2 are critical for their location and function in bacterial periplasm, and domain swapping indicated that the TM2 is more efficient than TM1. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS confirmed that all four MCR proteins (MCR-1, MCR-2, and two chimeric versions [TM1-MCR-2 and TM2-MCR-1] can catalyze chemical modification of lipid A moiety anchored on lipopolysaccharide (LPS with the addition of phosphoethanolamine to the phosphate group at the 4′ position of the sugar. Structure-guided site-directed mutagenesis defined an essential 6-residue-requiring zinc-binding/catalytic motif for MCR-2 colistin resistance. The results further our mechanistic understanding of transferable colistin resistance, providing clues to improve clinical therapeutics targeting severe infections by MCR-2-containing pathogens.
Rakesh Kumar; Baljit Jassal; Bhupinder Kumar
Emergence of resistant strain to antimicrobials is a growing problem worldwide. Here, we report a case of multidrug-resistant Klebsiella pneumoniae and Acinectobacter baumannii, Gram-negative bacilli, which was only intermediate sensitive to colistin; a polymyxin E. Colistin has attracted more interest recently because of its significant activity against multi-resistant Pseudomonas aeruginosa, A. baumannii and K. pneumoniae, and the low resistance rates to it. The decrease in sensitivity of c...
Oostdijk, Evelien A. N.; Smits, Loek; de Smet, Anne Marie G. A.; Leverstein-van Hall, Maurine A.; Kesecioglu, Jozef; Bonten, Marc J. M.
Topical use of colistin as part of selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) has been associated with improved patient outcome in intensive care units (ICU), yet little is known about the risks of colistin resistance. We quantified effects of
Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William
The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.
Bouchene, Salim; Marchand, Sandrine; Couet, William; Friberg, Lena E; Gobin, Patrice; Lamarche, Isabelle; Grégoire, Nicolas; Björkman, Sven; Karlsson, Mats O
Colistin is a polymyxin antibiotic used to treat patients infected with multidrug-resistant Gram negative bacteria (MDR-GNB). The objective of this work was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model to predict tissue distribution of colistin in rat. The distribution of a drug in a tissue is commonly characterized by its tissue-to-plasma partition coefficient, K p . Colistin and its prodrug, colistin methanesulfonate (CMS) K p priors were measured experimentally from rat tissue homogenates or predicted in silico. The PK parameters of both compounds were estimated fitting in vivo their plasma concentration-time profiles from six rats receiving an i.v. bolus of CMS. The variability in the data was quantified by applying a non-linear mixed effect (NLME) modelling approach. A WB-PBPK model was developed assuming a well-stirred and perfusion-limited distribution in tissue compartments. Prior information on tissue distribution of colistin and CMS was investigated following three scenarios: K p were estimated using in silico K p priors (I) or K p were estimated using experimental K p priors (II) or K p were fixed to the experimental values (III). The WB-PBPK model best described colistun and CMS plasma concentration-time profiles in scenario II. Colistin predicted concentrations in kidneys in scenario II were higher than in other tissues, which was consistent with its large experimental K p prior. This might be explained by a high affinity of colistin for renal parenchyma and active reabsorption into the proximal tubular cells. In contrast, renal accumulation of colistin was not predicted in scenario I. Colistin and CMS clearance estimates were in agreement with published values. The developed model suggests using experimental priors over in silico K p priors for kidneys to provide a better prediction of colistin renal distribution. Such models might serve in drug development for interspecies scaling and investigating the impact of
Marchand, Sandrine; Bouchene, Salim; de Monte, Michèle; Guilleminault, Laurent; Montharu, Jérôme; Cabrera, Maria; Grégoire, Nicolas; Gobin, Patrice; Diot, Patrice; Couet, William; Vecellio, Laurent
The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.
Full Text Available Abstract Background Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli strains, and to evaluate potential interaction. Methods Antimicrobial susceptibility, minimum inhibitory concentration (MIC and fractional inhibitory concentration index (FICI of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625. Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains. Graphical abstract Synergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.
Agersø, Yvonne; Torpdahl, Mia; Zachariasen, Camilla
. Interestingly, Salmonella Dublin and Salmonella Enteritidis belong to the same O-group (O:1, 9,12), suggesting that surface lipopolysaccharides (LPS) of the cell (O-antigen) play a role in colistin susceptibility. The epidemiological cut-off value of >2 mg/L for colistin suggested by European Committee...... on Antimicrobial Susceptibility Testing (EUCAST) is placed inside the distribution for both Salmonella Dublin and Salmonella Enteritidis. All tested Salmonella Dublin isolates, regardless of MIC colistin value, had identical pmrA and pmrB sequences. Missense mutations were found only in pmrA in one Salmonella...
Pogue, Jason M; Kaye, Keith S
Despite many theoretical and in vitro advantages, clinical data comparing combination therapy with colistin + rifampicin to colistin alone for infection due to extremely-drug resistant (XDR) Acinetobacter baumanni are scarce and limited by small numbers and/or low quality evidence. This article represents the first large, randomized, controlled, prospective study comparing colistin monotherapy and combination therapy. The reviewed article found no difference in all cause or infection related mortality, though there was an improved rate of microbiological clearance in the combination therapy arm. This study adds important new data to the literature and sets the stage for future studies that can be designed to overcome the limitations of this study, which are discussed in detail below. Based on this study, we cannot say definitively that combination therapy is not warranted for treatment of invasive infection due to A. baumannii, but the results do suggest that rifampicin is not an ideal agent to be combined with colistin.
Karaiskos, Ilias; Friberg, Lena E.; Pontikis, Konstantinos; Ioannidis, Konstantinos; Tsagkari, Vasiliki; Galani, Lamprini; Kostakou, Eirini; Baziaka, Fotini; Paskalis, Charalambos; Koutsoukou, Antonia; Giamarellou, Helen
Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents ...
Full Text Available Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1. However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.
Kolpen, Mette; Appeldorff, Cecilie F.; Brandt, Sarah
that production of OH˙may not contribute significantly to the bactericidal activity of colistin on P. aeruginosa biofilm. Thus, we investigated the effect of colistin treatment on biofilm of wild-type PAO1, a catalase-deficient mutant (katA) and a colistin-resistant CF isolate cultured in microtiter plates...
Karaiskos, Ilias; Friberg, Lena E; Pontikis, Konstantinos; Ioannidis, Konstantinos; Tsagkari, Vasiliki; Galani, Lamprini; Kostakou, Eirini; Baziaka, Fotini; Paskalis, Charalambos; Koutsoukou, Antonia; Giamarellou, Helen
Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430-3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241- 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284-3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼ 270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while
Excess Mortality Associated With Colistin-Tigecycline Compared With Colistin-Carbapenem Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia: A Multicenter Prospective Observational Study.
Cheng, Aristine; Chuang, Yu-Chung; Sun, Hsin-Yun; Sheng, Wang-Huei; Yang, Chia-Jui; Liao, Chun-Hsing; Hsueh, Po-Ren; Yang, Jia-Ling; Shen, Ni-Jiin; Wang, Jann-Tay; Hung, Chien-Ching; Chen, Yee-Chun; Chang, Shan-Chwen
Since few therapeutic options exist for extensively drug resistant Acinetobacter baumannii, an emerging threat in ICUs worldwide, and comparative prospective studies of colistin-based combination therapies are lacking, our objective was to compare the outcomes of patients with extensively drug-resistant A. baumannii bacteremia, treated with colistin-carbapenem and colistin-tigecycline combinations. Prospective, observational, multicenter study. Adults with extensively drug-resistant A. baumannii bacteremia were prospectively followed from 2010 to 2013 at three hospitals in Taiwan. Extensively drug-resistant A. baumannii was defined as A. baumannii (genospecies 2) nonsusceptible to all drug classes except for colistin and tigecycline, and standard combination therapy as use of parenteral colistin-carbapenem or colistin-tigecycline for at least 48 hours after onset of bacteremia. Primary outcome measure was 14-day mortality. Of the 176 episodes of extensively drug-resistant A. baumannii bacteremia evaluated, 55 patients with a median (interquartile range) age of 62 years (44-79 yr) and Sequential Organ Failure Assessment score of 9 (5-13) points received standard combination therapy: colistin-tigecycline in 29 patients and colistin-carbapenem in 26. Crude 14-day and in-hospital mortality rates for patients receiving colistin-tigecycline versus patients receiving colistin-carbapenem were 35% versus 15% (p=0.105) and 69% versus 50% (p=0.152), respectively. Breakthrough extensively drug-resistant A. baumannii bacteremia under steady state concentrations of combination therapy for colistin-tigecycline group was 18% and for colistin-carbapenem group was 0% (p=0.059). Eleven patients (20.0%) developed nephrotoxicity. After adjusting for age, sex, comorbidity, initial disease severity, loading colistin dose, polymicrobial infection, and primary infection site, excess 14-day mortality was associated with the use of colistin-tigecycline in the subgroup with tigecycline
Kádár, Béla; Kocsis, Béla; Tóth, Ákos; Kristóf, Katalin; Felső, Péter; Kocsis, Béla; Böddi, Katalin; Szabó, Dóra
In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.
Choi, Ik Sung; Lee, Yu Ji; Wi, Yu Mi; Kwan, Byung Soo; Jung, Kae Hwa; Hong, Woong Pyo; Kim, June Myong
The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Coppi, M; Cannatelli, A; Antonelli, A; Baccani, I; Di Pilato, V; Sennati, S; Giani, T; Rossolini, G M
To evaluate a novel method, the colistin-MAC test, for phenotypic screening of acquired colistin resistance mediated by transferable mcr-1 resistance determinants, based on colistin MIC reduction in the presence of dipicolinic acid (DPA). The colistin-MAC test consists in a broth microdilution method, in which colistin MIC is tested in the absence or presence of DPA (900 μg/mL). Overall, 74 colistin-resistant strains of Enterobacteriaceae (65 Escherichia coli and nine other species), including 61 strains carrying mcr-1-like genes and 13 strains negative for mcr genes, were evaluated with the colistin-MAC test. The presence of mcr-1-like and mcr-2-like genes was assessed by real-time PCR and end-point PCR. For 20 strains, whole-genome sequencing data were also available. A ≥8-fold reduction of colistin MIC in the presence of DPA was observed with 59 mcr-1-positive strains, including 53 E. coli of clinical origin, three E. coli transconjugants carrying MCR-1-encoding plasmids, one Enterobacter cloacae complex and two Citrobacter spp. Colistin MICs were unchanged, increased or at most reduced by twofold with the 13 mcr-negative colistin-resistant strains (nine E. coli and four Klebsiella pneumoniae), but also with two mcr-1-like-positive K. pneumoniae strains. The colistin-MAC test could be a simple phenotypic test for presumptive identification of mcr-1-positive strains among isolates of colistin-resistant E. coli, based on a ≥8-fold reduction of colistin MIC in the presence of DPA. Evaluation of the test with a larger number of strains, species and mcr-type resistance determinants would be of interest. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Snesrud, Erik; Maybank, Rosslyn; Kwak, Yoon I; Jones, Anthony R; Hinkle, Mary K; Mc Gann, Patrick
Whole genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn 3 -like transposon in P. aeruginosa MRSN 12280. The isolate was non-susceptible to colistin by broth microdilution and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge, this is the first report of mcr in colistin non-susceptible P. aeruginosa .
Suh, Ji-Yoeun; Son, Jun Seong; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Song, Jae-Hoon
In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading. PMID:19752282
Trung, N.V.; Matamoros, S.; Carrique-Mas, J.J.; Nghia, N.H.; Nhung, N.T.; Chieu, T.T.B.; Mai, H.H.; Van Rooijen, W.; Campbell, J.; Wagenaar, J.A.; Hardon, A.; Mai, N.T.N.; Hieu, T.Q.; Thwaites, G.; de Jong, M.D.; Schultsz, C.; Hoa, N.T.
We investigated the consequences of colistin use in backyard chicken farms in Vietnam by examining the prevalence of mcr-1 in fecal samples from chickens and humans. Detection of mcr-1–carrying bacteria in chicken samples was associated with colistin use and detection in human samples with exposure
Trung, Nguyen Vinh; Matamoros, Sébastien; Carrique-Mas, Juan J.; Nghia, Nguyen Huu; Nhung, Nguyen Thi; Chieu, Tran Thi Bich; Mai, Ho Huynh; van Rooijen, Willemien; Campbell, James; Wagenaar, Jaap A.; Hardon, Anita; Mai, Nguyen Thi Nhu; Hieu, Thai Quoc; Thwaites, Guy; de Jong, Menno D.; Schultsz, Constance; Hoa, Ngo Thi
We investigated the consequences of colistin use in backyard chicken farms in Vietnam by examining the prevalence of mcr-1 in fecal samples from chickens and humans. Detection of mcr-1-carrying bacteria in chicken samples was associated with colistin use and detection in human samples with exposure
Dafopoulou, Konstantina; Xavier, Basil Britto; Hotterbeekx, An; Janssens, Lore; Lammens, Christine; Dé, Emmanuelle; Goossens, Herman; Tsakris, Athanasios; Malhotra-Kumar, Surbhi
In two pairs of clinical colistin-susceptible/colistin-resistant (Csts/Cstr) Acinetobacter baumannii strains, the Cstr strains showed significantly decreased biofilm formation in static and dynamic assays (P Cstr strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other. PMID:26666921
Colistin (polymyxin E) is a cationic polypeptide antibiotic that has broad-spectrum activity against Gram-negative bacteria. It is classified as critically important in human medicine for treating hard-to-treat multi-drug resistant infections. Recently a plasmid-mediated colistin resistance gene (mc...
M. Tsala (Marilena); S. Vourli (Sophia); Georgiou, P.-C. (Panagiota-Christina); S. Pournaras (Spyros); A. Tsakris (Athanassios); G.L. Daikos (George); J.W. Mouton (Johan); J. Meletiadis (Joseph)
textabstractObjectives: Because the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of colistin against Enterobacteriaceae are not well explored, we studied the activity of colistin against K. pneumoniae in an in vitro PK/PD model simulating different dosing regimens. Methods: Three clinical
Hengzhuang, Wang; Wu, Hong; Ciofu, Oana
The time course activity of Colistin and Imipenem on mucoid and non-mucoid biofilm-growing P. aeruginosa showed that compared with planktonic bacteria, the kinetics of Colistin and Imipenem retained the concentration- and time-dependent killings, respectively but higher doses of antibiotics and f...
Nguyen Gia Binh
Conclusion: A personalized dosing protocol of colistin was effective, with low nephrotoxicity, among critically ill Vietnamese patients with low body weight. Further studies are warranted for assessing the efficacy and toxicity in a larger cohort.
Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing
The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Full Text Available Colistin (Polymyxin E is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant (MDR Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum- β-lactamase (ESBL genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close
Rhouma, Mohamed; Beaudry, Francis; Thériault, William; Letellier, Ann
Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa , and Klebsiella pneumoniae . Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum-β-Lactamase genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close cooperation between physicians
Karbuz, Adem; Özdemir, Halil; Yaman, Ayhan; Kocabaş, Bilge Aldemir; Odek, Çağlar; Güriz, Haluk; Aysev, Ahmet Derya; Çiftçi, Ergin; Kendirli, Tanil; Ateş, Can; İnce, Erdal
Colistin is active against most multidrug-resistant, aerobic Gram-negative bacteria. Because of the reported nephrotoxicity during the first years of use of colistin, there were concerns of its use in pediatrics where there was limited experience The aim of this study is to document the clinical characteristics and outcomes of use of colistin in pediatric patients at a pediatric intensive care unit in Turkey. We reviewed the medical and laboratory records of 29 critically ill children who were treated with colistin for 38 courses between January 2011 and December 2011 at the Department of Pediatric Intensive Care Unit in Ankara University Medical School, Turkey. The median age was 17 months (range 3-217 months). Male-to-female ratio was 1:1.37. Ventilator-associated pneumonia (21 courses) was the leading diagnosis followed by catheter-related blood stream infection (6 courses), bacteremia (4 courses), ventriculoperitoneal shunt infection, peritonitis and pneumonia (1 course). The most commonly isolated microorganisms were Acinetobacter baumanni, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, and Enterobacter cloacae. Two colistin formulations were used. Colimycin (Kocak Farma) was used in 21 colistin treatment episodes. The median dosage of colistin in this group was 5.0 mg/kg/d (2.3-5.6 mg/kg/d). Colomycin (Forest Laboratories) was used in 17 colistin treatment episodes. The median dosage of colistin in the second group was 75,000 International Unit/kg/d (50,000-80,000 International Unit/kg/d). Thirty colistin treatment episodes (79%) had a good or partial clinical response and 8 (21%) had a poor clinical response. Of the 8 colistin treatment episodes with poor clinical response, 3 were in the Colimycin group and 5 were in the Colomycin group. Ten patients died. There was no evidence of neurotoxicity in this study. Nephrotoxicity was observed in 1 patient but was not attributed to colistin because the patient
Rhouma, Mohamed; Beaudry, Francis; Thériault, William; Letellier, Ann
Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum-β-Lactamase genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close cooperation between physicians
Domínguez-Ortega, J; Manteiga, E; Abad-Schilling, C; Juretzcke, M A; Sánchez-Rubio, J; Kindelan, C
Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm. We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.
Gundogdu, Aycan; Ulu-Kilic, Aysegul; Kilic, Huseyin; Ozhan, Esra; Altun, Dilek; Cakir, Ozlem; Alp, Emine
The antibiotic colistin, which had been previously abandoned, is being brought back as a last line of defense against bacterial infection. However, colistin resistance was reported shortly after its reintroduction. This study evaluated the risk factors for colonization/infections due to colistin-resistant Acinetobacter baumannii (ColR-Ab) and Klebsiella pneumoniae (ColR-Kp) strains and characterized the molecular epidemiology of these two strains. Age, previous hospitalization duration, and previous use of carbapenem and colistin were risk factors for ColR-Kp, whereas previous use of carbapenem and colistin was a risk factor for ColR-Ab. According to pulsed-field gel electrophoresis analysis, most ColR-Kp strains could be grouped into two major pulsotypes. This appears to be an indicator of cross contamination of ColR-Kp strain, since different isolates appeared to be belonging to the same clones. The existence of colistin-susceptible (ColS) and colistin-resistant (ColR) strains in the same pulsotypes might also be an indicator of the recent emergence of resistance mechanisms. The results highlight the emergence of ColR pathogens in Turkey, which is considered to be developing country, and that carbapenem use coupled with insufficient infection control measures might increase the risk of ColR outbreaks.
Zhao, Miao; Bulman, Zackery P; Lenhard, Justin R; Satlin, Michael J; Kreiswirth, Barry N; Walsh, Thomas J; Marrocco, Amanda; Bergen, Phillip J; Nation, Roger L; Li, Jian; Zhang, Jing; Tsuji, Brian T
KPC-producing Klebsiella pneumoniae are an emerging public health problem around the globe. We defined the combinatorial pharmacodynamics and ability to suppress resistance of two 'old' antibiotics, fosfomycin and colistin, in time-kill experiments and hollow-fibre infection models (HFIM). Two KPC-2-producing K. pneumoniae isolates were used: one susceptible to both colistin and fosfomycin (KPC 9A: MIC colistin 0.25 mg/L and MIC fosfomycin ≤8 mg/L) and the other resistant to colistin and susceptible to fosfomycin (KPC 5A: MIC colistin 64 mg/L and MIC fosfomycin 32 mg/L). Time-kill experiments assessed an array of colistin and fosfomycin concentrations against both isolates. Colistin and fosfomycin pharmacokinetics from critically ill patients were simulated in the HFIM to define the pharmacodynamic activity of humanized regimens over 5 days against KPC 9A. In time-kill experiments, synergy was demonstrated for all colistin/fosfomycin combinations containing >8 mg/L fosfomycin against the double-susceptible KPC strain, 9A. Synergy versus KPC strain 5A was only achieved at the highest concentrations of colistin (4 mg/L) and fosfomycin (512 mg/L) at 48 h. In the HFIM, colistin or fosfomycin monotherapies resulted in rapid proliferation of resistant subpopulations; KPC 9A regrew by 24 h. In contrast to the monotherapies, the colistin/fosfomycin combination resulted in a rapid 6.15 log 10 cfu/mL reduction of KPC 9A by 6 h and complete suppression of resistant subpopulations until 120 h. Colistin and fosfomycin may represent an important treatment option for KPC-producing K. pneumoniae otherwise resistant to traditional antibiotics. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: email@example.com.
Ajiboye, Taofeek O; Skiebe, Evelyn; Wilharm, Gottfried
Phenolic acids with catechol groups are good prooxidants because of their low redox potential. In this study, we provided data showing that phenolic acids, caffeic acid, gallic acid and protocatechuic acid, enhanced colistin-mediated bacterial death by inducing redox imbalance. The minimum inhibitory concentrations of these phenolic acids against Acinetobacter baumannii AB5075 were considerably lowered for ΔsodB and ΔkatG mutants. Checkerboard assay shows synergistic interactions between colistin and phenolic acids. The phenolic acids exacerbated colistin-induced oxidative stress in A. baumannii AB5075 through increased superoxide anion generation, NAD + /NADH and ADP/ATP ratio. In parallel, the level of reduced glutathione was significantly lowered. We conclude that phenolic acids potentiate colistin-induced oxidative stress in A. baumannii AB5075 by increasing ROS generation, energy metabolism and electron transport chain activity with a concomitant decrease in glutathione. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Tada, Tatsuya; Nhung, Pham Hong; Shimada, Kayo; Tsuchiya, Mitsuhiro; Phuong, Doan Mai; Anh, Nguyen Quoc; Ohmagari, Norio; Kirikae, Teruo
The mcr-1 was first detected on a plasmid in colistin-resistant Escherichia coli from livestock and patients in China. We described here the emergence of colistin-resistant E. coli clinical isolates harboring mcr-1 on the chromosomes in Vietnam. To our knowledge, this is the first report of hospital-acquired E. coli isolates harboring mcr-1 in a medical setting in Vietnam. Copyright © 2017. Published by Elsevier Ltd.
Dai, Chongshan; Ciccotosto, Giuseppe D; Cappai, Roberto; Wang, Yang; Tang, Shusheng; Xiao, Xilong; Velkov, Tony
Neurotoxicity is an adverse effect patients experience during colistin therapy. The development of effective neuroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. The present study investigates the neuroprotective effect of the synergistic tetracycline antibiotic minocycline against colistin-induced neurotoxicity. The impact of minocycline pretreatment on colistin-induced apoptosis, caspase activation, oxidative stress and mitochondrial dysfunction were investigated using cultured mouse neuroblastoma-2a (N2a) and primary cortical neuronal cells. Colistin-induced neurotoxicity in mouse N2a and primary cortical cells gives rise to the generation of reactive oxygen species (ROS) and subsequent cell death via apoptosis. Pretreatment of the neuronal cells with minocycline at 5, 10 and 20 μM for 2 h prior to colistin (200 μM) exposure (24 h), had an neuroprotective effect by significantly decreasing intracellular ROS production and by upregulating the activities of the anti-ROS enzymes superoxide dismutase and catalase. Minocycline pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation and subsequent apoptosis. Immunohistochemical imaging studies revealed colistin accumulates within the dendrite projections and cell body of primary cortical neuronal cells. To our knowledge, this is first study demonstrating the protective effect of minocycline on colistin-induced neurotoxicity by scavenging of ROS and suppression of apoptosis. Our study highlights that co-administration of minocycline kills two birds with one stone: in addition to its synergistic antimicrobial activity, minocycline could potentially ameliorate unwanted neurotoxicity in patients undergoing polymyxin therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions
Full Text Available Eulalia Sans-Serramitjana,1 Marta Jorba,1 José Luis Pedraz,2 Teresa Vinuesa,1 Miguel Viñas1 1Laboratory of Molecular Microbiology and Antimicrobials, Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, 2Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU, Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Vitoria, Spain Abstract: The emergence of colistin-resistant Pseudomonas aeruginosa in cystic fibrosis (CF patients, particularly after long-term inhalation treatments, has been recently reported. Nanoencapsulation may enable preparations to overcome the limitations of conventional pharmaceutical forms. We have determined the time-dependent viability of P. aeruginosa biofilms treated with both free and nanoencapsulated colistin. We also examined the relationship between the optimal anti-biofilm activity of nanostructured lipid carrier (NLC-colistin and the structural organization of the biofilm itself. The results showed the more rapid killing of P. aeruginosa bacterial biofilms by NLC-colistin than by free colistin. However, the two formulations did not differ in terms of the final percentages of living and dead cells, which were higher in the inner than in the outer layers of the treated biofilms. The effective anti-biofilm activity of NLC-colistin and its faster killing effect recommend further studies of its use over free colistin in the treatment of P. aeruginosa infections in CF patients. Keywords: cystic fibrosis, colistin sulfate, lipid nanoparticles, P. aeruginosa, confocal laser scanning microscopy, anti-biofilm activity
Morales, Adriano Savoia; Fragoso de Araújo, Juliana; de Moura Gomes, Vasco Túlio; Reis Costa, Adrienny Trindade; dos Prazeres Rodrigues, Dália; Porfida Ferreira, Thais Sebastiana; de Lima Filsner, Pedro Henrique Nogueira; Felizardo, Maria Roberta; Micke Moreno, Andrea
Reports about acquired resistance to colistin in different bacteria species are increasing, including E. coli of animal origin, but reports of resistance in wild S. enterica of different serotypes from swine are not found in the literature. Results obtained with one hundred and twenty-six E. coli strains from diseased swine and one hundred and twenty-four S. enterica strains from diseased and carrier swine showed a frequency of 6.3% and 21% of colistin-resistant strains, respectively. When comparing the disk diffusion test with the agar dilution test to evaluate the strains, it was confirmed that the disk diffusion test is not recommended to evaluate colistin resistance as described previously. The colistin MIC 90 and MIC 50 values obtained to E. coli were 0.25 μg/mL and 0.5 μg/mL, the MIC 90 and MIC 50 to S. enterica were 1 μg/mL and 8 μg/mL. Considering the importance of colistin in control of nosocomial human infections with Gram-negative multiresistant bacteria, and the large use of this drug in animal production, the colistin resistance prevalence in enterobacteriaceae of animal origin must be monitored more closely.
Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier
Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
In vitro activity of colistin mono- and combination therapy against colistin-resistant Acinetobacter baumannii, mechanism of resistance, and clinical outcomes of patients infected with colistin-resistant A. baumannii at a Thai university hospital
Full Text Available Yongyut Lertsrisatit,1 Wichai Santimaleeworagun,2,3 Sudaluck Thunyaharn,4 Jantima Traipattanakul5 1College of Pharmacotherapy Thailand, Nonthaburi, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 3Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group (PIRBIG Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, Thailand; 4Faculty of Medical Technology, Nakhonratchasima College, Nakhonratchasima, Thailand; 5Division of Infectious Disease, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand Purpose: Colistin is a drug of last resort for treating multidrug-resistant Acinetobacter baumannii infections. Unfortunately, colistin-resistant A. baumannii (CoR-AB has been reported. Here, we examined the in vitro effect of mono- and combined antimicrobials against CoR-AB strains and their resistance mechanism, and evaluated the clinical outcomes of CoR-AB-infected patients.Patients and methods: Seventeen clinical CoR-AB strains were isolated from patients at Phramongkutklao hospital, 2011–2015. The mono- and synergistic activities of colistin, tigecycline, sulbactam, imipenem, meropenem, amikacin, fosfomycin, and cotrimoxazole were examined by minimum inhibitory concentration (MIC and fractional inhibitory concentration index. Clonal relationship and resistance genes were determined by repetitive extragenic palindromic polymerase chain reaction with specific primers. The effect of carbonyl cyanide 3-chlorophenylhydrazone combined with colistin was used to test efflux pump involvement. Patient treatment outcomes were also reported.Results: The most prevalent infection in CoR-AB patients was pneumonia (35.3%, and all patients were administered colistin combined with another agent. The 30-day mortality was 70.6%, and the colistin MIC range and MIC50 was 16–512 µg/mL and 64 µg/mL, respectively. All CoR-AB strains were sensitive to tigecycline
Mehmet Sah Ä°pek
Full Text Available Background: The aim of this study was to assess the safety and efficacy of colistin use in critically ill neonates. Methods: This was a caseâcontrol study that included newborn infants with proven or suspected nosocomial infections between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The clinical and laboratory characteristics and outcomes of patients who received colistin therapy were reviewed and compared to patients who were treated with antimicrobial agents other than colistin during the same period. Results: Forty-seven cases who received intravenous colistin (colistin group and 59 control patients (control group were included. There were no significant differences between the groups regarding outcomes and nephrotoxicity, including acute renal failure. Colistin therapy was associated with significantly reduced serum magnesium (1.38Â Â±Â 0.39Â mg/dL vs. 1.96Â Â±Â 0.39Â mg/dL, pÂ <Â 0.001 and hypokalemia (46.8% vs. 25.4%, pÂ =Â 0.026. The patients who received colistin also had longer hospital stays (43 (32â70 days vs. 39 (28â55 days, pÂ =Â 0.047, a higher rate of previous carbapenem exposure (40.4% vs. 11.9%, pÂ =Â 0.001, and a higher age at the onset of infection (13 (10â21 days vs. 11 (9â15 days, pÂ =Â 0.03. Conclusion: This study showed that colistin was both effective and safe for treating neonatal infections caused by multidrug-resistant gram-negative bacteria. However, intravenous colistin use was significantly associated with hypomagnesemia and hypokalemia. Key Words: colistin, neonate, nosocomial infection, multi-drug resistant, gram-negative bacteria
Dahdouh, Elias; Gómez-Gil, Rosa; Sanz, Sonia; González-Zorn, Bruno; Daoud, Ziad; Mingorance, Jesús; Suárez, Monica
Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug resistance among A. baumannii isolates led to the use of colistin, subsequently giving rise to colistin-resistant strains. In this study, the genetic and phenotypic profiles of two colistin-resistant A. baumannii isolates were investigated. Two A. baumannii isolates were obtained from Patient 1 (C071 and C440) and three isolates were obtained from Patient 2 (C080, C314 and C428). Susceptibility profiles were determined by VITEK ® 2 and Etest. Clonality was determined by RAPD analysis and trilocus multiplex PCR. The pmrCAB operon was sequenced and common carbapenemase genes were screened for by PCR. Doubling times, haemolysis, surface motility, biofilm formation, siderophore production and proteolytic activity were phenotypically determined. Finally, whole-genome sequencing was performed for all five isolates. Isolates C440 and C428 were resistant to colistin and were clonally identical to their sensitive counterparts. The cause of colistin resistance was traced to the previously described P233S mutation in pmrB of C440 and to a novel ΔI19 mutation in pmrB of C428. bla OXA-58-like and bla GES-5 from the strains of Patients 1 and 2, respectively, were also detected. C440 had attenuated proteolytic activity and was positive for siderophore production compared with C071. No difference in in vitro virulence was detected between isolates C080, C314 and C428. In conclusion, one common and one novel mutation were encountered in pmrB from two distinct colistin-resistant A. baumannii isolates. These mutations caused colistin resistance during therapy in two distinct clones, and only one of them had altered in vitro virulence. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Mohanty, Srujana; Maurya, Vijeta; Gaind, Rajni; Deb, Monorama
Pseudomonas aeruginosa and Acinetobcter spp. are important nosocomial pathogens and carbapenem resistance is an emerging threat. Therapeutic options for infections with these isolates include colistin. This study was conducted to determine the prevalence of carbapenem resistance in P. aeruginosa and Acinetobacter spp. bloodstream isolates, phenotypically characterize the resistance mechanisms and evaluate the in vitro activity of colistin. Consecutive 145 (95 P.aeruginosa and 50 Acinetobacter spp.) non-repeat isolates were included. Antibiotic susceptibility testing was performed per CLSI guidelines. MIC for carbapenems and colistin was performed using Etest. Isolates showing reduced susceptibility or resistance to the carbapenems were tested for metallo-β-lactamase (MBL) production using imipenem-EDTA combined disk and MBL Etest. Carbapenem resistance was observed in 40% P. aeruginosa and 66.0% Acinetobacter spp. Carbapenem-resistant (CA-R) isolates were significantly (p carbapenem-susceptible isolates. Approximately half of the CA-R strains were multidrug-resistant, and 3.1-5.5% were resistant to all antibiotics tested. MBL was found in 76.3% and 69.7% of the P. aeruginosa and Acinetobacter spp., respectively. Colistin resistance was observed in three (6.0%) Acinetobacter isolates and eight (8.4%) P. aeruginosa. MIC50 for carbapenems were two to four times higher for MBL-positive compared to MBL-negative isolates, but no difference was seen in MIC for colistin. Carbapenem resistance was observed to be mediated by MBL in a considerable number of isolates. Colistin is an alternative for infections caused by CA-R isolates; however, MIC testing should be performed whenever clinical use of colistin is considered.
Karaaslan, Ayşe; Çağan, Eren; Kadayifci, Eda Kepenekli; Atıcı, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; Demir, Sevliya Öcal; Soysal, Ahmet; Bakır, Mustafa
The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. This study has a retrospective study design. Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it
Full Text Available Background: The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. Aims: In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. Study Design: This study has a retrospective study design. Methods: Sixty-one critically ill children were identified through the department’s patient files archive during the period from January 2011 to November 2014. Results: Twenty-nine females and thirty-two males with a mean±standard deviation (SD age of 61±9 months (range 0-216, median 12 months received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7% was the leading diagnosis, followed by pneumonia (n=19, 31%, clinical sepsis (n=7, 11.4%, wound infection (n=6, 9.8%, urinary tract infection (n=5, 8.1% and meningitis (n=1, 1.6%. All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%, Pseudomonas aeruginosa (n=17, 27.8%, Klebsiella pneumoniae (n=6, 9.8%, K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%, K. pneumoniae and A. baumanni (n=1, 1.6%, K. oxytoca (n=1, 1.6% and Enterobacter cloacae (n=1, 1.6%. In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45. Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82, ampicillin-sulbactam (n=5, 8%, quinolones (n=5, 8%, rifampicin (n=1, 1.6%. Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin
Lin, Ming-Feng; Lin, Yun-You; Lan, Chung-Yu
Efflux pumps play an important role in antimicrobial resistance for Acinetobacter baumannii. However, the function of the Emr pump system and the relationship between Emr and drug resistance has not been characterized in A. baumannii. In this study, four possible groups of emr-like genes were found by searching a genome database. Among them, A1S_1772 (emrB) and A1S_1773 (emrA) were demonstrated to be co-transcribed as a single operon. Moreover, during osmotic stress, A1S_1772 showed the largest change in gene expression compared to the other emrB-like genes, and deletion of A1S_1772 (AB ΔemrB) significantly slowed cell growth in 20% sucrose. Using a phenotypic microarray analysis, the AB ΔemrB mutant was more susceptible to colistin and nafcillin, paromomycin, spiramycin, and D,L-serine hydroxmate than the wild type. The spot assay, time kill assay and minimal inhibition concentration determination also indicated that the wild type could tolerate colistin better than the AB ΔemrB mutant. Finally, the increased expression levels of all emrB-like genes, including A1S_0775, A1S_0909, A1S_1772, and A1S_1799, in colistin resistance-induced A. baumannii further supported the possible involvement of the emrB genes in A. baumannii colistin resistance. Together, the Emr pump systems in A. baumannii contribute to adaptation to osmotic stress and resistance to colistin.
de Maio Carrillho, Claudia M D; Gaudereto, Juliana J; Martins, Roberta Cristina Ruedas; de Castro Lima, Victor Augusto Camarinha; de Oliveira, Larissa M; Urbano, Mariana R; Perozin, Jamile S; Levin, Anna Sara; Costa, Silvia F
We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE. Copyright © 2016 Elsevier Inc. All rights reserved.
Sinirtaş, Melda; Akalin, Halis; Gedikoğlu, Suna
In recent years there has been an increase in life-threatening infections caused by Acinetobacter baumannii with multiple antibiotic resistance, which has lead to the use of polymyxins, especially colistin, being reconsidered. The aim of this study was to investigate the colistin sensitivity of A. baumannii isolates with multiple antibiotic resistance via different methods, and to evaluate the disk diffusion method for colistin against multi-resistant Acinetobacter isolates, in comparison to the E-test and Phoenix system. The study was carried out on 100 strains of A. baumannii (colonization or infection) isolated from the microbiological samples of different patients followed in the clinics and intensive care units of Uludağ University Medical School between the years 2004 and 2005. Strains were identified and characterized for their antibiotic sensitivity by Phoenix system (Becton Dickinson, Sparks, MD, USA). In all studied A. baumannii strains, susceptibility to colistin was determined to be 100% with the disk diffusion, E-test, and broth microdilution methods. Results of the E-test and broth microdilution method, which are accepted as reference methods, were found to be 100% consistent with the results of the disk diffusion tests; no very major or major error was identified upon comparison of the tests. The sensitivity and the positive predictive value of the disk diffusion method were found to be 100%. Colistin resistance in A. baumannii was not detected in our region, and disk diffusion method results are in accordance with those of E-test and broth microdilution methods.
Høi, L.; Dalsgaard, Inger; Dalsgaard, A.
An improved selective medium, cellobiose-colistin (CC) agar, gave a significantly higher (P agar, In a total of 446 alkaline peptone water preenrichments amended...... with polymyxin B, V. vulnificus was isolated from 154 preenrichments (35%) with mCPC agar and from 179 preenrichments (40%) with CC agar. CC agar gave a higher plating efficiency of V. vulnificus cells than did cellobiose-polymyxin B-colistin (CPC) agar, mCPC agar, or thiosulfate-citrate-bile salts-sucrose (TCBS......) agar; the only significant difference was observed with TCBS agar, which gave much lower plating efficiencies than the other selective media. Determination of MICs demonstrated that the concentrations of colistin and polymyxin B in CPC agar inhibit growth of a proportion of V. vulnificus strains....
Couet, W; Grégoire, N; Gobin, P; Saulnier, P J; Frasca, D; Marchand, S; Mimoz, O
Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.
Conclusions: XDR AB-VAP is endemic in our ICU without a definite factor associated with increased risk of infection. Given that almost half of the strains are also resistant to tigecycline, colistin appears to be an appropriate first-line antimicrobial drug in critically ill patients developing VAP based on invitro results.
Muhammad Kashif Saleemi
Full Text Available The current study was designed to probe pathological effects of colistin in growing broilers. One hundred twenty day-old broiler chicks were divided into six equal groups A-F. These birds were injected colistin sulphate, 0, 5, 10, 20, 40 and 80 mg/kg BW respectively through intramuscular route. The different serum-biochemical parameters including total protein, albumen, globulin, ALT, AST, LDH, GGT, creatinine and BUN were determined at day 21 and 42 of experiment. The hematological parameters including RBC, WBC, PCV and Hb were determined twice. The serum total protein values were significantly higher in group E as compared with control group. At day 42 groups, C-E had significantly lower albumen values as compared to group A. The similar pattern was observed in globulin values. The creatinine & urea was also found significantly higher in group D and E at day 21 of experiment, while at day 42 all the groups having significantly higher urea level in comparison with group A indicating nephrotoxic effect of colistin. The serum enzymes including ALT and AST were significantly higher in group D & E as compared with group A, which is an indication of liver damage. The LDH and GGT values showed significantly increasing trend in experimental groups compared with control. The erythrocytes and leucocytes count were significantly higher in control and low dose groups as compared with higher colistin dose groups. It is concluded that lavish parenteral administration of colistin resulted in increased levels of hepato-renal serum indicators and lower values of hematological parameters.
Full Text Available Salima Qamar, Najma Shaheen, Sadia Shakoor, Joveria Farooqi, Kauser Jabeen, Rumina Hasan Clinical Microbiology, Department of Pathology And Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan Introduction: Management of infections with carbapenem-resistant Enterobacteriaceae (CRE is challenging. In recent times, agents such as colistin and fosfomycin have been used in combination with other antibiotics to treat such infections. In this study, we aim to seek frequency of colistin and fosfomycin resistance in CRE from Pakistan.Methods: This study was conducted at clinical laboratories, Aga Khan University Hospital. In total, 251 CRE were included in the study. Colistin minimum inhibitory concentrations (MICs were performed using broth microdilution (BMD method and VITEK® 2 system, whereas fosfomycin susceptibility was performed using Kirby–Bauer method. MIC50 and MIC90 were calculated for colistin and agreement between VITEK and BMD was also calculated.Results: Out of 251 strains colistin MIC of ≥4 µg/mL was seen in 40 (15.9%. Of these strains 20 (50% were Klebsiella pneumoniae. Colistin MIC50 and MIC90 were found to be 0.5 and 16 µg/mL, respectively. BMD and VITEK 2 showed 100% categorical agreement. Essential agreement was 88.5% with kappa score 0.733 indicating strong agreement between VITEK and BMD. 31 out of 251 (12.3% CREs were resistant to fosfomycin.Conclusion: Study shows frequency of colistin and fosfomycin resistance to be 15.9% and 12.3%, respectively. In countries where rate of CREs is high, emerging resistance against these last resort antibiotics is alarming as it leaves clinicians with almost no options to manage such multidrug resistant and extensively drug resistant infections. Keywords: emerging drug resistance, colistin resistance, fosfomycin resistance, carbapenam resistant enterobacteriaceae, salvage antibiotics
Full Text Available The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae carbapenemase - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp genes (ompK35 and ompK36 were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.
Ben-Ami, Ronen; Lewis, Russell E.; Tarrand, Jeffrey; Leventakos, Konstantinos; Kontoyiannis, Dimitrios P.
In immunosuppressed hosts, mucormycosis is a life-threatening infection with few treatment options. We studied the activity of colistin (polymyxin E) against Mucorales species in vitro and in a murine model of pulmonary Rhizopus oryzae infection. Colistin exhibited fungicidal activity in vitro against Mucorales spores and mycelia. At the colistin MIC, initial R. oryzae hyphal damage was followed by rapid regrowth; however, regrowth was prevented by combining colistin with a subinhibitory concentration of amphotericin B. Using electron microscopy and FM4-64 staining, we demonstrated that colistin disrupts R. oryzae cytoplasmic and vacuolar membranes, resulting in the leakage of intracellular contents. The prophylactic intranasal treatment of immunosuppressed mice with colistimethate significantly reduced the mortality rate and pulmonary fungal burden resulting from inhalational challenge with R. oryzae spores, whereas intraperitoneal colistimethate treatment had no effect. We conclude that colistin has modest in vitro and in vivo fungicidal activity against Mucorales spp. Further studies are warranted to assess the use of this drug in the prevention and treatment of mucormycosis. PMID:19858263
Ben-Ami, Ronen; Lewis, Russell E; Tarrand, Jeffrey; Leventakos, Konstantinos; Kontoyiannis, Dimitrios P
In immunosuppressed hosts, mucormycosis is a life-threatening infection with few treatment options. We studied the activity of colistin (polymyxin E) against Mucorales species in vitro and in a murine model of pulmonary Rhizopus oryzae infection. Colistin exhibited fungicidal activity in vitro against Mucorales spores and mycelia. At the colistin MIC, initial R. oryzae hyphal damage was followed by rapid regrowth; however, regrowth was prevented by combining colistin with a subinhibitory concentration of amphotericin B. Using electron microscopy and FM4-64 staining, we demonstrated that colistin disrupts R. oryzae cytoplasmic and vacuolar membranes, resulting in the leakage of intracellular contents. The prophylactic intranasal treatment of immunosuppressed mice with colistimethate significantly reduced the mortality rate and pulmonary fungal burden resulting from inhalational challenge with R. oryzae spores, whereas intraperitoneal colistimethate treatment had no effect. We conclude that colistin has modest in vitro and in vivo fungicidal activity against Mucorales spp. Further studies are warranted to assess the use of this drug in the prevention and treatment of mucormycosis.
Herrmann, G.; Yang, Liang; Wu, H.
Background. Antibiotic combination therapy might be more efficient than single antibiotics to combat Pseudomonas aeruginosa biofilms in the airways of patients with cystic fibrosis. We tested the ability of colistin sulphatetobramycin combinations and single antibiotics to kill P. aeruginosa...... biofilms. Methods. P. aeruginosa biofilms were generated in vitro and in rat lungs. In a pilot study, 5 patients with cystic fibrosis inhaled colistin and then tobramycin for 4 weeks. The changes in P. aeruginosa counts and lung function were assessed before and after therapy. Results. Antibiotic...... combination therapy significantly reduced the number of P. aeruginosa cells in P. aeruginosa biofilm models in vitro. When rats were challenged with 1 x 10(7) cfu of P. aeruginosa, which was embedded in alginate beads, mortality rates, lung pathologic findings, and bacterial colony-forming unit counts were...
Brochmann, Rikke Prejh; Toft, Anders; Ciofu, Oana
The bactericidal effect of several major types of antibiotics has recently been demonstrated to be dependent on the formation of toxic amounts of hydroxyl radicals (OH·) resulting from oxidative stress in metabolically active cells. Since killing by the antimicrobial peptide colistin does...... not require bacterial metabolic activity, we tested whether the bactericidal effect of colistin depends on the formation of OH·. In Pseudomonas aeruginosa cultures, OH-mediated killing by ciprofloxacin was demonstrated by decreased bacterial survival and induction of 3'-(p-hydroxyphenyl) fluorescein (HPF......) fluorescence. OH·-mediated killing by ciprofloxacin was further confirmed by rescue of cells and reduction of HPF fluorescence due to prevention of OH· accumulation by scavenging with thiourea, by chelating with dipyridyl, by decreasing metabolism as well as by anoxic growth. In contrast, no formation of OH...
Full Text Available This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity.
Manohar, Prasanth; Shanthini, Thamaraiselvan; Ayyanar, Ramankannan; Bozdogan, Bulent; Wilson, Aruni; Tamhankar, Ashok J; Nachimuthu, Ramesh; Lopes, Bruno S
The occurrence of carbapenem- and colistin-resistance among Gram-negative bacteria is increasing worldwide. The aim of this study was to understand the distribution of carbapenem- and colistin-resistance in two areas in Tamil Nadu, India. The clinical isolates (n=89) used in this study were collected from two diagnostic centres in Tamil Nadu, India. The bacterial isolates were screened for meropenem- and colistin-resistance. Further, resistance genes blaNDM-1, blaOXA-48-like, blaIMP, blaVIM, blaKPC, mcr-1 and mcr-2 and integrons were studied. The synergistic effect of meropenem in combination with colistin was assessed. A total of 89 bacterial isolates were studied which included Escherichia coli (n=43), Klebsiella pneumoniae (n=18), Pseudomonas aeruginosa (n=10), Enterobacter cloacae (n=6), Acinetobacter baumannii (n=5), Klebsiella oxytoca (n=4), Proteus mirabilis (n=2) and Salmonella paratyphi (n=1). MIC testing showed that 58/89 (65 %) and 29/89 (32 %) isolates were resistant to meropenem and colistin, respectively, whereas 27/89 (30 %) isolates were resistant to both antibiotics. Escherichia coli, K. pneumoniae, K. oxytoca, Pseudomonas aeruginosa, and Enterobacter cloacae isolates were blaNDM-1-positive (n=20). Some strains of Escherichia coli, K. pneumoniae and K. oxytoca were blaOXA-181-positive (n=4). Class 1, 2 and 3 integrons were found in 24, 20 and 3 isolates, respectively. Nine NDM-1-positive Escherichia coli strains could transfer carbapenem resistance via plasmids to susceptible Escherichia coli AB1157. Meropenem and colistin showed synergy in 10/20 (50 %) isolates by 24 h time-kill studies. Our results highlight the distribution of carbapenem- and colistin-resistance in Gram-negative bacteria isolated from the Tamil Nadu region in South India.
Tsai, I-Lin; Kuo, Ching-Hua; Sun, Hsin-Yun; Chuang, Yu-Chung; Chepyala, Divyabharathi; Lin, Shu-Wen; Tsai, Yun-Jung
Outbreaks of multidrug-resistant Gram-negative bacterial infections have been reported worldwide. Colistin, an antibiotic with known nephrotoxicity and neurotoxicity, is now being used to treat multidrug-resistant Gram-negative strains. In this study, we applied an on-spot internal standard addition approach coupled with an ultra high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify colistin A and B from dried blood spots (DBSs). Only 15μL of whole blood was required for each sample. An internal standard with the same yield of extraction recoveries as colistin was added to the spot before sample extraction for accurate quantification. Formic acid in water (0.15%) with an equal volume of acetonitrile (50:50v/v) was used as the extraction solution. With the optimized extraction process and LC-MS/MS conditions, colistin A and B could be quantified from a DBS with respective limits of quantification of 0.13 and 0.27μgmL -1 , and the retention times were spot internal standard addition approach which benefited the precision and accuracy. Results showed that DBS sampling coupled with the sensitive LC-MS/MS method has the potential to be an alternative approach for colistin quantification, where the bias of prodrug hydrolysis in liquid samples is decreased. Copyright © 2017 Elsevier B.V. All rights reserved.
Bergen, Phillip J.; Forrest, Alan; Bulitta, Jürgen B.; Tsuji, Brian T.; Sidjabat, Hanna E.; Paterson, David L.; Li, Jian; Nation, Roger L.
The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in Pseudomonas aeruginosa. The aim of this study was to systematically investigate in vitro bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼106 and ∼108 CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 106-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 108-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 106- and 108-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations. PMID:21876058
Full Text Available Purpose: To evaluate colistin use according to global standard drug consumption in intensive care units of a referral hospital in Shiraz, Iran Methods: A prospective, interventional study was performed during an 11 month period on 100 patients admitted to ICUs of a teaching hospital being treated with colistin for at least 3 subsequent doses. Required demographic, clinical, and paraclinical data were gathered by a pharmacist. Fifteen indexes were considered to evaluate colistin use. A clinical pharmacist reviewed indication and dose of colistin at the time of prescribing this agent. Results: In our study population, pneumonia (69% was the main indication of colistin. In 87% of patients, colistin administration was based on microbiological laboratory evidence. Continuation of therapy was inappropriate in 5% of cases. By the intervention of the clinical pharmacist, colistin was discontinued in all patients in whom empirical therapy was continued incorrectly. None of the patients received loading dose of colistin. The maintenance dose, dose interval, and duration of treatment of colistin were appropriate in 76%, 71%, and 100% of patients, respectively. For none of the patients, the pharmacokinetic dosing method was used. In all patients, serum creatinine and WBC count were evaluated on daily basis. The sum indexes of colistin use were relevant to standard guidelines in 67.33% of the cases.Conclusion: The results of this study highlight the necessity of the pharmaceutical care team participation in all stages of treatment with antibiotics. After pharmacist interventions, some criteria of colistin utilization were corrected and brought closer to standard values.
Mavroidi, Angeliki; Katsiari, Maria; Likousi, Sofia; Palla, Eleftheria; Roussou, Zoi; Nikolaou, Charikleia; Maguina, Asimina; Platsouka, Evangelia D
The emergence of colistin resistance may further contribute to treatment failure of infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae. The colistin resistance rates were determined and colistin-resistant carbapenemase-producing K. pneumoniae (COL-R CP-Kp) were characterized over an 18-month period in a Greek hospital. Out of 135 carbapenemase producers, 19 isolates (14%) were categorized as resistant to colistin. Phenotypic and molecular characterization of the COL-R CP-Kp isolates revealed that all were MDR blaKPC producers and, excluding one isolate of MLST ST383, belonged to the international clonal lineage ST258. Furthermore, PCR amplification and sequencing of the mgrB locus revealed nucleotide sequences of different sizes and insertions of IS1- and IS5-like mobile elements. The majority (63%) of the COL-R blaKPC producers was recovered from patients in the intensive care unit (ICU) and clinical data indicated that all patients should have acquired these isolates in the ICU. The findings of the present study underscore a concerning evolution of colistin resistance in a setting of high K. pneumoniae carbapenemase (KPC)-Kp endemicity, such as Greece. Thus, continuous surveillance, molecular characterization, prudent use of antibiotics, and implementation of infection control measures for K. pneumoniae are urgent.
Paramythiotou, E; Karakitsos, D; Aggelopoulou, H; Sioutos, P; Samonis, G; Karabinis, A
Post-surgical meningitis and/or ventriculitis caused by Gram-negative bacteria may be difficult to treat due to the emergence of multiresistant strains. Two patients with multiresistant Acinetobacter baumannii central nervous system infection, successfully treated with either intravenous and/or intraventricular colistin are presented. Unresolved issues such as dose and duration of intraventricular colistin are discussed.
Viel, Alexis; Henri, Jérôme; Bouchène, Salim; Laroche, Julian; Rolland, Jean-Guy; Manceau, Jacqueline; Laurentie, Michel; Couet, William; Grégoire, Nicolas
The objective was the development of a whole-body physiologically-based pharmacokinetic (WB-PBPK) model for colistin, and its prodrug colistimethate sodium (CMS), in pigs to explore their tissue distribution, especially in kidneys. Plasma and tissue concentrations of CMS and colistin were measured after systemic administrations of different dosing regimens of CMS in pigs. The WB-PBPK model was developed based on these data according to a non-linear mixed effect approach and using NONMEM software. A detailed sub-model was implemented for kidneys to handle the complex disposition of CMS and colistin within this organ. The WB-PBPK model well captured the kinetic profiles of CMS and colistin in plasma. In kidneys, an accumulation and slow elimination of colistin were observed and well described by the model. Kidneys seemed to have a major role in the elimination processes, through tubular secretion of CMS and intracellular degradation of colistin. Lastly, to illustrate the usefulness of the PBPK model, an estimation of the withdrawal periods after veterinary use of CMS in pigs was made. The WB-PBPK model gives an insight into the renal distribution and elimination of CMS and colistin in pigs; it may be further developed to explore the colistin induced-nephrotoxicity in humans.
Pamp, Sünje Johanna; Gjermansen, Morten; Johansen, Helle Krogh
-mediated killing in biofilms, conventional antimicrobial compounds such as ciprofloxacin and tetracycline were found to specifically kill the subpopulation of metabolically active biofilm cells, whereas the subpopulation exhibiting low metabolic activity survived the treatment. Consequently, targeting the two...... physiologically distinct subpopulations by combined antimicrobial treatment with either ciprofloxacin and colistin or tetracycline and colistin almost completely eradicated all biofilm cells....
Rebelo, Ana Rita; Bortolaia, Valeria; Kjeldgaard, Jette S.
Background and aim: Plasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriace...
Full Text Available We report a case series of post-operative endophthalmitis due to Pseudomonas aeruginosa. A total of 8 patients operated for cataract, were referred to our facility with acute onset of decreased vision 1-2 days following surgery. All patients had clinical evidence of acute exogenous endophthalmitis with severe anterior chamber exudative reaction. Ocular samples (aqueous aspirate and vitreous tap for microbiology were taken from all eyes. Microbiology from all revealed P. aeruginosa which was resistant to all antibiotics except colistin. With prompt and accurate microbiological support it was possible to control the infection in all the eyes with the use of colistin intravitreally and intravenously which to the best of our knowledge, has been never reported. Intravitreal injection of colistin could be an option effective in the management of multi-drug-resistant endophthalmitis caused by Gram-negative bacteria.
Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.
Full Text Available Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB. Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC for meropenem (MIC ≤ 32 mg/L, combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.
Wu, Hong; Ciofu, Oana; Song, Zhijun; Høiby, Niels
Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs) and pharmacodynamics (PDs) of antimicrobials can reliably be used to predict whether antimicrobial regimens will achieve the maximum bactericidal effect against infections. Unfortunately, however, most PK/PD studies of antimicrobials have been done on planktonic cells and very few PK/PD studies have been done on biofilms, partly due to the lack of suitable models in vivo. In the present study, a biofilm lung infection model was developed to provide an objective and quantitative evaluation of the PK/PD profile of antimicrobials. Killing curves were set up to detect the antimicrobial kinetics on planktonic and biofilm P. aeruginosa cells in vivo. Colistin showed concentration-dependent killing, while imipenem showed time-dependent killing on both planktonic and biofilm P. aeruginosa cells in vivo. The parameter best correlated to the elimination of bacteria in lung by colistin was the area under the curve (AUC) versus MIC (AUC/MIC) for planktonic cells or the AUC versus minimal biofilm inhibitory concentration (MBIC; AUC/MBIC) for biofilm cells. The best-correlated parameter for imipenem was the time that the drug concentration was above the MIC for planktonic cells (TMIC) or time that the drug concentration was above the MBIC (TMBIC) for biofilm cells. However, the AUC/MIC of imipenem showed a better correlation with the efficacy of imipenem for biofilm infections (R2 = 0.89) than planktonic cell infections (R2 = 0.38). The postantibiotic effect (PAE) of colistin and imipenem was shorter in biofilm infections than planktonic cell infections in this model. PMID:22354300
Arduino, Sonia M; Quiroga, María Paula; Ramírez, María Soledad; Merkier, Andrea Karina; Errecalde, Laura; Di Martino, Ana; Smayevsky, Jorgelina; Kaufman, Sara; Centrón, Daniela
Multiple transposons, integrons and carbapenemases were found in Klebsiella pneumoniae colistin-resistant isolates as well as a genomic resistance island of the AbaR type in Acinetobacter baumannii colistin-resistant isolates from different hospitals from Buenos Aires City. PFGE analysis showed a polyclonal dissemination of antimicrobial resistance mechanisms among K. pneumoniae isolates, while in A. baumannii isolates the epidemic clone 1 from South America was found. Resistance determinants associated with horizontal gene transfer are contributing to the evolution to pandrug resistance in both epidemic and sporadic clones.
Full Text Available Abstract Background Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB strains. Methods Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST12 h in a time-kill study. Results The time-kill studies indicated that the minimum inhibitory concentration (MIC of colistin (0.5 or 0.25 μg/mL completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL, minocycline (1 μg/mL or rifampicin (0.06 μg/mL did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL with minocycline (0.5×MIC, 4 or 2 μg/mL was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations were significantly shorter than those of the single drugs (p Conclusions This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.
Micheline A. H. Soudeiha
Full Text Available The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of blaOXA−51−like. Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR–typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI, which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored blaOXA−23−like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem (p < 0.05. The colistin-meropenem and
Soudeiha, Micheline A H; Dahdouh, Elias A; Azar, Eid; Sarkis, Dolla K; Daoud, Ziad
The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB) calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of bla OXA-51-like . Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR-typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI), which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored bla OXA-23-like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem ( p carbapenems could be a promising antimicrobial strategy in
Mohamed, Ami F; Karaiskos, Ilias; Plachouras, Diamantis; Karvanen, Matti; Pontikis, Konstantinos; Jansson, Britt; Papadomichelakis, Evangelos; Antoniadou, Anastasia; Giamarellou, Helen; Armaganidis, Apostolos; Cars, Otto; Friberg, Lena E
A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.
Yassin, Afrah Kamal; Zhang, Jilei; Wang, Jiawei; Chen, Li; Kelly, Patrick; Butaye, Patrick; Lu, Guangwu; Gong, Jiansen; Li, Min; Wei, Lanjing; Wang, Yaoyao; Qi, Kezong; Han, Xiangan; Price, Stuart; Hathcock, Terri; Wang, Chengming
Antimicrobial resistance to colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of multidrug-resistant Enterobacteriaceae infection in humans. In this study, we investigated the presence of colistin resistance genes (mcr-1, mcr-2, mcr-3) in Escherichia coli strains isolated from poultry and livestock collected between 2004 and 2012 in China. Furthermore, we studied the maintenance and transfer of the mcr-1 gene in E. coli after serial passages. Overall, 2.7% (17/624) of the E. coli isolates were positive for the mcr-1 gene while none were positive for the mcr-2 and mcr-3 genes. The prevalences of mcr-1 were similar in E. coli isolates from chickens (3.2%; 13/404), pigs (0.9%; 1/113) and ducks (6.8%; 3/44) but were absent in isolates from cattle (0/63). The mcr-1 gene was maintained in the E. coli after six passages (equivalent to 60 generations). In vitro transfer of mcr-1 was evident even without colistin selection. Our data indicate the presence of mcr-1 in extraintestinal E. coli from food-producing animals in China, and suggest that high numbers of the mcr-1-positive bacteria in poultry and livestock do not appear to be readily lost after withdrawal of colistin as a food additive. © FEMS 2017. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Moskowitz, Samuel M; Brannon, Mark K; Dasgupta, Nandini
Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates...
Gill, M. M.; Usman, J.; Hassan, A.; Kaleem, F.; Anjum, R.
Objective:To compare the in vitroefficacy of meropenem, colistin and tigecycline against extended spectrum Betalactamase producing Gram negative bacilli by minimal inhibitory concentration. Study Design:Cross-sectional descriptive study. Place and Duration of Study: Department of Microbiology, Army Medical College, National University of Sciences and Technology, Rawalpindi, from June to December 2010. Methodology: Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to species level. Extended spectrum beta-lactamase producing Gram negative bacilli were detected by Jarlier disc synergy method and confirmed by ceftazidime and ceftazidime-clavulanate Etest. Minimum Inhibitory Concentration (MIC90) of meropenem, colistin and tigecycline was determined by Etest (AB BIOMERIUX) and the results were interpreted according to the manufacturer's instructions and Clinical and Laboratory Standards Institute guidelines and Food and Drug Authority recommendations. Results were analyzed by using Statistical Package for the Social Sciences version 20. Results: A total of 52 non-duplicate extended spectrum Beta-lactamase-producing Gram negative bacilli were included in the study. The MIC90 of tigecycline (0.75 micro g/ml) was lowest as compared to the meropenem (2 micro g/ml) and colistin (3 micro g/ml). Conclusion: Tigecycline is superior in efficacy against the extended spectrum Beta-lactamase producing Gram negative bacilli as compared to colistin and meropenem. (author)
Full Text Available Treatment of Acinetobacter baumannii meningitis is an important challenge due to the accumulation of resistance of this bacteria and low meningeal diffusion of several antimicrobial requiring use of an antimicrobial effective combination to eradicate these species. We report a case of Acinetobacter baumannii multidrug-resistant nosocomial meningitis which was successfully treated with intravenous and intrathecal colistin associated with rifampicin.
de Knegt, Gerjo J; van der Meijden, Aart; de Vogel, Corné P; Aarnoutse, Rob E; de Steenwinkel, Jurriaan E M
Current treatment for tuberculosis (TB) is complicated by the emergence of multidrug resistant TB (MDR-TB). As a result, there is an urgent need for new powerful anti-TB regimens and novel strategies. In this study, we aimed to potentiate a moxifloxacin + linezolid backbone as treatment for MDR-TB with the efflux pump inhibitors verapamil and timcodar as well as with drugs that act on mycobacterial cell wall stability such as colistin and SQ109. Using a time-kill kinetics assay, the activities of moxifloxacin, linezolid, verapamil, timcodar, colistin and SQ109 as single drugs against Mycobacterium tuberculosis were evaluated. In addition, the activity of the moxifloxacin + linezolid backbone in combination with one of the potentiator drugs was assessed. As little as 0.125 mg/L moxifloxacin achieved 99% killing of M. tuberculosis after 6 days of exposure. Linezolid showed moderate killing but 99% killing was not achieved. Verapamil, timcodar and colistin only resulted in killing with the highest concentrations tested but 99% killing was not achieved. SQ109 resulted in complete elimination after 1 day of exposure to 256 mg/L and in 99% elimination after 6 days of exposure to 1 mg/L. Furthermore, colistin added to the moxifloxacin + linezolid backbone resulted in increased elimination, whereas verapamil, timcodar and SQ109 showed no added value to the backbone. This finding that colistin potentiates the activity of the moxifloxacin + linezolid backbone against M. tuberculosis suggests its potential role in further studies on the applicability of a moxifloxacin + linezolid treatment of MDR-TB. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Merkier, Andrea Karina; Rodríguez, María Cecilia; Togneri, Ana; Brengi, Silvina; Osuna, Carolina; Pichel, Mariana; Cassini, Marcelo H; Centrón, Daniela
Serratia marcescens causes health care-associated infections with important morbidity and mortality. Particularly, outbreaks produced by multidrug-resistant isolates of this species, which is already naturally resistant to several antibiotics, including colistin, are usually described with high rates of fatal outcomes throughout the world. Thus, it is important to survey factors associated with increasing frequency and/or emergence of multidrug-resistant S. marcescens nosocomial infections. We report the investigation and control of an outbreak with 40% mortality due to multidrug-resistant S. marcescens infections that happened from November 2007 to April 2008 after treatment with colistin for Acinetobacter baumannii meningitis was started at hospital H1 in 2005. Since that year, the epidemiological pattern of frequently recovered species has changed, with an increase of S. marcescens and Proteus mirabilis infections in 2006 in concordance with a significant decrease of the numbers of P. aeruginosa and A. baumannii isolates. A single pulsed-field gel electrophoresis (PFGE) cluster of S. marcescens isolates was identified during the outbreak. When this cluster was compared with S. marcescens strains (n = 21) from 10 other hospitals (1997 to 2010), it was also identified in both sporadic and outbreak isolates circulating in 4 hospitals in Argentina. In132::ISCR1::blaCTX-M-2 was associated with the multidrug-resistant cluster with epidemic behavior when isolated from outbreaks. Standard infection control interventions interrupted transmission of this cluster even when treatment with colistin continued in several wards of hospital H1 until now. Optimizing use of colistin should be achieved simultaneously with improved infection control to prevent the emergence of species naturally resistant to colistin, such as S. marcescens and P. mirabilis.
Wei, Pengcheng; Song, Guangji; Shi, Mengyang; Zhou, Yafei; Liu, Yang; Lei, Jun; Chen, Peng; Yin, Lei
Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable mobilized colistin-resistance gene ( mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.
Haagensen, Janus Anders Juul; Klausen, M; Ernst, RK
During Pseudomonas aeruginosa flow cell biofilm development, the cell population differentiates into a nonmotile subpopulation which forms microcolonies and a migrating subpopulation which eventually colonizes the top of the microcolonies, resulting in the development of mushroom-shaped multicell......During Pseudomonas aeruginosa flow cell biofilm development, the cell population differentiates into a nonmotile subpopulation which forms microcolonies and a migrating subpopulation which eventually colonizes the top of the microcolonies, resulting in the development of mushroom......-targeting antibacterial agents. All biofilm-associated cells were sensitive to the antibacterial agents when tested in standard plate assays. A mutation eliminating the production of type IV pili, and hence surface-associated motility, prevented the formation of regular mushroom-shaped structures in the flow cell...... that only the cap-forming subpopulation in biofilms treated with colistin expresses the pmr operon. These results suggest that increased antibiotic tolerance in biofilms may be a consequence of differentiation into distinct subpopulations with different phenotypic properties....
Mavroidi, Angeliki; Likousi, Sofia; Palla, Eleftheria; Katsiari, Maria; Roussou, Zoi; Maguina, Asimina; Platsouka, Evangelia D
An alarming increase in the resistance rates of tigecycline and colistin among carbapenemase-producing Acinetobacter baumannii recovered from a Greek hospital over a 3-year period (2011-2013) was investigated. The antimicrobial resistance profiles and carbapenemase gene content were determined for a collection of colistin- and/or tigecycline-resistant carbapenemase-producing A. baumannii isolates (n = 42), which were recovered consecutively during the study period. A gradual increase in the incidence of blaOXA-23 producers was observed from 2011 to 2013. A cluster of 21 isolates comprised tigecycline-resistant blaOXA-23 producers displayed a single antimicrobial resistance pattern. The emergence of two blaOXA-23 producers resistant to both tigecycline and colistin was documented. Furthermore, determination of the mechanisms of colistin and tigecycline resistance and molecular typing by the tri-locus sequence typing (3LST) scheme for nine isolates recovered from bloodstream infections were performed. Out of nine isolates, five tigecycline- and two colistin-resistant isolates were blaOXA-23 producers of 3LST ST101 corresponding to the international clone II recovered during 2012-2013. All nine isolates were positive for the presence of the adeB gene of the AdeABC efflux pump. Three colistin-resistant isolates possessed novel substitutions in PmrB, which may be implicated in colistin resistance. To the best of our knowledge, this is the first report of the acquisition of tigecycline and colistin resistance among blaOXA-23-producing A. baumannii of 3LST ST101 in Greece; thus, continuous surveillance and molecular characterization, prudent use of antibiotics and implementation of infection control measures for A. baumannii are urgent.
Nakayama, Tatsuya; Jinnai, Michio; Kawahara, Ryuji; Diep, Khong Thi; Thang, Nguyen Nam; Hoa, Tran Thi; Hanh, Le Kieu; Khai, Pham Ngoc; Sumimura, Yoshinori; Yamamoto, Yoshimasa
Reports of livestock infections with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E) are increasing. Based on interviews conducted over a 6-month period, we found that veterinarians in the Vietnamese province of Thai Binh prefer to prescribe colistin-based drugs (CBD) in chicken farms. We aimed to clarify whether CBD use selects for strains of colistin-resistant ESBL-E. With the cooperation of seven local households, we detected ESBL-E in chickens' feces after treating chickens with CBD. Phylogenetic groupings and the presence of CTX-M/AmpC genes were determined, and the multi-antibiotic susceptibility of isolates was analyzed. Our results showed that ESBL-E presented in seven chickens' feces from two households. Seventy-two percent of ESBL-E isolates harbored CTX-M9 and the phylogenetic group A; the colistin minimum inhibitory concentration (MIC) of all isolated ESBL-E ranged from 0.064 to 1 μg mL -1 . Moreover, ESBL-E isolates were used to experimentally select for colistin resistance, and the effect of commercial CBD on ESBL-E was investigated. The results showed that an ESBL-E strain with a colistin MIC of 4 μg mL -1 was able to grow in media with CBD. Although CBD treatment was effective, in vitro experiments demonstrated that ESBL-E can easily acquire colistin resistance. Therefore, restrictions on colistin use are necessary to prevent the emergence of colistin-resistant bacteria.
Le Devendec, Laetitia; Mourand, Gwenaelle; Bougeard, Stéphanie; Léaustic, Julien; Jouy, Eric; Keita, Alassane; Couet, William; Rousset, Nathalie; Kempf, Isabelle
The application of manure may result in contamination of the environment with antimicrobials, antimicrobial-resistant bacteria, resistance genes and plasmids. The aim of this study was to investigate the impact of the administration of colistin and of manure management on (i) the presence of colistin-resistant Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and (ii) the prevalence of various antimicrobial resistance genes in feces and in composted or stored manure. One flock of chickens was treated with colistin at the recommended dosage and a second flock was kept as an untreated control. Samples of feces, litter and stored or composted manure from both flocks were collected for isolation and determination of the colistin-susceptibility of E. coli, K. pneumoniae and P. aeruginosa and quantification of genes coding for resistance to different antimicrobials. The persistence of plasmids in stored or composted manure from colistin-treated broilers was also evaluated by plasmid capturing experiments. Results revealed that colistin administration to chickens had no apparent impact on the antimicrobial resistance of the dominant Enterobacteriaceae and P. aeruginosa populations in the chicken gut. Composting stimulated an apparently limited decrease in genes coding for resistance to different antimicrobial families. Importantly, it was shown that even after six weeks of composting or storage, plasmids carrying antimicrobial resistance genes could still be transferred to a recipient E. coli. In conclusion, composting is insufficient to completely eliminate the risk of spreading antimicrobial resistance through chicken manure. Copyright © 2015 Elsevier B.V. All rights reserved.
Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V
Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.
Tacão, Marta; Tavares, Rafael Dos Santos; Teixeira, Pedro; Roxo, Inês; Ramalheira, Elmano; Ferreira, Sónia; Henriques, Isabel
Escherichia coli Ec36 was recovered from a patient in Portugal after treatment with meropenem and colistin. Besides an IncF plasmid with Tn1441d-bla KPC-3 , already reported in clinical strains in this country, E. coli Ec36 co-harbored an IncX4::mcr-1 gene. Results highlight emerging co-resistance to carbapenems and polymyxins after therapy with drugs from both classes.
Iyad M Ghonimat
Full Text Available Nebulized colistin (NC is used for the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria. In this one-year case-control study, our objective was to evaluate the effect of NC on the ventilator circuit (VC components. The case group consisted of 25 mechanically-ventilated patients who received NC, while the control group was 25 mechanically-ventilated patients who did not receive NC. Respiratory therapists inspected the VC every 4 hrs and whenever a ventilator alarm was reported. The VC component was changed if the alarm did not subside after necessary measures were performed. Patients from both groups were treated at the adult ICU in King Hussein Cancer Center (KHCC. In the case group, 22(88% patients required changing at least one of the circuit components (flow sensor, exhalation membrane, or nebulizer kit. The median number of changes (range per patient of the flow sensor, exhalation membrane, and nebulizer kit were: 2(1-3, 2(1-6, and 1(1-2, respectively. Large amounts of white crystals, which resembled the colistin powder, were reported on the replaced VC components. The flow sensor was changed in 2 control patients, but white crystals were absent. Crystals obtained from one case subject were confirmed to be colistin by chromatographic mass spectroscopy. Further studies are needed to evaluate the effect of crystal formation on the efficacy of NC and clinical outcomes.
Sepahvand, Shahriar; Doudi, Monir; Davarpanah, Mohammad Ali; Bahador, Abbas; Ahmadi, Mehranoosh
Acinetobacter baumanni is known as a worldwide emerging nosocomial infections and it is classified as one of the six dangerous microorganisms by Diseases Society of America. Multi drug-resistant strains of A. baumannii have been reported in recent decades, which may be a result of the high use of antimicrobial agents. Colistin is the last form of treatment against this organism. The presence of pmrA and pmrB genes in A. baumannii causes the resistance of this organism against Colistin. This cross-sectional study was performed on 100 samples of A. baumannii isolated from ulcer, urinary, respiratory, blood of patients admitted to the intensive care unit of Shahid Rajai Shiraz hospital within a 12-month period. The diagnosis was performed by microscopic and biochemical testing using microgen kits. Determining Colistin resistance was carried out by Diffusion Disc, Colistin antibiotic disc of MAST- England and E-test. The analysis of genes pmrA and pmrB genes was done by PCR. 100 A. baumannii samples were diagnosed out of which using diffusion disk 94 cases were sensitive to Colistin and 6 cases were resistant to it. The E-test results in resistant samples presented an MIC equal to 64 micrograms per milliliter. The PCR results in sensitive and resistant to Colistin samples presented the existence of pmrA and pmrB genes. The results indicated the presence of pmrA and pmrB genes that are the main reason of A. baumannii resistance against the last line of treatment of this organism to Colistin.
Asinamai Athliamai Bitrus
Full Text Available Antimicrobial resistance as a result of emergence of extended-spectrum beta lactamase producing Enterobacteriaceae is a major health problem of human and animal that requires an intensive global attention. The production of beta lactamase enzymes remains as one of the major factors contributing to the development of resistance to beta lactams. These enzymes hydrolyze the beta lactam ring of the antibiotic and render it ineffective. Extended-spectrum beta lactamase producing bacteria have the ability to develop resistance to a number of antibiotics including the carbapenem and other third generation cephalosporins. In addition, the recent emergence and dissemination of the colistin resistance determinants mcr-1, mcr-2 and mcr-3 poses a serious threat to colistin as a drug of last resort in human medicine. In this review, we utilized words such as colistin resistance and Escherichia coli, Klebsiella and colistin resistance, colistin resistance and Salmonella as well as detection of mcr-1 genes in Salmonella and E. coli. The extended-spectrum beta lactamase producing bacteria under Enterobacteriaceae that are resistant to colistin possess the ability to be transferred resistant determinants to other susceptible cells at a higher frequency. In this paper, the role of manure from food animals and how air travel contributes to the dissemination of mcr-1 haboring bacteria, resistance determinants and other metabolites that constitute a public health problem was also reviewed. It is concluded that these pathogens have significant consequences to the control of infection and plays key roles in treatment failure with colistin. [J Adv Vet Anim Res 2018; 5(1.000: 1-11
Full Text Available Antibiotic failure is occurring worldwide. In a routine surveillance study on antibioticresistance genes (ARGs in natural water bodies, we noted the detection of colistin-resistance gene mcr-1, previously identified in Escherichia coli and Klebsiella pneumoniae isolates from human beings and animals in several countries. The mcr-1 gene might be present in water environments, because aquatic ecosystems are recognized as reservoirs for antibiotic resistant bacteria (ARB and ARGs. In this study, a qPCR assay was developed to monitor and quantify the mcr-1 gene in the Haihe River, China. The results showed that all 18 samples collected from different locations over 6 months along the Haihe River were positive for the mcr-1 gene, and the highest level of mcr-1 reached 3.81 × 105 gene copies (GC per liter of water. This is the first study to quantify mcr-1 in a natural water system by qPCR. Our findings highlight the potential for this antibiotic resistance determinant to spread extensively, suggesting a significant health and ecological impact.
Wang, Wenbo; Zhou, Qi Tony; Sun, Si-Ping
is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell......, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither...
Beyrouthy, Racha; Robin, Frederic; Lessene, Aude; Lacombat, Igor; Dortet, Laurent; Naas, Thierry; Ponties, Valérie; Bonnet, Richard
The spread of mcr-1 -encoding plasmids into carbapenem-resistant Enterobacteriaceae raises concerns about the emergence of untreatable bacteria. We report the acquisition of mcr-1 in a carbapenem-resistant Escherichia coli strain after a 3-week course of colistin in a patient repatriated to France from Portugal. Whole-genome sequencing revealed that the Klebsiella pneumoniae carbapenemase-producing E. coli strain acquired two plasmids, an IncL OXA-48-encoding plasmid and an IncX4 mcr-1 -encoding plasmid. This is the first report of mcr-1 in carbapenemase-encoding bacteria in France. Copyright © 2017 American Society for Microbiology.
Mediavilla, José R; Patrawalla, Amee; Chen, Liang; Chavda, Kalyan D; Mathema, Barun; Vinnard, Christopher; Dever, Lisa L; Kreiswirth, Barry N
Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of
Hermansen, Grith Miriam Maigaard; Jelsbak, Lars
Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have...... inhibitory concentration by microbroth dilution, virulence in an amoebae model and LPS structure by visualization in a silver-stained gel. Results: Reversion of the SNP to reference genotype resulted in increased colistin susceptibility, reduced virulence in an amoebae model and altered LPS structure...
Hernández, Marta; Iglesias, M Rocío; Rodríguez-Lázaro, David; Gallardo, Alejandro; Quijada, Narciso; Miguela-Villoldo, Pedro; Campos, Maria Jorge; Píriz, Segundo; López-Orozco, Gema; de Frutos, Cristina; Sáez, José Luis; Ugarte-Ruiz, María; Domínguez, Lucas; Quesada, Alberto
Colistin resistance genes mcr-3 and mcr-1 have been detected in an Escherichia coli isolate from cattle faeces in a Spanish slaughterhouse in 2015. The sequences of both genes hybridised to same plasmid band of ca 250 kb, although colistin resistance was non-mobilisable. The isolate was producing extended-spectrum beta-lactamases and belonged to serotype O9:H10 and sequence type ST533. Here we report an mcr-3 gene detected in Europe following earlier reports from Asia and the United States. This article is copyright of The Authors, 2017.
Full Text Available BACKGROUND: Resistance to antibiotics among Enterobacteriacae represents a serious therapeutic and infection control challenge. The objective of this study was to determine the frequency of carbapenem, colistin and tigecycline resistant Enterobacteriaceae isolates obtained from patients admitted in medical intensive care unit (ICU of a tertiary care hospital in Karachi, Pakistan. METHODS: This was a descriptive cross sectional study that was conducted at Liaquat National Postgraduate Medical Centre, Karachi, Pakistan during December 2015 to May 2016. Patients admitted in the medical ICU with systemic inflammatory response syndrome were included. The culture positive samples were analyzed for further identification and antimicrobial sensitivity was performed according to clinical laboratory standard institute (CLSI 2014 guidelines. RESULTS: Of the 748 samples, 177 were positive for Enterobactericae. Most samples were taken from blood 75(42.2% or tracheal secretions 67(37.9%. Most common organism isolated were Klebsiella pneumoniae 77(43.5% and Escherichia coli 71(40.1%. Out of these 10.7% organisms were resistant to meropenem, while 2.8% and 20.3% were resistant to colistin and tigecycline respectively. CONCLUSION: Increasing spread of drug resistance among Enterobacteriacae reflects an important problem that can be controlled with effective policies of infection control, surveillance and antimicrobial stewardship.
Singkham-In, Uthaibhorn; Chatsuwan, Tanittha
Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem. Copyright © 2018. Published by Elsevier Inc.
Full Text Available We investigated the synergism of colistin and imipenem against a multidrug-resistant K. pneumoniae isolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the common β-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. The blaSHV-31, blaCMY-2, and blaDHA-1 were detected. Outer membrane porin genes analysis revealed loss of ompK36 and frame-shift mutation of ompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L and 1x MIC of imipenem (8 mg/L was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistant K. pneumoniae infections.
Conclusion: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.
Hasman, H.; Hammerum, A. M.; Hansen, F.
The plasmid-mediated colistin resistance gene, mcr-1, was detected in an Escherichia coli isolate from a Danish patient with bloodstream infection and in five E. coli isolates from imported chicken meat. One isolate from chicken meat belonged to the epidemic spreading sequence type ST131...
Leu, Hsieh-Shong; Ye, Jung-Jr; Lee, Ming-Hsun; Su, Lin-Hui; Huang, Po-Yen; Wu, Tsu-Lan; Huang, Ching-Tai
The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates. Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction. A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively. The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice. Copyright © 2013. Published by Elsevier B.V.
Simonetti, Oriana; Cirioni, Oscar; Ghiselli, Roberto; Orlando, Fiorenza; Silvestri, Carmela; Mazzocato, Susanna; Kamysz, Wojciech; Kamysz, Elzbieta; Provinciali, Mauro; Giacometti, Andrea; Guerrieri, Mario; Offidani, Annamaria
The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections. Copyright © 2014 Elsevier Inc. All rights reserved.
Full Text Available Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum Î²-lactamase (ESBL-producing Klebsiella pneumoniae (KP clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: InÂ vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5Â ÃÂ 105Â CFU/mL by using 1/2Ã MIC for each alone, and both 1/2Ã and 1/4Ã MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2Ã MIC and 1/4Ã MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2Ã MIC and 1/4Ã MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline
Moubareck, Carole Ayoub; Mouftah, Shaimaa F; Pál, Tibor; Ghazawi, Akela; Halat, Dalal H; Nabi, Anju; AlSharhan, Mouza A; AlDeesi, Zulfa O; Peters, Christabel C; Celiloglu, Handan; Sannegowda, Manjunath; Sarkis, Dolla K; Sonnevend, Ágnes
Few studies have addressed the molecular epidemiology of carbapenem resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 - June 2016 were determined. Thirty three percent of the collection of 70 K. pneumoniae, 13 E. coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (four K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM, and 22.1% both OXA-48-like and NDM, respectively. PFGE clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention. Copyright © 2018. Published by Elsevier B.V.
Nguyen, Nhung T; Nguyen, Hoa M; Nguyen, Cuong V; Nguyen, Trung V; Nguyen, Men T; Thai, Hieu Q; Ho, Mai H; Thwaites, Guy; Ngo, Hoa T; Baker, Stephen; Carrique-Mas, Juan
Antimicrobial resistance (AMR) is a global health problem, and emerging semi-intensive farming systems in Southeast Asia are major contributors to the AMR burden. We accessed 12 pig and chicken farms at key stages of production in Tien Giang Province, Vietnam, to measure antimicrobial usage and to investigate the prevalence of AMR to five critical antimicrobials (β-lactams, third-generation cephalosporins, quinolones, aminoglycosides, and polymyxins) and their corresponding molecular mechanisms among 180 Escherichia coli isolates. Overall, 94.7 mg (interquartile range [IQR], 65.3 to 151.1) and 563.6 mg (IQR, 398.9 to 943.6) of antimicrobials was used to produce 1 kg (live weight) of chicken and pig, respectively. A median of 3 (out of 8) critical antimicrobials were used on pig farms. E. coli isolates exhibited a high prevalence of resistance to ampicillin (97.8% and 94.4% for chickens and pigs, respectively), ciprofloxacin (73.3% and 21.1%), gentamicin (42.2% and 35.6%), and colistin (22.2% and 24.4%). The prevalence of a recently discovered colistin resistance gene, mcr-1, was 19 to 22% and had strong agreement with phenotypic colistin resistance. We conducted plasmid conjugation experiments with 37 mcr-1 gene-positive E. coli isolates and successfully observed transfer of the gene in 54.0% of isolates through a plasmid of approximately 63 kb, consistent with one recently identified in China. We found no significant correlation between total use of antimicrobials at the farm level and AMR. These data provide additional insight into the role of mcr-1 in colistin resistance on farms and outline the dynamics of phenotypic and genotypic AMR in semi-intensive farming systems in Vietnam. Our study provides accurate baseline information on levels of antimicrobial use, as well as on the dynamics of phenotypic and genotypic resistance for antimicrobials of critical importance among E. coli over the different stages of production in emerging pig and poultry production
Full Text Available The aim of the study was to develop a multiplex assay for rapid detection of mcr-1, mcr-2, and mcr-3, a group of genes of conferring resistance to colistin mediated by plasmid in Enterobacteriaceae. A SYBR Green based real-time PCR assay has been designed to detect the mcr genes, and applied to cultured bacteria, feces and soil samples. All three mcr genes could be detected with a lower limit of 102 cultured bacteria. This test was highly specific and sensitive, and generated no false-positive results. The assay was also conclusive when applied to feces and soil samples containing mcr-1-positive Escherichia coli, which could facilitate the screening of mcr genes not only in the bacteria, but also directly from the environment. This simple, rapid, sensitive, and specific multiplex assay will be useful for rapid screening of the colistin resistance in both clinical medicine and animal husbandry.
Le Minh, Vien; Thi Khanh Nhu, Nguyen; Vinh Phat, Voong; Thompson, Corinne; Huong Lan, Nguyen Phu; Thieu Nga, Tran Vu; Thanh Tam, Pham Thi; Tuyen, Ha Thanh; Hoang Nhu, Tran Do; Van Hao, Nguyen; Thi Loan, Huynh; Minh Yen, Lam; Parry, Christopher M; Trung Nghia, Ho Dang; Campbell, James I; Hien, Tran Tinh; Thwaites, Louise; Thwaites, Guy; Van Vinh Chau, Nguyen; Baker, Stephen
Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.
Abdul Momin, Muhd Haziq F; Bean, David C; Hendriksen, Rene S.
Purpose. A selective chromogenic culture medium for the laboratory isolation and differentiation of colistin resistant Acinetobacter, Pseudomonas, Stenotrophomonas and Enterobacteriaceae spp. (CHROMagar COL-APSE) was developed, evaluated and compared to an existing selective bacterial culture......-resistant non-fermentative bacteria (Acinetobacter, Pseudomonas and Stenotrophomonas). CHROMagar COL-APSE was also more sensitive in supporting the growth of Enterobacteriaceae with COL resistance associated with the carriage of mcr-1. Conclusion. CHROMagar COL-APSE is a sensitive and specific medium...
José R. Mediavilla
Full Text Available Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.
Ribera, Alba; Benavent, Eva; Lora-Tamayo, Jaime; Tubau, Fe; Pedrero, Salvador; Cabo, Xavier; Ariza, Javier; Murillo, Oscar
In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular infections (OIs) add more difficulties to its treatment. The role of β-lactams (BLs) is questioned and older drugs need to be reconsidered. The objective of this study was to describe our experience in the management of OIs caused by MDR P. aeruginosa and evaluate different therapeutic options. This was a retrospective analysis of a prospectively collected cohort (2004-13) of patients with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA) managed with device retention; and (ii) Group B (less difficult to treat), OA managed without device retention. Antibiotic treatment was administered according to clinician criteria: monotherapy/combined therapy; and BL used by intermittent bolus (IB)/continuous infusion. Of 34 patients, 15 (44.1%) had PJI and 19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%) were caused by XDR P. aeruginosa. The initial management included removal of an orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4 colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%; 5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and 63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to 73.3% with combined therapy (P = 0.016), with special interest within Group A (cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which included removal of remaining devices, the cure rate reached 85.3%. We suggest that the BL/colistin combination is an optimized therapy for OI caused by MDR P. aeruginosa, together with an appropriate surgical treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: email@example.com.
High-throughput hydrophilic interaction chromatography coupled to tandem mass spectrometry for the optimized quantification of the anti-Gram-negatives antibiotic colistin A/B and its pro-drug colistimethate.
Mercier, Thomas; Tissot, Fréderic; Gardiol, Céline; Corti, Natascia; Wehrli, Stéphane; Guidi, Monia; Csajka, Chantal; Buclin, Thierry; Couet, William; Marchetti, Oscar; Decosterd, Laurent A
Colistin is a last resort's antibacterial treatment in critically ill patients with multi-drug resistant Gram-negative infections. As appropriate colistin exposure is the key for maximizing efficacy while minimizing toxicity, individualized dosing optimization guided by therapeutic drug monitoring is a top clinical priority. Objective of the present work was to develop a rapid and robust HPLC-MS/MS assay for quantification of colistin plasma concentrations. This novel methodology validated according to international standards simultaneously quantifies the microbiologically active compounds colistin A and B, plus the pro-drug colistin methanesulfonate (colistimethate, CMS). 96-well micro-Elution SPE on Oasis Hydrophilic-Lipophilic-Balanced (HLB) followed by direct analysis by Hydrophilic Interaction Liquid Chromatography (HILIC) with Ethylene Bridged Hybrid--BEH--Amide phase column coupled to tandem mass spectrometry allows a high-throughput with no significant matrix effect. The technique is highly sensitive (limit of quantification 0.014 and 0.006 μg/mL for colistin A and B), precise (intra-/inter-assay CV 0.6-8.4%) and accurate (intra-/inter-assay deviation from nominal concentrations -4.4 to +6.3%) over the clinically relevant analytical range 0.05-20 μg/mL. Colistin A and B in plasma and whole blood samples are reliably quantified over 48 h at room temperature and at +4°C (<6% deviation from nominal values) and after three freeze-thaw cycles. Colistimethate acidic hydrolysis (1M H2SO4) to colistin A and B in plasma was completed in vitro after 15 min of sonication while the pro-drug hydrolyzed spontaneously in plasma ex vivo after 4 h at room temperature: this information is of utmost importance for interpretation of analytical results. Quantification is precise and accurate when using serum, citrated or EDTA plasma as biological matrix, while use of heparin plasma is not appropriate. This new analytical technique providing optimized quantification in real
Wei, Wen-Juan; Yang, Hai-Fei
Combination antimicrobial therapy is an important option in the fight against Gram-negative 'superbugs'. This study systematically investigated the synergistic effect of colistin (CST) and chloramphenicol (CHL) in combination against extensively drug-resistant Acinetobacter baumannii (XDR-AB). The microtitre plate chequerboard assay was used to test synergy against 50 XDR-AB clinical strains. Then, three XDR-AB clinical isolates and the type strain A. baumannii ATCC 19606 were chosen for further synergy studies using time-kill assay, mutant prevention concentration (MPC) assay and real-time population analysis profile (PAP) assay. In the chequerboard assays, synergistic or additive effects [defined as a fractional inhibitory concentration index (FICI) of ≤0.5 and 0.5 synergy testing, the results of time-kill assays indicated that CST monotherapy produced rapid bacterial killing followed by rapid re-growth, with the emergence of CST resistance; CHL monotherapy was largely ineffective. The combination CST/CHL, however, showed a synergistic effect and enhanced bacterial killing in the four tested strains. It also significantly delayed re-growth and suppressed the emergence of CST resistance. In the MPC assay, a decrease in MPCs for CST was observed in the two CST-susceptible strains. PAP assay showed that both CST-resistant strains were heteroresistant. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Spiliopoulou, Anastasia; Jelastopulu, Eleni; Vamvakopoulou, Sofia; Bartzavali, Christina; Kolonitsiou, Fevronia; Anastassiou, Evangelos D; Christofidou, Myrto
Acinetobacter baumannii has emerged as an important and problematic pathogen causing bloodstream infections (BSI) in hospitalized patients. Results of an 8-year period from a university hospital are presented. Identification of A. baumannii was performed by Gram-negative BD BBL Crystal ID and VITEK(®)2 system, whereas, susceptibility testing by VITEK2, Kirby-Bauer disc system, and Etest strips. Interpretation of results was based on CLSI criteria and, regarding tigecycline, Food and Drug Administration (FDA) criteria. Between 2006 and 2013, 441 among 7088 BSI cases were attributed to A. baumannii. Of all isolates, 92·1% were resistant to more than three classes of antibiotics and 79·4% were resistant to all but one or two categories of antimicrobials. Resistance to ampicillin-sulbactam, meropenem, gentamicin, ciprofloxacin, minocycline, and tigecycline increased during the study period (P<0·05). Although tigecycline resistance was low during the first 4 years of the study (25·5%), it increased up to 66·5% during 2010-2013. No isolate was colistin resistant.
Full Text Available Acinetobacter baumanni is an important nosocomial infection pathogen has emerged worldwide and can causes life-threatening hospital acquired infections, particularly in intensive care units (ICU. After post neurosurgical operations or procedures, this pathogen consists with central nervous system (CNS infections, also. Resistance mechanism of these pathogens against broad-spectrum antimicrobials is the challenging problem and limited penetration of antibiotics to achieve therapeutic concentrations in cerebrospinal fluid (CSF has been still controversial issue. Here we report two cases who had ventriculitis after external ventricular drainage (EVD placement procedures. Both of CSF of two cases yielded XDR (Extensively drug resistant Acinetobacter baumanni. Traditional intravenous treatment did not eradicate pathogen exactly, at first. Adjunctive colistimetat sodium every 12 h (10 mg/kg/day by the route of intraventriculer (IVT was admitted and CSF sterilization was achieved thereafter. The option of IVT colistin administration must be considered with IV antibiotherapy to provide satisfactory treatment of those complicated CNS infections. [Dis Mol Med 2014; 2(4.000: 65-69
Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii.
Luque, Sònia; Grau, Santiago; Valle, Marta; Sorlí, Luisa; Horcajada, Juan Pablo; Segura, Concha; Alvarez-Lerma, Francisco
Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Abdul Momin, Muhd Haziq F; Bean, David C; Hendriksen, Rene S.
medium (SuperPolymyxin). Methodology. The medium was challenged with 84 isolates, including polymyxin B (POL B)-susceptible and -resistant type strains and colistin (COL)-resistant organisms recovered from human and animal samples. Susceptibility to COL and POL B was determined by agar dilution and broth...... microtitre dilution. The lower limit for the detection of COL-resistant organisms was also calculated for both CHROMagar COL-APSE and SuperPolymyxin media. The ability to isolate and correctly differentiate COL-resistant organisms within mixed cultures was also assessed and compared using both media. Results...
Yen, Hung-Che; Lai, Wei-Kang; Lin, Chuan-Shun; Chiang, Shu-Hsing
Five hundred and twenty-eight newly weaned pigs were given four treatments, with eight replicates per treatment. Sixteen to 18 pigs were assigned per replicate and were fed diets supplemented with 0 or 3% medium-chain triglyceride (MCT) and 0 or 40 ppm colistin sulfate (CS) in a 2 × 2 factorial arrangement for 2 weeks. The results showed that dietary supplementation with MCT improved the gain-to-feed ratio during days 3-7 and in the overall period (P environment and the feed utilization efficiency of newly weaned pigs. © 2014 Japanese Society of Animal Science.
Wei, Wenjuan; Yang, Haifei; Hu, Lifen; Ye, Ying; Li, Jiabin
Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB) and the lack of novel agents. Although recent data suggest that levofloxacin (LVX) may have unique activity against MDR-AB in combination with colistin (CST), further preclinical work is needed. We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115) of MDR-AB to investigate the in vitro and in vivo efficacy of LVX-CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time-kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied in vitro. A simple invertebrate model (Galleria mellonella) has been used to assess the in vivo activity of antimicrobial therapies. The LVX-CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624). In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p < 0.05). In summary, a synergistic or additive effect between CST and LVX was observed in vitro and in vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones. Copyright © 2015. Published by Elsevier B.V.
Full Text Available Seven wastewater treatment plants (WWTPs with different population equivalents and catchment areas were screened for the prevalence of the colistin resistance gene mcr-1 mediating resistance against last resort antibiotic polymyxin E. The abundance of the plasmid-associated mcr-1 gene in total microbial populations during water treatment processes was quantitatively analyzed by qPCR analyses. The presence of the colistin resistance gene was documented for all of the influent wastewater samples of the seven WWTPs. In some cases the mcr-1 resistance gene was also detected in effluent samples of the WWTPs after conventional treatment reaching the aquatic environment. In addition to the occurrence of mcr-1 gene, CTX-M-32, blaTEM, CTX-M, tetM, CMY-2, and ermB genes coding for clinically relevant antibiotic resistances were quantified in higher abundances in all WWTPs effluents. In parallel, the abundances of Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli were quantified via qPCR using specific taxonomic gene markers which were detected in all influent and effluent wastewaters in significant densities. Hence, opportunistic pathogens and clinically relevant antibiotic resistance genes in wastewaters of the analyzed WWTPs bear a risk of dissemination to the aquatic environment. Since many of the antibiotic resistance gene are associated with mobile genetic elements horizontal gene transfer during wastewater treatment can't be excluded.
Li, Yi; Sun, Qiao-Ling; Shen, Yingbo; Zhang, Yangjunna; Yang, Jun-Wen; Shu, Ling-Bin; Zhou, Hong-Wei; Wang, Yang; Wang, Bing; Zhang, Rong; Wang, Shaolin; Shen, Zhangqi
The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital. Copyright © 2018 American Society for Microbiology.
Sherry, Norelle; Howden, Benjamin
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're-discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non-reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.
Bahador, Abbas; Taheri, Mohammad; Pourakbari, Babak; Hashemizadeh, Zahra; Rostami, Hossein; Mansoori, Noormohamad; Raoofian, Reza
Multidrug-resistant Acinetobacter baumannii infections are serious challenges for clinicians because of A. baumannii propensity to acquire resistance to a wide spectrum of antimicrobial agents. In this study, 91 A. baumannii isolates from patients in tertiary intensive care units of three university hospitals in the north, central, and south of Iran were selected and tested for susceptibility to 22 antimicrobials; amplified restriction fragment polymorphism and multiplex polymerase chain reaction methods were used to determine genetic relationships and International Clone (IC) of A. baumannii isolates, respectively. Twenty-four genotypes were identified in A. baumannii isolates. About 91.2% of isolates categorized into 4 distinct clusters; one was more heterogeneous and observed across the three locations. A considerable number of the isolates (27.5%) belonged to the novel IC variant, sequence group 7 (SG7), which was geographically widespread in three locations. The drug resistance pattern showed that 14.2%, 20%, and 77% of the A. baumannii isolates were resistant to colistin, tigecycline, and rifampicin, respectively. Nine percent of isolates (8) showed simultaneous resistance to colistin, rifampicin, and tigecycline. Interestingly, all of them were susceptible to ampicillin-sulbactam and/or tobramycin. According to our results, SG7 could be considered as a pan-Iranian clone.
Full Text Available Antimicrobial research is being pressured to look for more effective therapeutics for the ever-growing antibiotic-resistant infections, and antimicrobial peptides (AMP and antimicrobial combinations are promising solutions. This work evaluates colistin-AMP combinations against two major pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, encompassing non- and resistant strains. Colistin (CST combined with the AMP temporin A (TEMP-A, citropin 1.1 (CIT-1.1 and tachyplesin I linear analogue (TP-I-L was tested against planktonic, single- and double-species biofilm cultures. Overall synergy for planktonic P. aeruginosa and synergy/additiveness for planktonic S. aureus were observed. Biofilm growth prevention was achieved with synergy and additiveness. Pre-established 24 h-old biofilms were harder to eradicate, especially for S. aureus and double-species biofilms; still, some synergy and addictiveness was observed for higher concentrations, including for the biofilms of resistant strains. Different treatment times and growth media did not greatly influence AMP activity. CST revealed low toxicity compared with the other AMP but its combinations were toxic for high concentrations. Overall, combinations reduced effective AMP concentrations, mainly in prevention scenarios. Improvement of effectiveness and toxicity of therapeutic strategies will be further investigated.
Leroy, P; Decolin, D; Nicolas, S; Archimbault, P; Nicolas, A
Residues of two antibacterial agents, cephalexin and colistin, co-administered by intramuscular injection to calves, were quantified in four different tissues (muscle, fat, liver and kidney) by column switching HPLC and by a microbiological method. For cephalexin assay, tissue samples with cephradin as internal standard were homogenized in a 5% trichloroacetic acid solution and filtrates were injected onto a concentration precolumn filled with LiChroprep RP-18 (25-40 microns). A clean-up step was incorporated by flowing a mobile phase (methanol-0.01 M phosphate buffer (pH 3.0); 15:85, v/v) through the enrichment column before elution on a LiChrospher RP-18e (5 microns) column with a methanol-phosphate buffer (30:70, v/v) at a flow rate of 1 ml min-1. Spectrometric detection was at 260 nm. An additional "off-line" washing step of extracts with methylene chloride was operated to achieve higher selectivity in the case of liver and kidney samples. The limit for quantitative assay was 0.045 micrograms g-1 with relative standard deviations in the range 5-8% and recoveries within 70%. For microbiological assay of colistin, samples were homogenized in 0.1 M hydrochloric acid-acetonitrile mixtures (3:1, v/v, for kidney and liver; 3:2, v/v, for fat and muscle). The supernatants were assayed by the cylinder plate method after evaporation to dryness under vacuum. Bordetella bronchiseptica ATCC 4617 was chosen as test organism. After a 3-h diffusion step at room temperature, the medium was incubated at 37 degrees C for 18 h and then the diameter of the growth inhibition zones was measured. Sensitivity reached 0.10-0.15 micrograms g-1. Results from the analysed samples over a 7-28 day period after drug administration show that no cephalexin was found at concentrations higher than the quantitation limit in the four test tissues and that colistin was found in muscle (injection site only) for 15 days and in kidney for 21 days.
Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T
Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.
Haque, Anwarul; Ishii, Yoshikazu; Akasaka, Yoshikiyo; Matsumoto, Tetsuya; Tateda, Kazuhiro
Despite of proven LPS neutralizing activity, intravenous polymyxin use was waned due to experience of associated nephrotoxicity. But, increasing resistance to all available antibiotics has necessitated their resurgence and the prodrug of colistin sulfate (CS), known as colistin-methanesulfonate (CMS), is increasingly used as the only therapeutic option in many infections. Currently available CMS employ very different dose definitions and thus because of complex pharmacokinetics/pharmacodynamics information and short half-life, this drug use remains confusing. We aimed to expose CS in endotoxic shock models by micro-osmotic pump and evaluated its effectiveness. We used micro-osmotic pumps to deliver either sterile saline or CS at different dosages ranging from 0.25mg/day to 7mg/day for consecutive 3days in LPS (8mg/kg body weight) induced endotoxic mice and observed their outcome twice daily for a week to determine the survival rate. Serum pro-inflammatory cytokine levels and apoptosis in renal tissues in these models were evaluated. We showed endotoxic shock was reversed and all mice survived with a CS administration at a dosage of 2mg/day for 3 days, in comparison to survival rate with saline administration (p≤0.0001) in endotoxic models. CS infusion in shock models using micro-osmotic pump ameliorated rising of serum TNF-α, IL-12p70 and IL-6 levels. Nephrotoxicity was evident only with a higher dosage, but not with a lower dosage which was optimum to control endotoxic shock in models. These results highlighted that an optimal dosage of CS effectively improved outcome in endotoxic shock models without causing nephrotoxicity when administered at a slow and sustained manner. And a higher CS dosage administration was nephrotoxic and fatal. Thus this study bought an opportunity to consider future investigations with CS administration in murine Gram-negative bacterial infections in a novel way. Copyright © 2017 International Society for Chemotherapy of Infection
Weterings, V; Zhou, K; Rossen, J W; van Stenis, D; Thewessen, E; Kluytmans, J; Veenemans, J
We describe an outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-KP) ST258 that occurred in two institutions (a hospital and a nursing home) in the Netherlands between July and December 2013. In total, six patients were found to be positive for KPC-KP. All isolates were resistant to colistin and exhibited reduced susceptibility to gentamicin and tigecycline. In all settings, extensive environmental contamination was found. Whole genome sequencing revealed the presence of bla KPC-2 and bla SHV-12 genes, as well as the close relatedness of patient and environmental isolates. In the hospital setting, one transmission was detected, despite contact precautions. After upgrading to strict isolation, no further spread was found. After the transfer of the index patient to a nursing home in the same region, four further transmissions occurred. The outbreak in the nursing home was controlled by transferring all KPC-KP-positive residents to a separate location outside the nursing home, where a dedicated nursing team cared for patients. This outbreak illustrates that the spread of pan-resistant Enterobacteriaceae can be controlled, but may be difficult, particularly in long-term care facilities. It, therefore, poses a major threat to patient safety. Clear guidelines to control reservoirs in and outside the hospitals are urgently needed.
Rhouma, Mohamed; Fairbrother, John Morris; Thériault, William; Beaudry, Francis; Bergeron, Nadia; Laurent-Lewandowski, Sylvette; Letellier, Ann
Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 10 9 CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p F4-positive and F4-negative ETEC in pigs. However, CS clinical efficiency was correlated with non-detection of F4-positive ETEC in the feces. Furthermore the fecal presence of F4-negative ETEC was not associated with clinical symptoms of post-weaning diarrhea in pigs.
Boluki, Ebrahim; Kazemian, Hossein; Peeridogaheh, Hadi; Alikhani, Mohammad Yousef; Shahabi, Sima; Beytollahi, Leili; Ghorbanzadeh, Roghayeh
Nosocomially-acquired multi-, extensively-, and pandrug resistant (MDR, XDR, and PDR) strains of microorganisms such as Acinetobacter baumannii remain a serious cause of infection and septic mortality in burn patients. Treatment of patients with nosocomial burn wound infections is often complicated by drug-resistant strains of A. baumannii. Today, many researchers are focusing on the investigation of novel non-antibiotic strategies such as photodynamic therapy (PDT). We report a new PDT strategy that suppresses colistin resistance in PDR A. baumannii by interfering with the expression of a pmrA/pmrB two-component system. In the current study, A. baumannii with a PDR feature isolated from a burn patient was used as a test strain. PDT was carried out using toluidine blue O (TBO) and light-emitting diode (LED) as a photosensitizer and radiation source, respectively. The antimicrobial susceptibility profiles were assessed for cells surviving PDT. The effects of sub-lethal PDT (sPDT) on the expression of the pmrA/pmrB two-component signal transduction system were evaluated by real-time quantitative reverse transcription PCR. Results of drug susceptibly testing (DST) in LED and TBO groups separately showed that the bacteria were resistant to all tested antibiotics, while the DST result of the LED+TBO group showed highly declining bacterial growth when compared with the control group. Reduction in the expression of pmrA and pmrB was observed in the treated strains after sPDT. This represents the first conclusive example of a direct role for the PDT in breaking antibiotic resistance by directly modulating two-component system activity. Copyright © 2017 Elsevier B.V. All rights reserved.
Lodise, Thomas P; Fan, Weihong; Griffith, David C; Dudley, Michael N; Sulham, Katherine A
Nonclinical studies have suggested that oxidative damage, caspase-mediated apoptosis, and inducible nitric oxide synthase levels may be involved in the pathogenesis of colistin (CST)-associated acute renal failure. MIN inhibits caspase 1, caspase 3, and inducible nitric oxide synthase, leading to the hypothesis that coadministration of CST with MIN (CST-MIN) may reduce the incidence of acute renal failure as well as produce additive or synergistic antimicrobial effects. A multicenter retrospective cohort study was conducted using the Premier Research database to examine the impact of CST-MIN on acute renal failure. Inclusion criteria were as follows: age of ≥18 years, intensive care unit admission at CST initiation, primary International Classification of Diseases 9 (ICD-9) diagnosis of pneumonia or sepsis, nondialysis at hospital admission, and discharge between January 2010 and December 2015. ICD-9 code 584.XX or ICD-10 code N17 was used to define acute renal failure. Baseline comparisons, 1:8 propensity score matching, and confirmatory logistic regression analyses were conducted. In total, 4,817 patients received CST and met inclusion criteria; 93 received CST-MIN. Unadjusted frequency of acute renal failure was significantly lower in patients receiving CST-MIN than CST (11.8% versus 23.7%, P = 0.007). Similar results were seen in propensity score matching (12.0% versus 22.3%, P = 0.031) and logistic regression analyses (odds ratio of 0.403, P = 0.006). Mortalities and 30-day readmission rates were similar between groups. The acute renal failure rate was not impacted by prevalence of baseline renal disease. CST-MIN in critically ill patients may reduce CST-associated acute renal failure. Further evaluation of this combination in prospective clinical studies is warranted. Copyright © 2017 Lodise et al.
Full Text Available Background/Purpose: Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB and the lack of novel agents. Although recent data suggest that levofloxacin (LVX may have unique activity against MDR-AB in combination with colistin (CST, further preclinical work is needed. Methods: We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115 of MDR-AB to investigate the inÂ vitro and inÂ vivo efficacy of LVXâCST combination. Synergy studies were performed using the microtiter plate chequerboard assay and timeâkill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied inÂ vitro. A simple invertebrate model (Galleria mellonella has been used to assess the inÂ vivo activity of antimicrobial therapies. Results: The LVXâCST combination was bactericidal against the CST-susceptible clinical isolate (GN0624. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of < 0.5 was observed between CST and LVX in GN0624. The combination had antibiofilm properties on the preformed biofilms of four tested strains and could prevent the emergence of CST-resistant A. baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (pÂ <Â 0.05. Conclusion: In summary, a synergistic or additive effect between CST and LVX was observed inÂ vitro and inÂ vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones. Keywords: Acinetobacter baumannii, antimicrobial synergy, invertebrate model, levofloxacin, polymyxins
of nosocomial pneumonia and ventilator-associated ... University Medical Faculty Hospital and diagnosed with nosocomial pneumonia/VAP caused by A. baumannii between January. 2009 and ... were to investigate clinical response, bacterial eradication and ... Organ Failure Assessment (SOFA) scores, and the severity of.
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The validation of the analytical method (HPLC, use for identification and assay of the pharmaceutical active ingredient, colistine sulphate and the finished product Colidem 50 – hydrosoluble powder, in SC DELOS impex ‘96 SRL
Full Text Available In SC DELOS IMPEX ’96 SRL the quality of the active pharmaceutical ingredient (API for the finished product Colidem 50 - hydrosoluble powder is make according to European Pharmacopoeia, curent edition. The method for analysis use in this purpose is the compendial method „Colistine sulphate” in E.P. in current edition and represent a optimized variant, developed and validated „in house”.The parameters which was included in the methodology validation for chromatographic method are the follow: Selectivity/Specificity, Linearity, Range of Linearity, Limit of Detection and Limit of Quantification, Precision (Repeatability - intra day, inter-Day Reproducibility, Accuracy, Robustness, Stability Solutions and System Suitability.
Colistin-Resistant, Lipopolysaccharide-Deficient Acinetobacter baumannii Responds to Lipopolysaccharide Loss through Increased Expression of Genes Involved in the Synthesis and Transport of Lipoproteins, Phospholipids, and Poly-β-1,6-N-Acetylglucosamine
Henry, Rebekah; Vithanage, Nuwan; Harrison, Paul; Seemann, Torsten; Coutts, Scott; Moffatt, Jennifer H.; Nation, Roger L.; Li, Jian; Harper, Marina; Adler, Ben
We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971–4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface. PMID:22024825
Colistin-resistant, lipopolysaccharide-deficient Acinetobacter baumannii responds to lipopolysaccharide loss through increased expression of genes involved in the synthesis and transport of lipoproteins, phospholipids, and poly-β-1,6-N-acetylglucosamine.
Henry, Rebekah; Vithanage, Nuwan; Harrison, Paul; Seemann, Torsten; Coutts, Scott; Moffatt, Jennifer H; Nation, Roger L; Li, Jian; Harper, Marina; Adler, Ben; Boyce, John D
We recently demonstrated that colistin resistance in Acinetobacter baumannii can result from mutational inactivation of genes essential for lipid A biosynthesis (Moffatt JH, et al., Antimicrob. Agents Chemother. 54:4971-4977). Consequently, strains harboring these mutations are unable to produce the major Gram-negative bacterial surface component, lipopolysaccharide (LPS). To understand how A. baumannii compensates for the lack of LPS, we compared the transcriptional profile of the A. baumannii type strain ATCC 19606 to that of an isogenic, LPS-deficient, lpxA mutant strain. The analysis of the expression profiles indicated that the LPS-deficient strain showed increased expression of many genes involved in cell envelope and membrane biogenesis. In particular, upregulated genes included those involved in the Lol lipoprotein transport system and the Mla-retrograde phospholipid transport system. In addition, genes involved in the synthesis and transport of poly-β-1,6-N-acetylglucosamine (PNAG) also were upregulated, and a corresponding increase in PNAG production was observed. The LPS-deficient strain also exhibited the reduced expression of genes predicted to encode the fimbrial subunit FimA and a type VI secretion system (T6SS). The reduced expression of genes involved in T6SS correlated with the detection of the T6SS-effector protein AssC in culture supernatants of the A. baumannii wild-type strain but not in the LPS-deficient strain. Taken together, these data show that, in response to total LPS loss, A. baumannii alters the expression of critical transport and biosynthesis systems associated with modulating the composition and structure of the bacterial surface.
Jan 29, 2018 ... PK principles and rapid achievement of therapeutic concentrations would result in improved clinical cure.[17,20-21]. Combination therapy was prescribed to all but three patients in our study. This practice, including duplicate and sometimes triplicate therapy, is recommended by local guidelines for the ...
English language, peer- reviewed journal ... target steady-state plasma concentrations. A loading .... target AUC/MIC of 60 in patients with normal renal function, nor ..... Landman D, Georgescu C, Martin DA, Quale J. Polymyxins revisited.
Bethesda, Maryland, USAc; University of the Incarnate Word, Feik School of Pharmacy, San Antonio, Texas, USAd; Uniformed Services University of the Health ...survey of renal replacement therapy prescribing prac- tice for acute kidney injury in Malaysian intensive care units. Nephrology (Carlton) 19:507–512
Selected reaction monitoring (SRM) studies were performed on a Thermo TSQ Quantum Ultra Triple Stage quadrupole mass spectrometer. The scans of the...well as a PmrC-dependent pEtN addition to the lipid A of E. coli O157:H7 (39). Surprisingly, the canine pathogen Capnocytophaga canimorsus and plant...variety of novel lipid A structures obtained from Francisella tula- rensis live vaccine strain. Innate Immun. 18:268 –278. 44. Balaji V, Jeremiah SS
Hengzhuang, Wang; Wu, Hong; Ciofu, Oana
) and pharmacodynamics (PDs) of antimicrobials can reliably be used to predict whether antimicrobial regimens will achieve the maximum bactericidal effect against infections. Unfortunately, however, most PK/PD studies of antimicrobials have been done on planktonic cells and very few PK/PD studies have been done...
Bloodstream Infections (BSI) Due to CRE; Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE; Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE; Complicated Urinary Tract Infection (cUTI) Due to CRE; Acute Pyelonephritis (AP) Due to CRE
Full Text Available Historically, the colistin has been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism that colistin induces rapid Paenibacillus polymyxa death through reactive oxygen species production. This significantly augments our understanding of the mechanism of colistin action, which is critical knowledge toward the yield development of colistin in the future.
Nguyen, Nhung T.; Nguyen, Hoa M.; Nguyen, Cuong V.; Nguyen, Trung V.; Nguyen, Men T.; Thai, Hieu Q.; Ho, Mai H.; Thwaites, Guy; Ngo, Hoa T.; Baker, Stephen; Carrique-Mas, Juan
Antimicrobial resistance (AMR) is a global health problem, and emerging semi-intensive farming systems in Southeast Asia are major contributors to the AMR burden. We accessed 12 pig and chicken farms at key stages of production in Tien Giang Province, Vietnam, to measure antimicrobial usage and to
Miller, Amanda K; Brannon, Mark K; Stevens, Laurel
Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 - 64 mg/L) in laboratory and clinical strains...
Result: Cerebrospinal fluid was collected on the 14th day post commencement of colistin and sterilization was attained. Conclusion: Colistin is a potentially effective and safe therapy for the treatment of MDRAB intracrainial ventriculitis. Keywords: Acinetobacter baumannii, colistin, ventriculitis, intraventricular, intrathecal ...
Oddo, Alberto; Thomsen, Thomas Thyge; Kjelstrup, Susanne
. In this study, we investigated the in vitro antibacterial activities of 18 BP100 analogs (four known and 14 new) against the MDR A. baumannii strain ATCC BAA-1605, as well as against a number of other clinically relevant human pathogens. Selected peptides were further evaluated against strains of A. baumannii...
Yildirim, F. Vol 31, No 2 (2015) - Articles Comparison of the efficacy of colistin monotherapy and colistin combination therapies in the treatment of nosocomial pneumonia and ventilator-associated pneumonia caused by Acinetobacter baumannii. Abstract PDF. ISSN: 2078-676X. AJOL African Journals Online. HOW TO USE ...
Comparison of the efficacy of colistin monotherapy and colistin combination therapies in the treatment of nosocomial pneumonia and ventilator-associated pneumonia caused by Acinetobacter baumannii · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. I Kara, F ...
Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang; Adav, Sunil S; Salido, May Margarette; Liu, Yang; Givskov, Michael; Sze, Siu Kwan; Tolker-Nielsen, Tim; Yang, Liang
Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections.
Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang; Adav, Sunil S.; Salido, May Margarette; Liu, Yang; Givskov, Michael; Sze, Siu Kwan; Tolker-Nielsen, Tim; Yang, Liang
Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. PMID:26892159
Azzopardi, Ernest A; Ferguson, Elaine L; Thomas, David W
This study describes the use of a novel, two-compartment, static dialysis bag model to study the release, diffusion, and antibacterial activity of a novel, bioresponsive dextrin-colistin polymer conjugate against multidrug resistant (MDR) wild-type Acinetobacter baumannii. In this model, colistin sulfate, at its MIC, produced a rapid and extensive drop in viable bacterial counts (growth for up to 48 h, with 3 log10 CFU/ml lower bacterial counts after 48 h than those of controls. Doubling the concentration of dextrin-colistin conjugate (to 2× MIC) led to an initial bacterial killing of 3 log10 CFU/ml at 8 h, with a similar regrowth profile to 1× MIC treatment thereafter. The addition of colistin sulfate (1× MIC) to dextrin-colistin conjugate (1× MIC) resulted in undetectable bacterial counts after 4 h, followed by suppressed bacterial growth (3.5 log10 CFU/ml lower than that of control at 48 h). Incubation of dextrin-colistin conjugates with infected wound exudate from a series of burn patients (n = 6) revealed an increasing concentration of unmasked colistin in the outer compartment (OC) over time (up to 86.3% of the initial dose at 48 h), confirming that colistin would be liberated from the conjugate by endogenous α-amylase within the wound environment. These studies confirm the utility of this model system to simulate the pharmacokinetics of colistin formation in humans administered dextrin-colistin conjugates and further supports the development of antibiotic polymer conjugates in the treatment of MDR infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Polymyxins, a group of cationic antimicrobial polypeptides, act as a last-resort defense against lethal infections by carbapenem-resistant Gram-negative pathogens. Recent emergence and fast spread of mobilized colistin resistance determinant mcr-1 argue the renewed interest of colistin in clinical therapies, threatening global public health and agriculture production. This mini-review aims to present an updated overview of mcr-1, covering its global dissemination, the diversity of its hosts/plasmid reservoirs, the complexity in the genetic environment adjacent to mcr-1, the appearance of new mcr-like genes, and the molecular mechanisms for mobilized colistin resistance determinant 1/2 (MCR-1/2).
Jana, Bimal; Cain, Amy K.; Doerrler, William T.
insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential...... for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the “secondary resistome”. As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin...
Chua, Song Lin; Yam, Joey Kuok Hoong; Hao, Piliang
Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino...... acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm...
Baggesen, Dorte Lau; Aarestrup, Frank Møller
A total of 670 isolates of Salmonella enterica were isolated from Danish pig herds, phage typed and tested for susceptibility to amoxycillin + clavulanate, ampicillin, colistin, enrofloxacin, gentamicin, neomycin, spectinomycin, streptomycin, tetracyclines, and trimethoprim + sulphadiazine. S...
Emborg, Hanne-Dorthe; Baggesen, Dorte Lau; Aarestrup, Frank Møller
to the following antimicrobials were determined: ampicillin, chloramphenicol, gentamicin, nalidixic acid, colistin, streptomycin, sulphonamide, tetracycline and trimethoprim. Results: No significant development of resistance occurred within the most important serovars, except Salmonella Typhimurium. A major...
2Department of Neurosurgery, Stroke center, Shanghai Changhai hospital, Shanghai 200433, China ... ventriculitis. Materials and methods: Patient was diagnosed with. MDRAB ... post commencement of colistin and sterilization was attained.
Conclusions: The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii.
Maria Teresa Rosanova
Conclusions: In this series of burn children age ≤ 4 years, Garces index score 4, colistin use in documented multiresistant infections, mechanical ventilation and graft requirement were identified as independent variables related with mortality.
Kassamali, Zahra; Jain, Rupali; Danziger, Larry H
To review recent clinical pharmacokinetic and pharmacodynamic data to optimize dosing regimens for polymyxin B and colistin for treatment of infections due to A. baumannii. A literature search was performed using the search terms Acinetobacter, polymyxin, colistin, polymyxin B on MEDLINE. Additional references were identified from the resulting citations. Increasing the dose of polymyxin B or colistin and using either in combination with other antibiotic agents demonstrates improved antimicrobial activity against Acinetobacter spp. Polymyxin B, unlike colistin, is available as an active drug and appears to be relatively unaffected by renal function. This is advantageous both for patients with renal impairment and for those with intact renal function. Achieving therapeutic serum concentrations of colistin may be difficult for those with intact renal function due to rapid clearance of the prodrug, colistimethate sodium (CMS). Clinical data are still lacking for polymyxin B, and it remains to be seen whether advantages demonstrated in PK/PD analyses will persist in the larger scale of patient care and safety. The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Shah, Pooja G; Shah, Sweta R
Infections caused by carbapenem-resistant bacteria constitute a major challenge for current medical practice. To describe treatment and outcome of carbapenem-resistant Gram-negative bacilli (GNB) blood-stream infection (BSI) caused by these organisms at a tertiary care hospital in Mumbai. Carbapenem-resistant isolates from blood cultures were collected from January 2013 to April 2013. Identification and antimicrobial susceptibility testing were performed using Vitek 2 analyzer (Biomerieux Ltd.). Carbapenemase production was detected by modified Hodge's test (MHT). Patient's medical history, treatment and co-morbid conditions were noted. Outcomes of BSIs were evaluated. Forty-two isolates of carbapenem-resistant GNB isolated from BSIs were Enterobacteriaceae spp. (19), Acinetobacter baumannii (15), and Pseudomonas aeruginosa (8). Colistin had maximum in vitro activity with 97% against Enterobacteriaceae, 100% against Acinetobacter, and 100% activity against Pseudomonas aeruginosa isolates. Positivity of MHT was 92.9%. Outcome of colistin mono and combination therapy was comparable with 83% and 79%, respectively. Outcome of colistin and carbapenem combination therapy was found to be 100 percent. High incidences of bacteremia by carbapenem-resistant GNB including Enterobacteriaceae is a worrisome trend. Treatment options are compromised and only available option is colistin which has its own limitation. Colistin monotherapy may be non-inferior compared to combination therapy for treating BSIs caused by isolates with minimum inhibitory concentration (MIC) for colistin as ≤0.5 mg/l. Combined use of the colistin and carbapenem may provide good therapeutic options for BSI caused by carbapenem-resistant GNB and warrants further investigations.
Rafailidis, Petros I; Falagas, Matthew E
To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months. Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations. Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.
Kluytmans-van den Bergh, Marjolein F; Huizinga, Pepijn; Bonten, Marc J; Bos, Martine; De Bruyne, Katrien; Friedrich, Alexander W; Rossen, John W; Savelkoul, Paul H; Kluytmans, Jan A
Recently, the plasmid-mediated colistin resistance gene mcr-1 was found in Enterobacteriaceae from humans, pigs and retail meat in China. Several reports have documented global presence of the gene in Enterobacteriaceae from humans, food animals and food since. We screened several well-characterised strain collections of Enterobacteriaceae, obtained from retail chicken meat and hospitalised patients in the Netherlands between 2009 and 2015, for presence of colistin resistance and the mcr-1 gene. A total of 2,471 Enterobacteriaceae isolates, from surveys in retail chicken meat (196 isolates), prevalence surveys in hospitalised patients (1,247 isolates), clinical cultures (813 isolates) and outbreaks in healthcare settings (215 isolates), were analysed. The mcr-1 gene was identified in three (1.5%) of 196 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates from retail chicken meat samples in 2009 and 2014. Two isolates were obtained from the same batch of meat samples, most likely representing contamination from a common source. No mcr-1-positive isolates were identified among 2,275 human isolates tested. All mcr-1-positive isolates were colistin-resistant (minimum inhibitory concentration (MIC) > 2 mg/L). Our findings indicate that mcr-1-based colistin-resistance currently poses no threat to healthcare in the Netherlands. They indicate however that continued monitoring of colistin resistance and its underlying mechanisms in humans, livestock and food is needed.
Full Text Available Abstract Background The extent of the occurrence of the plasmid-encoded colistin resistance genes mcr-1 and mcr-2 among humans is currently sparsely studied in Western Europe. Objectives To determine the occurrence of MCR-producing Enterobacteriaceae in fecal samples of healthy humans with high occupational exposure to food and primary care patients in Switzerland. Methods Stool samples from 1091 healthy individuals and fecal swabs from 53 primary care patients were screened for polymyxin-resistant Enterobacteriaceae using LB agar containing 4 mg/L colistin. Minimal inhibitory concentrations (MICs of colistin were determined for non-intrinsic colistin-resistant isolates. Isolates were screened by PCR for the presence of mcr-1 and mcr-2 genes. Results The fecal carriage rate of colistin resistant (MIC value >2 mg/l Enterobacteriaceae was 1.5% for healthy people and 3.8% for primary care patients. Isolates included Hafnia alvei (n = 9, Escherichia coli (n = 3, Enterobacter cloacae (n = 4, Klebsiella pneumoniae (n = 1 and Raoultella ornithinolytica (n = 1. None of the isolates harbored the mcr-1 or mcr-2 genes. Conclusions There is no evidence for the presence of MCR-producers in the fecal flora of healthy people or primary care patients. Therefore, the risk of transfer of mcr genes from animals, food or the environment to humans is likely to be low in Switzerland.
pleiotropy as they conferred a decreased growth rate in the absence of colistin and also rendered the colistin resistant strains susceptible towards all tested classes of β-lactams. The results suggest that colistin/β-lactam combination therapy could be used to reduce the risk of resistance evolution during......The evolution of antimicrobial resistance in bacterial pathogens is a growing global health problem that is gradually making the successful treatment of infectious diseases more difficult. Antimicrobial peptides have been proposed as promising candidates for future drug development as they retain...... activity against bacteria resistant to conventional antibiotics and because resistance evolution is expected to be unlikely since the peptides have complex modes of action due to their interaction with the bacterial membrane. The work presented in this thesis has involved studies to increase our...
Kengkla, Kirati; Kongpakwattana, Khachen; Saokaew, Surasak; Apisarnthanarak, Anucha; Chaiyakunapruk, Nathorn
To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Sathe, Prachee; Maddani, Sagar; Kulkarni, Shilpa; Munshi, Nita
Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii). This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed. Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin. Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases. Copyright © 2017 Elsevier Inc. All rights reserved.
Survey of Antibiotic Resistance and Frequency of blaOXA-23 and blaOXA-24 Oxacillinase in Acinetobacter baumannii Isolated from Tracheal Tube Specimens of Patients Hospitalized in Intensive Care Units in Isfahan city
chi-square tests. Results: All isolates were found resistant to ceftazidime, ceftriaxone, meropenem and imipenem and the lowest resistance were seen against colistin (0% and tigecycline (10%, respectively. All isolates were resistant to imipenem using Etest method with MIC ≥ 32 μg / ml. blaOXA-23 and blaOXA-24 genes were detected in 87.5% and 25% of isolates, respectively. Conclusion: Due to the results, treatment of A. baumannii isolates by carbapenems is ineffective and tigecycline or colistin could be used for treatment. Other studies for detection of other mechanisms for carbapenem resistance are recommended.
Delgado-Blas, Jose F; Ovejero, Cristina M; Abadia-Patiño, Lorena; Gonzalez-Zorn, Bruno
We studied the presence of the mobile colistin resistance gene mcr-1 in human, animal, and environmental Enterobacteriaceae samples from Cumana, Venezuela, that were collected in 2015. The mcr-1 gene was detected in 2/93 Escherichia coli isolates from swine (novel ST452) and human (ST19) samples that were resistant to colistin. Whole-genome sequencing and transformation experiments identified mcr-1 on an IncI2 plasmid. One of the isolates also bore the widely spread carbapenemase NDM-1. A One Health approach is necessary to further elucidate the flux of these high-risk genes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Full Text Available An agar disc diffusion method was used to examine the sensitivity of 27 Haemophilus paragallinarum (Hpg isolates consisted of 23 local isolates, 4 standard isolates (serotype A and Escherichia coli ATCC 24922 as a control to eight antimicrobial drugs (ampicillin, erythromycin, oxytetracycline, doxycycline, neomycin, streptomycin, colistine and sulphanlethoxazole-trimethoprim . Twenty one out of 23 local isolates of Hpg were sensitive to doxycycline, 19 isolates to ampsllin, 18 isolates to oxytetracycline, 17 isolates to sulphametoxazole-trimethoprim, 16 isolates to erythromycin, and 13 isolates to neomycin, while 13 isolates were resistance to colistine and 11 isolates were also resistance to streptomycin .
Bonten, Marc J.M.
In November 2015, plasmid-mediated colistin resistance in Gram-negative bacteria was reported for the first time, and it was evident that this newly-identified resistance gene (mcr-1) was already prevalent in the animal and human reservoir in China. As well as massive media attention, there was also
account for almost threequarters of all Acinetobacter baumannii bloodstream infections, supporting the decision to include colistin or tobramycin as empirical treatment options for ICU patients with suspected Gramnegative sepsis. The dissemination and utilisation of surveillance data is crucial if they are to impact on patient ...
Conclusion: The finding of the study therefore indicates that carbapenem resistance is mediated by carbapenemase production and or overproduction of ESBL coupled with reduced porins. Co-production of carbapenemase, MBLs and ESBLs by some of the isolates is worrisome. Susceptibility to colistin and tigecycline was ...
Conclusion: To the best of our knowledge, this study is the first to describe the microbiological characteristics of CRAB ST787, which carried high genetic resistance to carbapenem, but remained susceptible to colistin. CRAB ST787 was the predominant clone in our hospital in the study period.
Pedersen, Karl; Hammer, Anne Sofie; Sørensen, Charlotte Mark
, whereas resistance to other antimicrobials was rare. All P aeruginosa were sensitive to gentamicin and colistin and sensitive or intermediate to enrofloxacin. whereas most isolates were resistant to all other antimicrobials. All P. multocida and haemolytic streptococci were sensitive to penicillin...
JOHN OSEI SEKYERE
Full Text Available A review of the literature was undertaken to delineate the current level and mechanisms of resistance to carbapenems, colistin and tigecycline in South Africa. Thirty-two English publications and 32 National Institute of Communicable Diseases (NICD communiqués identified between early January 2000 and 20th May, 2016 showed substantial reports of NDM (n=860, OXA-48 (n=584, VIM (n=131 and IMP (n=45 carbapenemases within this period, mainly in Klebsiella pneumoniae (n=1138, Acinetobacter baumannii (n=332, Enterobacter cloacae (n=201 and Serratia marcescens (n=108. Colistin and tigecycline resistance was prevalent among K. pneumoniae, A. baumannii, S. marcescens and E. cloacae. The first mcr-1 colistin resistance gene to be detected in South Africa was reported in E. coli from livestock as well as from hospitalized and out patients. There are increasing reports of NDM and OXA-48 carbapenemases among Enterobacteriaceae and A. baumannii in South Africa. Mcr-1 is now present in South African patients and livestock. Resistance to carbapenems, colistin and tigecycline restricts infection management options for clinicians.
Ellem, Justin A; Ginn, Andrew N; Chen, Sharon C-A; Ferguson, John; Partridge, Sally R; Iredell, Jonathan R
We identified discrete importation events of the mcr-1 gene on incompatibility group IncI2 plasmids in Escherichia coli isolated from patients in New South Wales, Australia, in 2011 and 2013. mcr-1 is present in a small minority of colistin-resistant Enterobacteriaceae and appears not to be established locally.
Jana, Bimal; Cain, Amy K; Doerrler, William T; Boinett, Christine J; Fookes, Maria C; Parkhill, Julian; Guardabassi, Luca
Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the "secondary resistome". As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial "helper" drugs that restore the efficacy of existing antimicrobials.
Conclusion: This study clearly showed the high prevalence of resistance to broad-spectrum beta-lactam antibiotics in the isolated E. cloacae among which 5% were multi drug resistant. All the isolated E. cloacae were susceptible to Colistin. These results can be alarming for physicians treating resistant E. cloacae infections, especially extended-spectrum beta-lactamase producing species.
Adelowo, Olawale O.; Fagade, Obasola E.; Agersø, Yvonne
%, ampicillin 36%, spectinomycin 28%, nalidixic acid 25%, chloramphenicol 22%, neomycin 14%, gentamicin 8%, amoxicillin-clavulanate, ceftiofur, cefotaxime, colistin, florfenicol and apramycin 0%. Resistance genes found among the isolates include bla-TEM (85%), sul2 (67%), sul3 (17%), aadA (65%), strA (70%), str...
Introduction: Escherichia coli O157:H7 (O157) can cause diarrhea and serious secondary sequelae including kidney failure and death in humans. With antibiotics like fosfomycin, colistin and azithromycin, that do not stimulate toxin expression by O157, being considered for treatment of early gastroint...
Xu, Yongchang; Wei, Wenhui; Lei, Sheng; Lin, Jingxia; Srinivas, Swaminath; Feng, Youjun
Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA , the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli , Salmonella enterica , Klebsiella pneumoniae , etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and p hospho e thanol a mine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens. IMPORTANCE EptA and MCR-1 and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a final resort against carbapenem-resistant pathogens. Structural and functional analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing cavities, which explains intrinsic and
Morici, P; Florio, W; Rizzato, C; Ghelardi, E; Tavanti, A; Rossolini, G M; Lupetti, A
The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.
Full Text Available Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin conferred by Neisseria eptA, the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE. The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, etc., rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and phosphoethanolamine [PEA] transferase are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens.
Folkesson, Anders; Haagensen, Janus Anders Juul; Zampaloni, Claudia
Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We address the question of how biofilm organization affects antibiotic susceptibility. We established Escherichia coli biofilms with differential structural organization due...... to the presence of IncF plasmids expressing altered forms of the transfer pili in two different biofilm model systems. The mature biofilms were subsequently treated with two antibiotics with different molecular targets, the peptide antibiotic colistin and the fluoroquinolone ciprofloxacin. The dynamics...... of microbial killing were monitored by viable count determination, and confocal laser microscopy. Strains forming structurally organized biofilms show an increased bacterial survival when challenged with colistin, compared to strains forming unstructured biofilms. The increased survival is due to genetically...
Full Text Available 187 commercial checken flocks affected with respiratory diseases were examined for Ornithobacterium rhinotracheale isolation. The bacterium was isolated from 105 (56.2% poultry flocks. Drug sensitivity test using standard disk diffusion technique was performed with 19 antibiotics. All the isolates were susceptible to tiamulin and most of them were susceptible to chloramphenicol and linco-spectin. All the isolates were resistant to sulfamethoxazol-trimethoprim, colistin and neomycin and most of them were resistant to gentamycin, lincomycin, erythromycin, tetracycline and enrofloxacin. One isolate from a native turkey was also tested. This isolate was resistant to sulfamethoxazole-trimethoprim, colistin, neomycin and gentamycin, but was sensitive to other tested antimicrobials. Because of acquired antibiotic resistance, the various result of antibiotic therapy, it must be stressed to prevent the infection.
Full Text Available Bacteria of the genus Acinetobacter, especially species Acinetobacter baumanii, is one of the most important causes of infection in immunocompromised patients in hospital. The aim of this study was to determine susceptibility of Acinetobacter species isolated from swabs of inflamed wounds to antibiotics. The study was conducted in several departments of the Clinical Centre 'Kragujevac' through retrospective analysis of 220 Acinetobacter species isolates from surgical wounds in 2011. The isolates of Acinetobaster species were mostly sensitive to ampicillin-sulbactam, colistin and tigecycline in all hospital departments that were surveyed. Only minority of the isolated Acinetobacter species were susceptible to cotrimoxazole, amikacin, imipenem and/or meropenem. Antibiotics with the highest in vitro efficacy against Acinetobacter species were ampicillinsulbactam, colistin and tigecycline. Highly resistant Acinetobacter species were more frequently isolated from patients in Intensive Care Unit.
Full Text Available Polymyxins (polymyxin B and colistin are cyclic lipopeptide antibiotics that serve as a last-line defence against Gram-negative “superbugs”. In the present study, two novel fluorescent polymyxin probes were designed through regio-selective modifications of the polymyxin B core structure at the N-terminus and the hydrophobic motif at positions 6 and 7. The resulting probes, FADDI-285 and FADDI-286 demonstrated comparable antibacterial activity (MICs 2–8 mg/L to polymyxin B and colistin (MICs 0.5–8 mg/L against a panel of gram-negative clinical isolates of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. These probes should prove to be of considerable utility for imaging cellular uptake and mechanistic investigations of these important last-line antibiotics.
Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L
In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Rottbøll, Lisa Amanda Holm; Friis, Christian
), using intrabronchial microdialysis. The series of drugs tested include gentamicin, sulfadiazine, cefquinome, minocycline and colistin. METHODS: Drug concentrations were measured during 2h of steady state plasma drug concentrations at therapeutic levels in anesthetized pigs. Microdialysis probes were...... positioned 2 to 4cm distal to the tracheal bifurcature and in M. gluteobiceps and were calibrated by retrodialysis by drug. RESULTS: Mean AUCPELF/PLASMA(fu) and mean AUCMUSCLE/PLASMA(fu) ratios were respectively for gentamicin (0.8, 0.7), sulfadiazine (1.1, 0.7), cefquinome (1.3, 1.5) minocycline (1.6, 0...... for the passively transported drugs gentamicin, sulfadiazine, cefquinome and colistin, whereas minocycline appears to be actively transported into PELF....
Starke, I D; Donnelly, P; Catovsky, D; Darrell, J; Johnson, S A; Goldman, J M; Galton, D A
43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.
Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark
UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second...... antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA...
type, oligomeric donor monomers with fused thienobenzothiophene structures. These monomers are copolymerized with fluorinated thieno[3,4- b]thiophene...copolymerized with fluorinated thieno[3,4- b]thiophene ester to form a series of polymers which were investigated as donor materials in polymer/fullerene...effective but somewhat toxic drug, significantly lowered the dose of colistin required for killing bacteria and thus increased its safety. These
منصور بنانی; سیدعلی پوربخش; ا.ح. دیهیمی
187 commercial checken flocks affected with respiratory diseases were examined for Ornithobacterium rhinotracheale isolation. The bacterium was isolated from 105 (56.2%) poultry flocks. Drug sensitivity test using standard disk diffusion technique was performed with 19 antibiotics. All the isolates were susceptible to tiamulin and most of them were susceptible to chloramphenicol and linco-spectin. All the isolates were resistant to sulfamethoxazol-trimethoprim, colistin and neomycin and most ...
Dalsgaard, A.; Dalsgaard, Inger; Høi, L.
Methods for the identification and isolation of environmental isolates of Vibrio vulnificus were evaluated. Alkaline peptone water supplemented with polymyxin B and colistin-polymyxin B- cellobiose agar were employed for the isolation of suspected V. vulnificus from water, sediment and shellfish ...... hybridizing with the probe. The results indicated that, compared with colony hybridization, the API 20E assay was not adequate for the identification of environmental isolates of V. vulnificus....
Moussounda, Mesmin; Diene, Seydina M; Dos Santos, Sandra; Goudeau, Alain; François, Patrice; van der Mee-Marquet, Nathalie
Reports of carbapenemase-producing Enterobacteriaceae in Africa remain rare and assess mostly bla OXA-48 -producing isolates from Mediterranean countries and South Africa. We identified bla NDM-7 -producing Enterobacteriaceae in Gabon in 2016. The isolates contained bla NDM-7 IncX3 plasmids that were unusual and similar to the one described in a colistin-resistant Klebsiella pneumoniae SZ04 isolate from China.
de Maio Carrilho, Claudia M D; de Oliveira, Larissa Marques; Gaudereto, Juliana; Perozin, Jamile S; Urbano, Mariana Ragassi; Camargo, Carlos H; Grion, Cintia M C; Levin, Anna Sara S; Costa, Silvia F
To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.
Full Text Available The increasing prevalence of multidrug-resistant nosocomial pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae poses a great challenge to the treating physicians. The paucity of newer effective antimicrobials has led to renewed interest in the polymyxin group of drugs, as a last resort for treatment of gram-negative bacterial infections. There is a dearth of information on the pharmacological properties of colistin, leading to difficulties in selecting the right dose, dosing interval, and route of administration for treatment, especially in critically-ill patients. The increasing use of colistin over the last few years necessitates the need for accurate and reliable in vitro susceptibility testing methods. Development of heteroresistant strains as a result of colistin monotherapy is also a growing concern. There is a compelling need from the clinicians to provide options for probable and possible colistin combination therapy for multidrug-resistant bacterial infections in the ICU setting. Newer combination drug synergy determination tests are being developed and reported. There are no standardized recommendations from antimicrobial susceptibility testing reference agencies for the testing and interpretation of these drug combinations. Comparison and analysis of these reported methodologies may help to understand and assist the microbiologist to choose the best method that produces accurate results at the earliest. This will help clinicians to select the appropriate combination therapy. In this era of multidrug resistance it is important for the microbiology laboratory to be prepared, by default, to provide timely synergistic susceptibility results in addition to routine susceptibility, if warranted. Not as a favour or at request, but as a responsibility.
Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D.; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel
Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, ...
Full Text Available Salmonella is frequently found in poultry and represent an important source for human gastrointestinal infections worldwide. The aim of this study was to investigate the prevalence, genotypes and antimicrobial resistance of Salmonella serotypes in broilers from Ecuador. Caeca content from 388 at random selected broiler batches were collected in 6 slaughterhouses during 1 year and analyzed by the ISO 6579/Amd1 protocol for the isolation for Salmonella. Isolates were serotyped and genotypic variation was acceded by pulsed field gel electrophoresis. MIC values for sulfamethoxazole, gentamicin, ciprofloxacin, ampicillin, cefotaxime, ceftazidime, tetracycline, streptomycin, trimethropim, chloramphenicol, colistin, florfenicol, kanamycin and nalidixic acid were obtained. Presence of blaCTX-M, blaTEM, blaSHV and blaCMY; and mcr-1 plasmid genes was investigated in resistant strains to cefotaxime and colistin respectively. Prevalence at batch level was 16.0%. The most common serotype was S. Infantis (83.9% followed by S. Enteritidis (14.5% and S. Corvallis (1.6%. The pulsed field gel electrophoresis analysis showed that S. Corvallis, S. Enteritidis and S. Infantis isolates belonged to 1, 2 and 12 genotypes respectively. S. Infantis isolates showed high resistance rates to 12 antibiotics ranging from 57.7% (kanamycin up to 98.1% (nalidixic acid and sulfamethoxazole. All S. Enteritidis isolates showed resistance to colistin. High multiresistant patterns were found for all the serotypes. The blaCTX-M gene was present in 33 S. Infantis isolates while mcr-1 was negative in 10 colistin resistant isolates. This study provides the first set of scientific data on prevalence and multidrug-resistant Salmonella coming from commercial poultry in Ecuador.
Hunt, D E; Jones, J V; Dowell, V R
Bacteroides gingivalis has been implicated in various forms of periodontal disease and may be responsible for other diseases in humans. The role of B. gingivalis in disease has been difficult to assess, because it is inhibited by most selective media commonly used by clinical laboratories to aid in isolating gram-negative, nonsporeforming anaerobes. We have developed a new medium, Bacteroides gingivalis agar, which contains bacitracin, colistin, and nalidixic acid as selective agents. This me...
Green, M; Wadowsky, R M; Barbadora, K
A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium....
Rodríguez Guardado, A; Blanco, A; Asensi, V; Pérez, F; Rial, J C; Pintado, V; Bustillo, E; Lantero, M; Tenza, E; Alvarez, M; Maradona, J A; Cartón, J A
The treatment of multidrug-resistant Acinetobacter baumannii meningitis is a serious therapeutic problem due to the limited penetration of antibiotics into the CSF. We describe the clinical features and the outcome of a group of patients with nosocomial neurosurgical meningitis treated with different therapeutic options. All patients with nosocomial post-surgical meningitis due to A. baumannii diagnosed between 1990 and 2004 were retrospectively reviewed. During the period of study, 51 cases of this nosocomial infection were identified. Twenty-seven patients were treated with intravenous (iv) monotherapy: carbapenems (21 cases), ampicillin/sulbactam (4 cases) and other antibiotics (2 cases). Four patients were treated with iv combination therapy. Nineteen patients were treated with iv and intrathecal regimens: colistin by both routes (8 cases), carbapenems plus iv and intrathecal (4 cases) or only intrathecal (5 cases) aminoglycosides, and others (2 cases). Seventeen patients died due to the infection. One patient died without treatment. The mean (SD) duration of therapy was 17.4 (8.3) days (range 3-44). Although no patients treated with colistin died, we did not observe statistically significant differences in the mortality among the groups with different treatments. Nosocomial Acinetobacter meningitis has a high mortality. Combined therapy with iv and intrathecal colistin is a useful and safe option in the treatment of nosocomial Acinetobacter meningitis.
محمدحسن بزرگمهری فرد
Full Text Available The effect of colistin sulfate on reducing Salmonella enteritidis (S.enteritidis infection in broilers and contamination from broiler carcasses was evaluated. 40000 birds in two separate houses were considered. Colistin sulfate was added in to the feed of the test group as 100g containing 1,200,000IU/ton of feed for the whole period (56 days. To isolate S.enteritidis, samples were taken from different parts of the intestine and cultured in Selenite broth and then on SS agar plates. The suspected colonies were isolated and identified by biochemical and serological tests. It is conducted that the addition of the above mentioned amount of this antibiotic in to the broiler feed could decrease the rate of the infection of flocks and contamination of carcasses with S.enteritidis. The results also indicate that due to addition of colistin sulfate, the live weight gain increases by 14% and the feed conversion rate improves by 8% in this study.
Hu, Yi-Fan; Liu, Chang-Pan; Wang, Nai-Yu; Shih, Shou-Chuan
Multidrug-resistant Pseudomonas aeruginosa has emerged as one of the most important healthcare-associated pathogens. Colistin is regarded as the last-resort antibiotic for multidrug-resistant Gram-negative bacteria, but is associated with high rates of acute kidney injury. The aim of this in vitro study is to search for an alternative treatment to colistin for multidrug-resistant P. aeruginosa infections. Multidrug and carbapenem-resistant P. aeruginosa isolates were collected between January 2009 and December 2012 at MacKay Memorial Hospital. Minimal inhibitory concentrations (MICs) were determined for various antibiotic combinations. Carbapenemase-producing genes including bla VIM, other β-lactamase genes and porin mutations were screened by PCR and sequencing. The efficacy of carbapenems (imipenem, meropenem, doripenem) with or without rifampicin was correlated with the type of porin mutation (frameshift mutation, premature stop codon mutation) in multidrug-resistant P. aeruginosa isolates without carbapenemase-producing genes. Of the 71 multidrug-resistant clinical P. aeruginosa isolates, only six harboured the bla VIM gene. Imipenem, meropenem and doripenem were significantly more effective (reduced fold-change of MICs) when combined with rifampicin in bla VIM-negative isolates, especially in isolates with porin frameshift mutation. Imipenem + rifampicin combination has a low MIC against multidrug-resistant P. aeruginosa, especially in isolates with porin frameshift mutation. The imipenem + rifampicin combination may provide an alternative treatment to colistin for multidrug -resistant P. aeruginosa infections, especially for patients with renal insufficiency.
P V Saiprasad
Full Text Available Gram-negative resistance is a serious global crisis putting the world on the cusp of 'pre-antibiotic era'. This serious crisis has been catalysed by the rapid increase in carbapenem-resistant Enterobacteriaceae (CRE. Spurge in colistin usage to combat CRE infections leads to the reports of (colistin and carbapenem resistant enterobacteriaceae CCRE (resistance to colistin in isolates of CRE infections further jeopardising our last defence. The antibacterial apocalypse imposed by global resistance crisis requires urgent alternative therapeutic options. Interest in the use of fosfomycin renewed recently for serious systemic infections caused by multidrug-resistant Enterobacteriaceae. This review aimed at analysing the recent evidence on intravenous fosfomycin to explore its hidden potential, especially when fosfomycin disodium is going to be available in India. Although a number of promising evidence are coming up for fosfomycin, there are still areas where more work is required to establish intravenous fosfomycin as the last resort antibacterial for severe Gram-negative infections.
Ostorhazi, Eszter; Rozgonyi, Ferenc; Sztodola, Andras; Harmos, Ferenc; Kovalszky, Ilona; Szabo, Dora; Knappe, Daniel; Hoffmann, Ralf; Cassone, Marco; Wade, John D; Bonomo, Robert A; Otvos, Laszlo
The designer antibacterial peptide A3-APO is efficacious in mouse models of Escherichia coli and Acinetobacter baumannii systemic infections. Here we compare the efficacy of the peptide with that of imipenem and colistin in A. baumannii wound infections after burn injury. CD-1 mice were inflicted with burn wounds and different inocula of A. baumannii, isolated from an injured soldier, were placed into the wound sites. The antibiotics were given intramuscularly (im) one to five times. Available free peptide in the blood and the systemic toxicity of colistin and A3-APO were studied in healthy mice. While toxicity of colistin was observed at 25 mg/kg bolus drug administration, the lowest toxic dose of A3-APO was 75 mg/kg. In the A. baumannii blast injury models, 5 mg/kg A3-APO improved survival and reduced bacterial counts in the blood as well as in the wounds and improved wound appearance significantly better than any other antibiotic treatment. The free peptide concentration in the blood did not reach 1 µg/mL. Peptide A3-APO, with an intramuscular therapeutic index of 15, is more efficacious and less toxic than any existing burn injury infection therapy modality against multidrug-resistant Gram-negative pathogens. A3-APO administered by the im route probably binds to a biopolymer that promotes the peptide's biodistribution.
Bakthavatchalam, Yamuna Devi; Pragasam, Agila Kumari; Biswas, Indranil; Veeraraghavan, Balaji
Emerging multidrug-resistant (MDR) nosocomial pathogens are a great threat. Polymyxins, an old class of cationic polypeptide antibiotic, are considered as last-resort drugs in treating infections caused by MDR Gram-negative bacteria. Increased use of polymyxins in treating critically ill patients necessitates routine polymyxin susceptibility testing. However, susceptibility testing both of colistin and polymyxin B (PMB) is challenging. In this review, currently available susceptibility testing methods are briefly discussed. The multicomponent composition of colistin and PMB significantly influences susceptibility testing. In addition, poor diffusion in the agar medium, adsorption to microtitre plates and the synergistic effect of the surfactant polysorbate 80 with polymyxins have a great impact on the performance of susceptibility testing methods This review also describes recently identified chromosomal resistance mechanisms, including modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose (L-Ara4-N) and phosphoethanolamine (pEtN) resulting in alteration of the negative charge, as well as the plasmid-mediated colistin resistance determinants mcr-1, mcr-1.2, mcr-2 and mcr-3. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.
Full Text Available A third plasmid-mediated colistin resistance gene, mcr-3, is increasingly being reported in Enterobacteriaceae and Aeromonas spp. from animals and humans. To investigate the molecular epidemiology of mcr in the gut flora of Chinese outpatients, 152 stool specimens were randomly collected from outpatients in our hospital from May to June, 2017. Stool specimens enriched in alkaline peptone water or Luria-Bertani (LB broth were screened for mcr-1, mcr-2, and mcr-3 using polymerase chain reaction (PCR-based assays. Overall, 19.1% (29/152 and 5.3% (8/152 of the stool samples enriched in alkaline peptone water were PCR-positive for mcr-1 and mcr-3, respectively, while 2.7% (4/152 of samples were positive for both mcr-1 and mcr-3. Strains isolated from the samples that were both mcr-1- and mcr-3-positive were subjected to antimicrobial susceptibility testing by broth microdilution. They were also screened for the presence of other resistance genes by PCR, while multilocus sequence typing and whole-genome sequencing were used to investigate the molecular epidemiology and genetic environment, respectively, of the resistance genes. mcr-3-positive Aeromonas veronii strain 126-14, containing a mcr-3.8-mcr-3-like2 segment, and mcr-1-positive Escherichia coli strain 126-1, belonging to sequence type 1485, were isolated from the sample from a diarrheic butcher with no history of colistin treatment. A. veronii 126-14 had a colistin minimum inhibitory concentration (MIC of 2 µg/mL and was susceptible to antibiotics in common use, while E. coli 126-1 produced TEM-1, CTX-M-55, and CTX-M-14 β-lactamases and was resistant to colistin, ceftazidime, and cefotaxime. Overall, there was a higher detection rate of mcr-3-carrying strains with low colistin MICs from the samples enriched in alkaline peptone water than from samples grown in LB broth.
Maraki, Sofia; Mantadakis, Elpis; Mavromanolaki, Viktoria Eirini; Kofteridis, Diamantis P; Samonis, George
Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010-2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin
Ovejero, C M; Delgado-Blas, J F; Calero-Caceres, W; Muniesa, M; Gonzalez-Zorn, B
The mobile colistin resistance gene mcr-1 has been identified worldwide in human and animal sources, while its occurrence in the environment is still largely unknown. The aim of this study was to investigate the presence of mcr-1 -harbouring Enterobacteriaceae in water samples obtained from rivers and waste water treatment plants in the area of Barcelona, Spain. The presence of mcr-1 was detected by PCR. Bacterial identification was performed via MALDI-TOF MS. Resistance to colistin was determined by a broth dilution method. The epidemiological relationship between the positive isolates was assessed with PFGE and ST was determined by MLST. Plasmid characterization was performed by transformation experiments, antimicrobial susceptibility testing and incompatibility group PCR. Thirty MDR isolates bearing mcr-1 , 29 Escherichia coli (ST632 and ST479) and 1 Klebsiella pneumoniae (ST526), were identified in sewage from two different waste water treatment plants, whereas the gene was not found in river water. All isolates, including the K. pneumoniae , harboured bla CTX-M-55 and bla TEM-1 . mcr-1 was in all cases associated with an IncI2 plasmid, which only conferred resistance to colistin. mcr-1 was harboured by two predominant E. coli clones that were found in both waste water treatment plants. This study showed a high occurrence of mcr-1 in the sewage of Barcelona, mainly due to the dissemination of two E. coli pulsotypes that are circulating in the population. The presence of mcr-1 in the environment is a cause for concern, and suggests high prevalence of mcr-1 in the community. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: email@example.com.
Choi, Hyeon Jin; Kil, Min Cheol; Choi, Ji-Young; Kim, Sun Ju; Park, Ki-Sup; Kim, Yae-Jean; Ko, Kwan Soo
In this study, 38 Acinetobacter baumannii isolates successively isolated from blood, skin swabs and tracheal aspirates from a single patient who died from haemophagocytic lymphohistiocytosis were investigated. The isolates were collected between March 2012 and August 2012. A. baumannii genotypes were determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In vitro antimicrobial susceptibility testing was performed and colistin heteroresistance and persistence were evaluated. The structure of AbaR resistance islands was explored, and serum sensitivity was determined. Based on MLST analysis, all 38 A. baumannii isolates showed the same sequence type (ST138). However, PFGE analysis showed that isolates from blood samples belonged to different genotypes depending on the isolation time: whilst blood isolates obtained at the early stages showed restriction patterns similar to those of isolates from other sources, isolates obtained at later stages exhibited a distinct pattern. All isolates were resistant to imipenem, cefepime, ciprofloxacin and piperacillin/tazobactam. Five isolates from tracheal aspirates and one from a skin swab were resistant to polymyxins, and two isolates from skin swabs and one from another source were non-susceptible to tigecycline. All colistin-susceptible isolates showed heteroresistance to colistin, and four were persisters. Isolates from blood showed higher survival rates against human serum than those from other sources. This study shows that the patient was infected with more than one A. baumannii strain. Heteroresistance, persistence or evasion of the innate immune response may explain the failure of antimicrobial treatments in this patient. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Full Text Available Emergence of multidrug-resistant Acinetobacter baumannii (MDRAB has become a critical clinical problem worldwide and limited therapeutic options for infectious diseases caused by MDRAB. Therefore, there is an urgent need for the development of new antimicrobial agents or alternative therapy to combat MDRAB infection. The aim of this study was to investigate effects of Mastoparan-AF (MP-AF, an amphipathic peptide isolated from the hornet venom of Vespa affinis with broad-spectrum antimicrobial activity, on MDRAB. As compared with clinical used antibiotics, MP-AF exhibited potent antimicrobial activity at 2–16 μg/ml against the reference strain A. baumannii ATCC 15151 and seven MDRAB clinical isolates, especially the colistin-resistant MDRAB, E0158. The synergistic antimicrobial combination study revealed that MP-AF acted synergistically with specific antibiotics, e.g., ciprofloxacin, trimethoprim/sulfamethoxazole (SXT or colistin against some isolates of the MDRAB. It was noteworthy when MP-AF combined with SXT exhibited synergistic activity against all SXT-resistant MDRAB isolates. The synergistic combination of MP-AF and antibiotics could reduce the dosage recommended of each antimicrobial agent and improve the safety of medications with ignorable adverse effects, such as colistin with nephrotoxicity in therapeutic dose. Furthermore, MP-AF combined with antibiotics with different antimicrobial mechanisms could reduce selective pressure of antibiotics on bacteria and prevent the emergence of antimicrobial-resistant strains. Importantly, we are the first finding that MP-AF could make MDRAB from the original non-susceptibility to SXT become sensitivity. In conclusion, MP-AF alone or in combination with other antibiotics, especially SXT, is a potential candidate against MDRAB infection in clinical medicine.
Irrgang, Alexandra; Roschanski, Nicole; Tenhagen, Bernd-Alois; Grobbel, Mirjam; Skladnikiewicz-Ziemer, Tanja; Thomas, Katharina; Roesler, Uwe; Käsbohrer, Annemarie
Since the first description of a plasmid-mediated colistin resistance gene (mcr-1) in November 2015 multiple reports of mcr-1 positive isolates indicate a worldwide spread of this newly discovered resistance gene in Enterobacteriaceae. Although the occurrence of mcr-1 positive isolates of livestock, food, environment and human origin is well documented only few systematic studies on the prevalence of mcr-1 are available yet. Here, comprehensive data on the prevalence of mcr-1 in German livestock and food isolates are presented. Over 10.600 E. coli isolates from the national monitoring on zoonotic agents from the years 2010-2015 were screened for phenotypic colistin resistance (MIC value >2 mg/l). Of those, 505 resistant isolates were screened with a newly developed TaqMan-based real-time PCR for the presence of the mcr-1 gene. In total 402 isolates (79.8% of colistin resistant isolates) harboured the mcr-1 gene. The prevalence was depending on the food production chain. The highest prevalence was detected in the turkey food chain (10.7%), followed by broilers (5.6%). A low prevalence was determined in pigs, veal calves and laying hens. The mcr-1 was not detected in beef cattle, beef and dairy products in all years investigated. In conclusion, TaqMan based real-time PCR provides a fast and accurate tool for detection of mcr-1 gene. The overall detection rate of 3.8% for mcr-1 among all E. coli isolates tested is due to high prevalence of mcr-1 in poultry production chains. More epidemiological studies of other European countries are urgently needed to assess German prevalence data.
Full Text Available Since the first description of a plasmid-mediated colistin resistance gene (mcr-1 in November 2015 multiple reports of mcr-1 positive isolates indicate a worldwide spread of this newly discovered resistance gene in Enterobacteriaceae. Although the occurrence of mcr-1 positive isolates of livestock, food, environment and human origin is well documented only few systematic studies on the prevalence of mcr-1 are available yet. Here, comprehensive data on the prevalence of mcr-1 in German livestock and food isolates are presented. Over 10.600 E. coli isolates from the national monitoring on zoonotic agents from the years 2010-2015 were screened for phenotypic colistin resistance (MIC value >2 mg/l. Of those, 505 resistant isolates were screened with a newly developed TaqMan-based real-time PCR for the presence of the mcr-1 gene. In total 402 isolates (79.8% of colistin resistant isolates harboured the mcr-1 gene. The prevalence was depending on the food production chain. The highest prevalence was detected in the turkey food chain (10.7%, followed by broilers (5.6%. A low prevalence was determined in pigs, veal calves and laying hens. The mcr-1 was not detected in beef cattle, beef and dairy products in all years investigated. In conclusion, TaqMan based real-time PCR provides a fast and accurate tool for detection of mcr-1 gene. The overall detection rate of 3.8% for mcr-1 among all E. coli isolates tested is due to high prevalence of mcr-1 in poultry production chains. More epidemiological studies of other European countries are urgently needed to assess German prevalence data.
Khalid Ahmed Al-Anazi
Full Text Available Acinetobacter baumannii (A. baumannii is a Gram-negative, strictly aerobic, non-fermentative coccobacillus which is widely distributed in nature. Recently, it has emerged as a major cause of health care-associated infections in addition to its capacity to cause community acquired infections. Risk factors for A. baumannii infections and bacteremia in recipients of hematopoietic stem cell transplantation include: severe underlying illness such as hematological malignancy, prolonged use of broad-spectrum antibiotics, invasive instrumentation such as central venous catheters or endotracheal intubation, colonization of respiratory, gastrointestinal or urinary tracts in addition to severe immunosuppression caused by using corticosteroids for treating graft versus host disease. The organism causes a wide spectrum of clinical manifestations, but serious complications such as bacteremia, septic shock, ventilator-associated pneumonia, extensive soft tissue necrosis and rapidly progressive systemic infections that ultimately lead to multiorgan failure and death are prone to occur in severely immunocompromised hosts. The organism is usually resistant to many antimicrobials including penicillins, cephalosporins, trimethoprim-sulfamethoxazole, almost all flouroquinolones and most of the aminoglycosides. The recently increasing resistance to carbapenems, colistin and polymyxins is alarming. Additionally, there are geographic variations in the resistance patterns and several globally and regionally resistant strains have already been described. Successful management of A.baumannii infections depends upon appropriate utilization of antibiotics and strict application of preventive and infection control measures. In uncomplicated infections, the use of a single active beta-lactam may be justified, while definitive treatment of complicated infections in critically ill individuals may require drug combinations such as colistin and rifampicin or colistin and
de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H
To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.
Runcharoen, Chakkaphan; Raven, Kathy E; Reuter, Sandra; Kallonen, Teemu; Paksanont, Suporn; Thammachote, Jeeranan; Anun, Suthatip; Blane, Beth; Parkhill, Julian; Peacock, Sharon J; Chantratita, Narisara
Tackling multidrug-resistant Escherichia coli requires evidence from One Health studies that capture numerous potential reservoirs in circumscribed geographic areas. We conducted a survey of extended β-lactamase (ESBL)-producing E. coli isolated from patients, canals and livestock wastewater in eastern Thailand between 2014 and 2015, and analyzed isolates using whole genome sequencing. The bacterial collection of 149 isolates consisted of 84 isolates from a single hospital and 65 from the hospital sewer, canals and farm wastewater within a 20 km radius. E. coli ST131 predominated the clinical collection (28.6%), but was uncommon in the environment. Genome-based comparison of E. coli from infected patients and their immediate environment indicated low genetic similarity overall between the two, although three clinical-environmental isolate pairs differed by ≤ 5 single nucleotide polymorphisms. Thai E. coli isolates were dispersed throughout a phylogenetic tree containing a global E. coli collection. All Thai ESBL-positive E. coli isolates were multidrug resistant, including high rates of resistance to tobramycin (77.2%), gentamicin (77.2%), ciprofloxacin (67.8%) and trimethoprim (68.5%). ESBL was encoded by six different CTX-M elements and SHV-12. Three isolates from clinical samples (n = 2) or a hospital sewer (n = 1) were resistant to the carbapenem drugs (encoded by NDM-1, NDM-5 or GES-5), and three isolates (clinical (n = 1) and canal water (n = 2)) were resistant to colistin (encoded by mcr-1); no isolates were resistant to both carbapenems and colistin. Tackling ESBL-producing E. coli in this setting will be challenging based on widespread distribution, but the low prevalence of resistance to carbapenems and colistin suggests that efforts are now required to prevent these from becoming ubiquitous.
Full Text Available Background Nosocomial infections are one of the health problems of modern societies, which are rising with unusual organisms. Acintobacter, which is the main cause of nosocomial infections such as pneumonia and nosocomial pneumonia, is caused by mechanical ventilation. Acinetobacter species are becoming resistant to antibiotics. One the most important agent of nosocomial infections with high mortality is infections by Acinetobacter baumannii which is Gram- negative opportunistic Coccobacilli. Treatment in these infections is difficult and sometimes impossible, due to multidrug resistance in strains isolated from nosocomial infections. Objectives The aim of the current study was to evaluate antibiotic resistance in A. baumannii isolates Khatam-Al-Anbia Hospital, Tehran, Iran. Methods In this cross-sectional study 100 of Acintobacter baumannii were isolated from hospitalized patients during 2013-2015 in Khatam-Al-Anbia hospital in Tehran. In this study samples of A. baumannii isolated from trachea, blood, urine, sputum and wound samples of patients bedridden in Intensive care unit (ICU wards. Antimicrobial susceptibility and minimum inhibitory concentration (MIC were determined by E-test methods. We used descriptive statistics to analyze the data by using SPSS 21 software. Results A total of 100 A. baumannii were isolated from clinical samples. The organism was resistant to rifampicin (46%, gentamicin (67%, meropenem (100%, piperacilin (98%, colistin (0%, and ceftazidin (96%. Conclusions The antibiotic resistance against most of the antibiotics especially meropenem is very high in this study. Moreover, colistin was most effective antibiotic to be used in A. baumannii infections. Colistin is the best choices for treatment of Acinetobacter.
Zanini, S F; Silva-Angulo, A B; Rosenthal, A; Rodrigo, D; Martínez, A
The aim of this study was to evaluate the antibiotic susceptibility of Listeria innocua (L. innocua) and Listeria monocytogenes (L. monocytogenes) cells in the presence of citral and carvacrol at sublethal concentrations in an agar medium. The presence of terpenes in the L. monocytogenes and L. innocua culture medium provided a reduction in the minimal inhibitory concentration (MIC) of all the antibiotics tested. These effects were dependent on the concentration of terpenes present in the culture medium. The combination of citral and carvacrol potentiated antibiotic activity by reducing the MIC values of bacitracin and colistin from 32.0 and 128.0 μg ml⁻¹ to 1.0 and 2.0 μg ml⁻¹, respectively. Thus, both Listeria species became more susceptible to these drugs. In this way, the colistin and bacitracin resistance of L. monocytogenes and L. innocua was reversed in the presence of terpenes. Results obtained in this study show that the phytochemicals citral and carvacrol potentiate antibiotic activity, reducing the MIC values of cultured L. monocytogenes and L. innocua. Phytochemicals citral and carvacrol potentiate antibiotic activity of erythromycin, bacitracin and colistin by reducing the MIC values of cultured Listeria monocytogenes and Listeria innocua. This effect in reducing the MIC values of the antibiotics tested in both micro-organisms was increased when natural antimicrobials were combined. This finding indicated that the combination among terpenes and antibiotic may contribute in reducing the required dosage of antibiotics due to the possible effect of terpenes on permeation barrier of the micro-organism cell membrane. © 2014 The Society for Applied Microbiology.
Srijan, Apichai; Margulieux, Katie R; Ruekit, Sirigade; Snesrud, Erik; Maybank, Rosslyn; Serichantalergs, Oralak; Kormanee, Rosarin; Sukhchat, Prawet; Sriyabhaya, Jossin; Hinkle, Mary; Crawford, John M; McGann, Patrick; Swierczewski, Brett E
Multidrug-resistant Klebsiella pneumoniae strains are one of the most prevalent causes of nosocomial infections and pose an increasingly dangerous public health threat. The lack of remaining treatment options has resulted in the utilization of older drug classes, including colistin. As a drug of last resort, the discovery of plasmid-mediated colistin resistance by mcr-1 denotes the potential development of pandrug-resistant bacterial pathogens. To address the emergence of the mcr-1 gene, 118 gram-negative Enterobacteriaceae isolated from clinical samples collected at Queen Sirikit Naval Hospital in Chonburi, Thailand were screened for colistin resistance using automated antimicrobial susceptibility testing and conventional PCR screening. Two K. pneumoniae strains, QS17-0029 and QS17-0161, were positive for mcr-1, and both isolates were sequenced to closure using short- and long-read whole-genome sequencing. QS17-0029 carried 16 antibiotic resistance genes in addition to mcr-1, including 2 carbapenemases, bla NDM-1 and bla OXA-232 . QS17-0161 carried 13 antibiotic resistance genes in addition to mcr-1, including the extended-spectrum β-lactamase bla CTX-M-55 . Both isolates carried multiple plasmids, but mcr-1 was located alone on highly similar 33.9 Kb IncX4 plasmids in both isolates. The IncX4 plasmid shared considerable homology to other mcr-1-containing IncX4 plasmids. This is the first report of a clinical K. pneumoniae strain from Thailand carrying mcr-1 as well as the first strain to simultaneously carry mcr-1 and multiple carbapenemase genes (QS17-0029). The identification and characterization of these isolates serves to highlight the urgent need for continued surveillance and intervention in Southeast Asia, where extensively drug-resistant pathogens are being increasingly identified in hospital-associated infections.
Schneider-Futschik, Elena K; Paulin, Olivia K A; Hoyer, Daniel; Roberts, Kade D; Ziogas, James; Baker, Mark A; Karas, John; Li, Jian; Velkov, Tony
The mucoid biofilm mode of growth of Pseudomonas aeruginosa ( P. aeruginosa) in the lungs of cystic fibrosis patients makes eradication of infections with antibiotic therapy very difficult. The lipopeptide antibiotics polymyxin B and colistin are currently the last-resort therapies for infections caused by multidrug-resistant P. aeruginosa. In the present study, we investigated the antibacterial activity of a series of polymyxin lipopeptides (polymyxin B, colistin, FADDI-003, octapeptin A 3 , and polymyxin A 2 ) against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa cystic fibrosis isolates grown under planktonic or biofilm conditions in artificial sputum and their interactions with sputum component biomolecules. In sputum media under planktonic conditions, the lipopeptides FADDI-003 and octapeptin A 3 displayed very promising activity against the polymyxin-resistant isolate FADDI-PA066 (polymyxin B minimum inhibitory concentration (MIC) = 32 mg/L), while retaining their activity against the polymyxin-sensitive strains FADDI-PA021 (polymyxin B MIC = 1 mg/L) and FADDI-PA020 (polymyxin B MIC = 2 mg/L). Polymyxin A 2 was only effective against the polymyxin-sensitive isolates. However, under biofilm growth conditions, the hydrophobic lipopeptide FADDI-003 was inactive compared to the more hydrophilic lipopeptides, octapeptin A 3 , polymyxin A 2 , polymyxin B, and colistin. Transmission electron micrographs revealed octapeptin A 3 caused reduction in the cell numbers in biofilm as well as biofilm disruption/"antibiofilm" activity. We therefore assessed the interactions of the lipopeptides with the component sputum biomolecules, mucin, deoxyribonucleic acid (DNA), surfactant, F-actin, lipopolysaccharide, and phospholipids. We observed the general trend that sputum biomolecules reduce lipopeptide antibacterial activity. Collectively, our data suggests that, in the airways, lipopeptide binding to component sputum biomolecules may reduce
Elena, Alan; Cejas, Daniela; Magariños, Francisco; Jewtuchowicz, Virginia; Facente, Andrea; Gutkind, Gabriel; Di Conza, José; Radice, Marcela
Ten IMP-8-producing Escherichia coli isolates were recovered from the surveillance cultures of a neonatal intensive care unit, of which eight were clonally related. A 168.2-kb- bla IMP-8 plasmid was fully sequenced, and it corresponded to the recently described IncA/C1-ST13. This plasmid was detected in all isolates, even in those no clonally related. One unrelated isolate was also resistant to colistin and positive for mcr-1. This marker was located in a 62.7-kb-IncI2 plasmid, which was also fully sequenced. Copyright © 2018 American Society for Microbiology.
Mahfoud, Maysa; Al Najjar, Mona; Hamzeh, Abdul Rezzak
Pseudomonas aeruginosa represents a serious clinical challenge due to its frequent involvement in nosocomial infections and its tendency towards multidrug resistance. This study uncovered antibiotic susceptibility patterns in 177 isolates from inpatients in three key hospitals in Aleppo, the largest city in Syria. Exceptionally low susceptibility to most routinely used antibiotics was uncovered; resistance to ciprofloxacin and gentamicin was 64.9% and 70.3%, respectively. Contrarily, susceptibility to colistin was the highest (89.1%). Multidrug resistance was rife, found at a rate of 53.67% among studied P. aeruginosa isolates.
We describe a case of a 34 year-old, male, with history of lung adenocarcinoma and distal esophagus adenocarcinoma. Was surgically proposed to eso-gastrectomy and eso-gastrostomy. Due the partial dehiscence of the anastomosis, it was placed an endoluminal prosthesis. Three weeks later, it was found an esophageal orifice and a pulmonary abscess due carbapenem resistant klebsiella pneumoniae. He was started on tigecycline, colistine and amphotericin B. However, there wasn’t any improvement, and the patient died on 45th day of his admission. Discussion: Timely microbiological diagnosis, the use of new and old antibiotics and cirurgical intervention appeared to be valuable in managing of this patients.
Gutiérrez, C B; Píriz, S; Vadillo, S; Rodríguez Ferri, E F
Minimal inhibitory concentration of 42 antimicrobial agents was determined against 57 field strains of Actinobacillus pleuropneumoniae isolated from pigs in Spain. Penicillins, aminoglycosides, and tetracyclines had irregular activity; ticarcillin, tobramycin, and doxycycline were the most active of each group, respectively. Macrolides, vancomycin, dapsone, and tiamulin, to which strains had high rate of resistance, were almost ineffective. Thiamphenicol, colistin, rifampin, fosfomycin, mupirocin, and metronidazole had good activity, with resistance ranging between 0 and 8.8%. Finally, cephalosporins (except cephalexin) and quinolones (especially ciprofloxacin, enrofloxacin, and sparfloxacin) were the most active antibiotics against A pleuropneumoniae.
Gutiérrez Martin, C B; Rodríguez Ferri, E F
The minimal inhibitory concentrations (MICs) of 42 antimicrobial agents were determined against 59 strains of Pasteurella multocida subspecies multocida, all isolated from swine lungs with lesions indicative of pneumonia. Penicillins (except cloxacillin), aminoglycosides, tetracyclines, erythromycin, josamycin, thiamphenicol, colistin, rifampin and mupirocin showed good activities, with ranging resistance between 0 and 6.8%. Higher resistance was observed for spiramycin and fosfomycin. Tylosin, vancomycin, metronidazole, dapsone and tiamulin, to which strains showed high rates of resistance, were ineffective. Cephalosporins (especially the third-generation cephalosporins) and quinolones (especially the fluorinated quinolones) were the most effective antimicrobial agents against P. multocida subsp. multocida strains and they might be of value for in vivo use.
colistin, nystatin, trimethoprim , and streptomycin sulfate) was as described (91). Generation of antibodies Affinity-purified rabbit polyclonal... determined empirically: AbHV2 linear (0.87-1.2 µg/mL), AbSV linear (2.2 µg/mL), Ab4L linear (2.4 µg/ml), and AbHV2 cyclic (1:100) and AbSV cyclic (1...killing of the target strains in the absence of added antibody as determined by Garvin 44 et al. (59). For testing Opa loop-specific antibodies
Giamarellou, Helen; Kanellakopoulou, Kyriaki
Based on the worldwide prevalence of multidrug-resistant strains of Pseudomas aeruginosa and the fact that no newer antipseudomonal agents are available, this article aims to investigate therapeutic solutions for combating infections caused by P aeruginosa, including multidrug-resistant strains. The article focuses mainly on colistin, the re-emerging old antibiotic that possesses prominent antipseudomonal activity in vitro and on doripenem, a newer carbapenem that seems to be close to its global marketing. Regarding older antipseudomonal antibiotics that have been reviewed extensively, only newer aspects on their use are considered in this article.
Hansen, C.R.; Pressler, T.; Høiby, Niels
BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF-patients inte......BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF......-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non......-mucoid or mucoid phenotype. RESULTS: 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up...
Viehman, J. Alexander; Nguyen, Minh-Hong; Doi, Yohei
Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Due to various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant, or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii. PMID:25091170
Kim, Dae Hun; Ko, Kwan Soo
To investigate pmrCAB sequence divergence in 5 species of Acinetobacter baumannii complex, a total of 80 isolates from a Korean hospital were explored. We evaluated nucleotide and amino acid polymorphisms of pmrCAB operon, and phylogenetic trees were constructed for each gene of prmCAB operon. Colistin and polymyxin B susceptibility was determined for all isolates, and multilocus sequence typing was also performed for A. baumannii isolates. Our results showed that each species of A. baumannii complex has divergent pmrCAB operon sequences. We identified a distinct pmrCAB allele allied with Acinetobacter nosocomialis in gene trees. Different grouping in each gene tree suggests sporadic recombination or emergence of pmrCAB genes among Acinetobacter species. Sequence polymorphisms among Acinetobacter species might not be associated with colistin resistance. We revealed that a distinct pmrCAB allele may be widespread across the continents such as North America and Asia and that sporadic genetic recombination or emergence of pmrCAB genes might occur. Copyright © 2015 Elsevier Inc. All rights reserved.
Makita, Kohei; Goto, Masaki; Ozawa, Manao; Kawanishi, Michiko; Koike, Ryoji; Asai, Tetsuo; Tamura, Yutaka
The objective of this study was to investigate the association between antimicrobial agent use and antimicrobial resistance in Escherichia coli isolated from healthy pigs using data from 2004 to 2007 in the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM). Fecal E. coli isolates from 250 pigs (one isolate each from a pig per farm) were examined for antimicrobial resistance. Information on the use of antimicrobials within preceding 6 months and types of farms recorded in JVARM was collected and statistically analyzed against the resistance patterns. In the univariate analysis, associations between both therapeutic and feed additive use of antimicrobials, and resistance to dihydrostreptomycin, gentamicin, kanamycin, ampicillin, cefazolin, ceftiofur, oxytetracycline, chloramphenicol, trimethoprim, nalidixic acid, enrofloxacin, colistin, and bicozamycin, and husbandry factors were investigated. In multivariable analysis, generalized estimating equations were used to control geographical intraclass correlation. Confounding for structurally unrelated associations was tested using generalized linear models. The results suggested direct and cross selections in the associations between use of aminoglycosides in reproduction farms and resistance to kanamycin, use of tetracyclines in larger farms and resistance to oxytetracycline, use of beta-lactams and resistance to ampicillin, use of phenicols and resistance to chloramphenicol, and use of fluoroquinolones and resistance to nalidixic acid and enrofloxacin. Coselection was suggested in the use of tetracyclines and chloramphenicol resistance. The associations between use of beta-lactams and dihydrostreptomycin resistance, use of macrolides and ampicillin and oxytetracycline resistance, and use of colistin and kanamycin resistance were significant, but were confounded by the simultaneous use of homologous antimicrobials.
Neeraj Kumar Tulara
Full Text Available Urinary tract infection (UTI is a common and painful human illness that, unfortunately not responsive to commonly used antibiotics in current practice. The role of fosfomycin and nitrofurantoin in the era of growing bacteria resistance has been widely discussed. In this study, we aimed to know the local antimicrobial susceptibilities, fosfomycin and nitrofurantoin susceptibility in particular, for urinary extended-spectrum-beta-lactamase-producing Escherichia coli and Escherichia pneumoniae (ESBL-EC and ESBL-KP isolates in our hospital. We collected 464 urine isolates, including 384 ESBL-EC and 80 ESBL-KP isolates. Of 464 urine isolates culture positive ESBL-UTIs, EC caused 384 (82.75%, followed by Klebsiella in 80 (17.24%. Carbapenems and Colistin seems to remain as the first line therapy for the majority of ESBL-UTIs in the local setting. Colistin and fosfomycin remains the most sensitive antibiotic while nitrofurantoin still preserves the good sensitivity against ESBL and found to be an only oral sensitive antibiotic.
Ni, Wentao; Shao, Xiaodi; Di, Xiuzhen; Cui, Junchang; Wang, Rui; Liu, Youning
In order to provide preliminary guidance for rational antibiotic combination therapy in the clinic, a systematic review and meta-analysis was performed to evaluate the in vitro synergistic activity of polymyxins combined with other antibiotics against Acinetobacter baumannii. An extensive literature search was undertaken without restriction according to region, publication type or language. All available in vitro synergy tests on antibiotic combinations consisting of polymyxins were included. The primary outcome assessed was the in vitro activity of combination therapy on bacterial kill or inhibition. In total, 70 published studies and 31 conference proceedings reporting testing of polymyxins in combination with 11 classes consisting of 28 antibiotic types against 1484 A. baumannii strains were included in the analysis. In time-kill studies, high in vitro synergy and bactericidal activity were found for polymyxins combined with several antibiotic classes such as carbapenems and glycopeptides. Carbapenems or rifampicin combination could efficiently suppress the development of colistin resistance and displayed a >50% synergy rate against colistin-resistant strains. Synergy rates of chequerboard microdilution and Etest methods in most antibiotic combinations were generally lower than those of time-kill assays. The benefits of these antibiotic combinations should be further demonstrated by well-designed clinical studies. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Caires, C. S. A.; Leal, C. R. B.; Rodrigues, A. C. S.; Lima, A. R.; Silva, C. M.; Ramos, C. A. N.; Chang, M. R.; Arruda, E. J.; Oliveira, S. L.; Nascimento, V. A.; Caires, A. R. L.
The emergence of plasmid-mediated colistin resistance in Enterobacteriaceae, mostly in Escherichia coli due to the mcr-1 gene, has revealed the need to develop alternative approaches in treating mcr-1 positive bacterial infections. This is because colistin is a broad-spectrum antibiotic and one of the ‘last-resort’ antibiotics for multidrug resistant bacteria. The present study evaluated for the first time, to the best of our knowledge, the efficacy of photoinactivation processes to kill a known mcr-1 positive E. coli strain. Eosin methylene-blue (EMB) was investigated as a photoantimicrobial agent for inhibiting the growth of a mcr-1 positive E. coli strain obtained from a patient with a diabetic foot infection. The photoantimicrobial activity of EMB was also tested in a non-multidrug resistant E. coli strain. The photoinactivation process was tested using light doses in the 30-45 J cm-2 range provided by a LED device emitting at 625 nm. Our findings demonstrate that a mcr-1 positive E. coli strain is susceptible to photoinactivation. The results show that the EMB was successfully photoactivated, regardless of the bacterial multidrug resistance; inactivating the bacterial growth by oxidizing the cells in accordance with the generation of the oxygen reactive species. Our results suggest that bacterial photoinactivation is an alternative and effective approach to kill mcr-1 positive bacteria.
Hitch, Thomas C A; Thomas, Ben J; Friedersdorff, Jessica C A; Ougham, Helen; Creevey, Christopher J
Antibiotic resistance is an increasingly important environmental pollutant with direct consequences for human health. Identification of environmental sources of antibiotic resistance genes (ARGs) makes it possible to follow their evolution and prevent their entry into the clinical setting. ARGs have been found in environmental sources exogenous to the original source and previous studies have shown that these genes are capable of being transferred from livestock to humans. Due to the nature of farming and the slaughter of ruminants for food, humans interact with these animals in close proximity, and for this reason it is important to consider the risks to human health. In this study, we characterised the ARG populations in the ovine rumen, termed the resistome. This was done using the Comprehensive Antibiotic Resistance Database (CARD) to identify the presence of genes conferring resistance to antibiotics within the rumen. Genes were successfully mapped to those that confer resistance to a total of 30 different antibiotics. Daptomycin was identified as the most common antibiotic for which resistance is present, suggesting that ruminants may be a source of daptomycin ARGs. Colistin resistance, conferred by the gene pmrE, was also found to be present within all samples, with an average abundance of 800 counts. Due to the high abundance of some ARGs (against daptomycin) and the presence of rare ARGs (against colistin), we suggest further study and monitoring of the rumen resistome as a possible source of clinically relevant ARGs. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Song, Xuqin; Xie, Jingmeng; Zhang, Meiyu; Zhang, Yingxia; Li, Jiufeng; Huang, Qiwen; He, Limin
A high throughput, reliable and reproducible analysis strategy based on high performance liquid chromatography combined to evaporative light scattering detector (HPLC-ELSD) was developed for simultaneous determination of eight cyclopolypeptide antibiotics including vancomycin, polymyxin B (polymyxin B1 and polymyxin B2), polymyxin E (colistin A and colistin B), teicoplanin, bacitracin A, daptomycin and virginiamycin M1 in animal Feed. Feed samples were extracted with methanol-2% formic acid aqueous solution, followed by a solid-phase extraction step using a HLB cartridge. Under the optimum chromatographic conditions and ELSD parameters, target compounds were separated well on a short column filled with biphenyl stationary phase. The method was developed in accordance with pig complete feed and then extended to detect polypeptide antibiotics in piglet premix, pig feed additive, poultry complete feed and fattening pig premix. The results showed that logarithmic calibration curves of eight analytes were linear (r 2 > 0.99) within the concentration range of 5-200 mg mL -1 . The developed method provided good accuracy and precision for quantification of eight polypeptides in five kinds of feeds with recoveries ranging from 72.0% to 105.4% with relative standard deviations antibiotics in commercial feed. Copyright © 2018 Elsevier B.V. All rights reserved.
Chiang, Wen-Chi; Pamp, Sünje Johanna; Nilsson, Martin
encoding lipopolysaccharide modification enzymes, as well as on the mexAB-oprM, mexCD-oprJ, and muxABC-opmB genes encoding antimicrobial efflux pumps, but does not depend on the mexPQ-opmE efflux pump genes. Development of chlorhexidine-tolerant subpopulations was found to depend on the mexCD-oprJ genes......, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes. Our data suggest that the active subpopulation in P. aeruginosa......-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes...
Wang, Yang; Zhang, Rongmin; Li, Jiyun; Wu, Zuowei; Yin, Wenjuan; Schwarz, Stefan; Tyrrell, Jonathan M; Zheng, Yongjun; Wang, Shaolin; Shen, Zhangqi; Liu, Zhihai; Liu, Jianye; Lei, Lei; Li, Mei; Zhang, Qidi; Wu, Congming; Zhang, Qijing; Wu, Yongning; Walsh, Timothy R; Shen, Jianzhong
By 2030, the global population will be 8.5 billion, placing pressure on international poultry production, of which China is a key producer 1 . From April 2017, China will implement the withdrawal of colistin as a growth promoter, removing over 8,000 tonnes per year from the Chinese farming sector 2 . To understand the impact of banning colistin and the epidemiology of multi-drug-resistant (MDR) Escherichia coli (using bla NDM and mcr-1 as marker genes), we sampled poultry, dogs, sewage, wild birds and flies. Here, we show that mcr-1, but not bla NDM , is prevalent in hatcheries, but bla NDM quickly contaminates flocks through dogs, flies and wild birds. We also screened samples directly for resistance genes to understand the true breadth and depth of the environmental and animal resistome. Direct sample testing for bla NDM and mcr-1 in hatcheries, commercial farms, a slaughterhouse and supermarkets revealed considerably higher levels of positive samples than the bla NDM - and mcr-1-positive E. coli, indicating a substantial segment of unseen resistome-a phenomenon we have termed the 'phantom resistome'. Whole-genome sequencing identified common bla NDM -positive E. coli shared among farms, flies, dogs and farmers, providing direct evidence of carbapenem-resistant E. coli transmission and environmental contamination.
A. N. Kuzovlev
Full Text Available Nosocomial pneumonia is the second most common nosocomial infection in critical care units and most common in ALV patients (9—27%. The purpose of this literature review is to discuss the latest domestic and foreign body of evidence concerning the use of inhaled antibiotics в critical care. Search for domestic publications (literature reviews, observation studies, double blind randomized studies was carried out in elibrary.ru database, for foreign — in PubMed. Database for the period of yrs. 2005—2017. The following search enquiries were used: «inhaled antibiotics», «nosocomial pneumonia», «inhaled tobramycin», «inhaled colistin». The analysis includes 67 publications of yrs. 2007—2017 and 1 publication of yr. 2000. The literature review includes drug descriptions, contemporary capabilities of inhaled antibiotic therapy for nosocomial pneumonia, the advantages and drawbacks of this method of treatment. Special attention is focused on the use of inhaled aminoglycosides and inhaled colistin during nosocomial pneumonia in critical care units.
Isolamento e caracterização de Pseudomonas maltophilia (Hugh & Ryschenkow, 1960 de material clínico humano, na cidade do Rio de Janeiro Isolating and characterization of Pseudomonas maltophilia (Hugh & Ryschenkow, 1960 from human clinical specimens, in Rio de Janeiro, Guanabara, Brazil
Altair A. Zebral
Full Text Available Os autores estudaram as propriedades morfo-bioquímicas e a sensibilidade às substâncias antimicrobianas, de uma nova e rara espécie de Pseudomonas, a Pseudomonas maltophilia (Hugh & Ryschenkow, 1960, isolada de secração vaginal. Como características marcantes, dentre mais de 65 testadas, as amostras estudadas mostraram ser: oxidase negativa e lisina descarboxilase positiva; produziram desoxiribonuclease e um pigmento escuro que se difunde no meio; atacaram oxidativamente a maltose tanto em meio complexo nitrogenado como em meio de Hugh & Leifson e hidrolisaram a esculina. As amostras foram sensíveis ao cloranfenicol, gentamicina, kanamicina, colistin e gabromicina.The authors have studied the morpho-biochemical properties and the sensibility at antimicrobial drugs, of specie of Pseudomonas, the Pseudomonas maltophilia, (Hugh & Ryschenkow, 1960, isolated from vaginal secretion. Since important characteristics among more of sixty-five tested, the strains studied show to be: oxidase negative and lysine decarboxylase positive; to present deoxyrononuclease activity and produced a diffusible brown pigment: acid was produced by oxidation of maltose as much in nitrogenous complex medium as in Hugh & Leifson medium and they hydrolise the esculin. the strains was sensible, for the colistin chloranfenicol, gabromycin, gentamycin and nalidix acid.
Full Text Available Macleaya cordata extract is of great scientific and practical interest to researchers, due to its antimicrobial and anti-inflammatory responses within experimental animals. This study was designed to determine the diarrhea score and innate immunity of growing piglets after they had received Macleaya cordata extract supplements. A total of 240 growing pigs were randomly assigned to one of three dietary treatments, with 8 replicates per treatment and 10 piglets per replicate. All pigs received a basal diet containing similar amounts of nutrients. The three treatments were a control (no additive, an antibiotic (200 mg/kg colistin, and the Macleaya cordata extract supplement group (40 mg/kg Macleaya cordata extract. The diarrhea score was calculated after D 28. The jejunal samples were obtained from five piglets selected randomly from each treatment on D 28. In comparison with the control group, the dietary Macleaya cordata extract and colistin group demonstrated a substantially decreased diarrhea score. The introduction of Macleaya cordata extract supplements to the diet significantly increased volumes of ZO-1 and claudin-1, particularly in comparison with the pigs in the control group (P<0.05. The findings indicate that Macleaya cordata extract does enhance intestinal barrier function in growing piglets and that it could be used as a viable substitute for antibiotics.
Full Text Available In order to evaluate differences in resistance patterns of Escherichia coli isolated from different parts of sheep digestive tract, the intestinal tracts of 24 sheep were sampled at various locations (duode-num, jejunum, caecum, colon and rectum after slaughter. Samples were cultured on MacConkey agar and obtained colonies were confirmed as E. coli based on the biochemical tests results. Isolates were tested for antimicrobial agent susceptibility to 10 antibiotics (colistin, gentamicin, oxytetracycline, trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid, enrofloxacin, ampicillin, cephotaxime, neomycin and florfenicol, using disc diffusion method. The tested E. coli resistant to colistin, ampicillin and amoxicillin-clavulanic acid were isolated more frequently from large intestine (rectum than from small intestine (duodenum (P<0.05. In conclusion, antimicrobial resistance pattern of generic E. coli inhabiting the intestinal tract of sheep depends on sampling location, which should be considered in interpreting the results of antimicrobial resistance tests of E. coli isolated from the faecal samples and generalising results to bacteria colonised in other parts of the digestive tract
Dohar, J E; Kenna, M A; Wadowsky, R M
The choice of antimicrobial agents used to treat Pseudomonas aeruginosa infections of the ear is quite empiric. Yet in spite of this, very little has been published examining susceptibility patterns of aural isolates of P. aeruginosa. Recently, increasing concern has emerged over the development of resistance to many of the commonly used ototopical preparations with activity against P. aeruginosa. This concern stems from the fact that these preparations have been in use for a long time, and P. aeruginosa is known to develop resistance fairly readily. We prospectively studied the susceptibilities of aural isolates of P. aeruginosa in 231 consecutive children who were seen in the outpatient Pediatric Otolaryngology Department at Children's Hospital of Pittsburgh during the years 1992 and 1993. The agents tested included neomycin, polymyxin B, colistin, and norfloxacin. We found that only 17.8% of the isolates were sensitive to neomycin, as opposed to > 95% for each of the other agents tested (polymyxin B, 99.6%; colistin, 97.4%; and norfloxacin, 98.3%). This difference proved to be statistically significant (p < 0.05). Given the concern of aminoglycoside-induced ototoxicity and the high rate of neomycin resistance, we believe that further investigation of other alternative ototopic agents with activity against P. aeruginosa is warranted.
Dinh, Aurélien; Davido, Benjamin; Calin, Ruxandra; Paquereau, Julie; Duran, Clara; Bouchand, Frédérique; Phé, Véronique; Chartier-Kastler, Emmanuel; Rottman, Martin; Salomon, Jérôme; Plésiat, Patrick; Potron, Anaïs
Urinary tract infections (UTI) are a major public health problem among spinal cord injury (SCI) patients. They frequently involve multidrug-resistant (MDR) bacteria. Ceftolozane/tazobactam (C/T) is a novel antibiotic combination approved for complicated intra-abdominal and UTI caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for complicated febrile UTI occurring among SCI patients with neurogenic bladder due to MDR Pseudomonas aeruginosa (PSA). We describe the case of a 35-year-old man with SCI due to multiple sclerosis, with a neurogenic bladder necessitating a bilateral nephrostomy and double J catheter, who developed a febrile UTI due to a MDR PSA, which was susceptible only to amikacin and colistin. Because of this MDR phenotype and the underlying kidney disease, a 1000 mg (1000 mg per 500 mg) dose of C/T was given as monotherapy every 8 h for 7 days, after 3 days of colistin and amikacin. Thanks to this treatment, the patient had a favorable outcome with no clinical signs of UTI or positive urine culture up to 1 month after diagnosis. C/T seems to be an effective and safe therapeutic option for febrile UTI due to MDR PSA in SCI patients with neurogenic bladder, even when administered in monotherapy for 10 days.
de Man, Tom J B; Lutgring, Joseph D; Lonsway, David R; Anderson, Karen F; Kiehlbauch, Julia A; Chen, Lei; Walters, Maroya Spalding; Sjölund-Karlsson, Maria; Rasheed, J Kamile; Kallen, Alexander; Halpin, Alison Laufer
Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae , nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. The isolate harbored four known beta-lactamase genes, including plasmid-mediated bla NDM-1 and bla CMY-6 , as well as chromosomal bla CTX-M-15 and bla SHV-28 , which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline. IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide
Chan, Wai-Sing; Au, Chun-Hang; Ho, Dona N; Chan, Tsun-Leung; Ma, Edmond Shiu-Kwan; Tang, Bone Siu-Fai
Human fecal carriage of Enterobacteriaceae possessing mobilized colistin resistance genes (mcr-1 and mcr-2) remains obscure in Hong Kong. As part of routine surveillance on emerging antibiotic resistance, we conducted a prospective study on this topic in a regional hospital in Hong Kong. From October 31 to November 25, 2016, all fecal specimens submitted for routine analysis were included in this surveillance study. These comprised 672 consecutive routine fecal specimens collected from 616 individuals. Fecal specimens were screened for colistin-resistant Enterobacteriaceae by culture-based method, and the presence of mcr-1 and mcr-2 genes in resistant isolates was identified by polymerase chain reaction and Sanger sequencing. Whole genome sequencing (WGS) of mcr-1-possessing Escherichia coli strains was facilitated using Illumina® MiSeq® followed by sequence analysis with appropriate bioinformatics tools. Fourteen mcr-1-positive E. coli strains were isolated from 14 separate individuals (2.08% of total fecal specimens), with 9 of them being asymptomatic, healthy clients coming for health assessment. No mcr-2-possessing Enterobacteriaceae was identified. Colistin minimum inhibitory concentrations of these mcr-1-positive isolates ranged from 2 to 4 μg/mL. All these isolates were susceptible to carbapenems with 2 being extended spectrum β-lactamase producers. WGS data revealed that these isolates belonged to at least 12 different sequence types (STs) and possessed diversified plasmid replicons, virulence and acquired antibiotic resistance genes. Further study on an E. coli ST201 strain (Pasteur scheme) revealed coexistence of 47,818-bp IncP-1 and 33,309-bp IncX4 types of mcr-1 plasmids, which was a combination of stability and high transmissibility. To the best of our knowledge, this is the first study on human fecal carriage of Enterobacteriaceae possessing mcr-1 and mcr-2 genes in Hong Kong. Our data further revealed asymptomatic carriage of mcr-1-possessing
Development, validation and application of an ultra high performance liquid chromatographic-tandem mass spectrometric method for the simultaneous detection and quantification of five different classes of veterinary antibiotics in swine manure.
Van den Meersche, Tina; Van Pamel, Els; Van Poucke, Christof; Herman, Lieve; Heyndrickx, Marc; Rasschaert, Geertrui; Daeseleire, Els
In this study, a fast, simple and selective ultra high performance liquid chromatographic-tandem mass spectrometric (UHPLC-MS/MS) method for the simultaneous detection and quantification of colistin, sulfadiazine, trimethoprim, doxycycline, oxytetracycline and ceftiofur and for the detection of tylosin A in swine manure was developed and validated. First, a simple extraction procedure with acetonitrile and 6% trichloroacetic acid was carried out. Second, the supernatant was evaporated and the pellet was reconstituted in 1 ml of water/acetonitrile (80/20) and 0.1% formic acid. Extracts were filtered and analyzed by UHPLC-MS/MS on a Kinetex C18 column using gradient elution. The method developed was validated according to the criteria of Commission Decision 2002/657/EC. Recovery percentages varied between 94% and 106%, repeatability percentages were within the range of 1.7-9.2% and the intralaboratory reproducibility varied between 2.8% and 9.3% for all compounds, except for tylosin A for which more variation was observed resulting in a higher measurement uncertainty. The limit of detection and limit of quantification varied between 1.1 and 20.2 and between 3.5 and 67.3 μg/kg, respectively. This method was used to determine the presence and concentration of the seven antibiotic residues in swine manure sampled from ten different manure pits on farms where the selected antibiotics were used. A link was found between the antibiotics used and detected, except for ceftiofur which is injected at low doses and degraded readily in swine manure and was therefore not recovered in any of the samples. To the best of our knowledge, this is the first method available for the simultaneous extraction and quantification of colistin with other antibiotic classes. Additionally, colistin was never extracted from swine manure before. Another innovative aspect of this method is the simultaneous detection and quantification of five different classes of antibiotic residues in swine manure
Landman, David; Singh, Manisha; El-Imad, Badiaa; Miller, Ezra; Win, Thida; Quale, John
The in vitro activity of BAL30072 was assessed against clinical isolates from NYC hospitals, including isolates from a citywide surveillance study and a collection of isolates with well-characterised resistance mechanisms. BAL30072 was the most active β-lactam against Pseudomonas aeruginosa (MIC50/90, 0.25/1 μg/mL), Acinetobacter baumannii (MIC50/90, 4/>64 μg/mL) and KPC-possessing Klebsiella pneumoniae (MIC50/90, 4/>64 μg/mL). Combining BAL30072 with meropenem resulted in a ≥ 4-fold decrease in the BAL30072 MIC90 both for A. baumannii and K. pneumoniae. For isolates with a BAL30072 MIC>4 μg/mL, addition of a sub-MIC concentration of colistin resulted in a four-fold decrease in the BAL30072 MIC in 44% of P. aeruginosa, 82% of A. baumannii and 23% of K. pneumoniae. Using sub-MIC concentrations, BAL30072 plus colistin was bactericidal against 4 of 11 isolates in time-kill studies. BAL30072 MICs were frequently lower for P. aeruginosa and K. pneumoniae when tested using Mueller-Hinton agar versus Iso-Sensitest agar or Mueller-Hinton broth. Against the well-characterised isolates, reduced susceptibility to BAL30072 correlated with mexA and mexX expression (P. aeruginosa), adeB expression (A. baumannii) and presence of SHV-type ESBLs (A. baumannii and K. pneumoniae). BAL30072 shows promising activity against contemporary Gram-negatives, including MDR P. aeruginosa, A. baumannii and K. pneumoniae. Enhanced activity was often present when BAL30072 was combined with meropenem or colistin. BAL30072 MICs were influenced by the testing method, particularly for P. aeruginosa and K. pneumoniae. Further in vivo studies are warranted to determine the potential clinical utility of BAL30072 alone and combined with other agents. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Altair A. Zebral
Full Text Available No presente trabalho, os autores estudaram as propriedades morfo-bioquímicas e a sinsibilidade aos antibióticos de 19 amostras de bactérias dos gêneros Mima e Herellea isoladas de material clínico e identificadas como Mima polymorpha variedade oxidans, Mima polymorpha e Herellea vaginicola. No estudo bioquímico observou-se que Herellea vaginicola foi oxidase negativa e em meio complexo nitrogenado, consistentemente ataca a glicose, galactose, manose, arabinose, xilose, lactose a 10% e irregularmente ataca a ramnose e a celobiose; em base sintética nitrogenada, além das atividades citadas, consistentemente produziu ácido a partir da lactose. Mima polymopha foi oxidase negativa, não apresentando atividade glicidolítica, quer em meio complexo nitrogenado, quer em base sintética nitrogenada. Mima polymorpha var. oxidans, foi oxidase positiva, não revelando nenhuma atividade glicidolítica. Herellea vaginicola e Mima polymorpha mostraram grande sensibilidade à gabromicina, knamicina, neomicina, colistin, sendo que a última também foi muito sensível ao cloranfenicol e rovamicina. Mima polymorpha var. oxidans, apresentou grande sensibilidade à knamicina, neomicina, colistin, cloranfenicol e wintomylon. A sensibilidade das amostras a 1 a 0,1 unidade de penicilina/ml, nas condições ensaiadas no presente trabalho, não foi absoluta, como a observada por Baumann, Doudoroff & Stanier (1968a que permitisse uma separação entre amostras oxidase positiva e negativa ou uma diferenciação dentro do grupo das bactérias oxidase positiva.The authors studied the morpho-biochemical characteristics and antibiotic sensitivity of 19 strains of bacteria isolated from clinical specimens and identifyed as Mima polymorpha var. oxidans, Mima polymorpha and Herellea vaginicola. The biochemical study indicated Herellea vaginicola to be oxidase negative and in complex nitrogenous media effetively utilize glucose, galactose, manose, arabinose, xylose, 10
Maraki, Sofia; Vardakas, Konstantinos Z; Samonis, George; Perdikis, Dimitrios; Mavromanolaki, Viktoria Eirini; Kofteridis, Diamantis P; Falagas, Matthew E
To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.
Ahn, Chulsoo; Syed, Alveena; Hu, Fupin; O’Hara, Jessica A.; Rivera, Jesabel I.; Doi, Yohei
Microbiological data regarding KPC-producing Enterobacter spp. are scarce. In this study, 11 unique KPC-producing Enterobacter isolates were identified among 44 ertapenem-non-susceptible Enterobacter isolates collected between 2009 and 2013 at a hospital system in Western Pennsylvania. All cases were healthcare-associated and occurred in medically complex patients. While pulsed-field gel electrophoresis (PFGE) showed diverse restriction patterns overall, multilocus sequence typing (MLST) identified Enterobacter cloacae isolates with sequence types (STs) 93 and 171 from two hospitals each. The levels of carbapenem minimum inhibitory concentrations were highly variable. All isolates remained susceptible to colistin, tigecycline, and the majority to amikacin and doxycycline. A blaKPC-carrying IncN plasmid conferring trimethoprim-sulfamethoxazole resistance was identified in three of the isolates. Spread of blaKPC in Enterobacter spp. appears to be due to a combination of plasmid-mediated and clonal processes. PMID:25053203
Vorland, L H; Osbakk, S A; Perstølen, T; Ulvatne, H; Rekdal, O; Svendsen, J S; Gutteberg, T J
The antimicrobial peptide, lactoferricin, can be generated upon gastric pepsin cleavage of lactoferrin. We have examined the interaction of lactoferricin of bovine origin, Lf-cin B, with the antibiotics penicillin G, vancomycin, gentamicin, colistin, D-cycloserine and erythromycin against E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923. We demonstrated synergism between Lf-cin B and erythromycin against E. coli, and partial synergism between Lf-cin B and penicillin G, vancomycin and gentamicin against E. coli. Only penicillin G acted in partial synergism with Lf-cin B against S. aureus. Lf-cin B antagonized vancomycin and gentamicin against S. aureus in low concentration. We conclude that Lf-cin B may facilitate the uptake of antibiotics across the cell envelope.
Tan, Sean Yang-Yi; Chua, Song Lin; Liu, Yang
, comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU...... within a 1-month interval. Multilocus sequence typing indicates that these two isolates belonged to ST208. The A. baumannii 53264 strain gained colistin resistance compared with the 48055 strain and became an EDR strain. Genome sequencing indicates that A. baumannii 53264 and 48055 have almost identical...... genomes—61 single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii 53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135 contigs, with a total length of 4,049,562 bp with 39...
Dalsgaard, A.; Bjergskov, T.; Jeppesen, V.F.
A total of 3,555 metric tonnes of warm water shrimp were imported into Denmark from December 1994 to July 1995. V. cholerae O1 was not detected in any of the 748 samples analyzed. Non-Ol V. cholerae was found in a single (0.1%) cooked frozen shrimp product and in five (0.7%) raw frozen products......, all originating from shrimp produced in aquaculture. Six isolated strains agglutinated in polyvalent O antisera, but did not agglutinate in Ogawa or Inaba antisera. The six strains were resistant to colistin and sulfisoxazole; three strains also showed resistance to ampicillin. None of the strains...... contained plasmids or genes encoding cholera toxin (CT) or heat-stable enterotoxin (NAG-ST), The absence of V. cholerae O1 and the low number of samples containing CT and NAG-ST negative non-Ol strains in imported shrimp suggest that I! cholerae in such products may not constitute a public health problem....
Potter, Robert F; D'Souza, Alaric W; Dantas, Gautam
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Harini H. and Sumathi B.R.
Full Text Available The study was undertaken to find out the incidence of subclinical mastitis (SCM and to assess the antibiotic sensitivity pattern of the causative organisms in lactating cows in and around Kanakapura taluk, Ramanagara district of Karnataka state. The prevalence of subclinical mastitis was assessed by the results of 3 different screening tests and bacteriological evaluation was done for the milk samples that were found positive. The predominant bacterial isolates recovered were Staphylococcus aureus (58% and Escherichia coli (23.5% followed by Staphylococcus epidermidis (8%, Streptococcus sp. (5.5%, Klebsiella sp. (3% and Bacillus sp. (2%. The in vitro antibiogram studies of bacterial isolates revealed higher sensitivity for ciprofloxacin (89%, ofloxacin (85%, enrofloxacin (82%, gentamicin (80% and chloramphenicol (75%, resistant to colistin, neomycin, streptomycin, penicillin and tetracycline. [Vet. World 2011; 4(8.000: 358-359
The present-day availability and usage of established and new antibacterial drugs approved for clinical and therapeutic purposes in food-producing animals and poultry in the United States and Europe were compared. Presently, 42 such drugs are approved in Europe, 13 of which were approved since Dec 31, 1974. In the United States, 17 such drugs are currently approved, only four were approved since Dec 31, 1974. Most drug products approved in Europe contain two or more antibacterial agents, whereas most of the products approved in the United States are single drug entities. Drugs approved in Europe but not in the United States include sulfonamide and trimethoprim combinations, nafcillin, oxacillin, metampicillin, cephoxazole, cephalonium, cephacetrile, cephalexin, gentamicin, rifamycin SV, nifuroquine, tiamulin, chloramphenicol, colistin, and polymyxin B. Pharmacologic and clinical features of several of these drugs are briefly described.
Gutiérrez, C B; Rodríguez Barbosa, J I; Tascón, R I; Costa, L; Riera, P; Rodríguez Ferri, E F
Seventy-one isolates of Actinobacillus pleuropneumoniae isolated from the lungs of pigs in outbreaks of pleuropneumonia in Spain were serotyped by indirect haemagglutination. Serotype 4 (42.2 per cent), serotype 7 (22.5 per cent) and serotype 2 (12.8 per cent) were predominant, whereas serotypes 1, 3, 6, 8, 9, 12 and untypable isolates were present only in small numbers. Serotypes 1, 2, 4 and 7 originated mainly from cases of acute pleuropneumonia, whereas serotypes 3, 6, 8, 9 and 12 were associated with chronically infected herds. The susceptibility of the isolates to 20 antimicrobial agents was determined by agar disc diffusion. Most were susceptible to cefuroxime, cefaclor, cefazolin, kanamycin, tobramycin, gentamicin, oxolinic acid, ciprofloxacin, enoxacin, thiamphenicol, colistin and trimethoprim/sulphamethoxazole. Marked resistance was found with amoxicillin, ticarcillin, oxytetracycline, doxycycline and metronidazole. Rifampicin, fosfomycin and tiamulin were the agents most effective against the isolates tested.
Varga, J; Fodor, L; Makrai, L
The biochemical characteristics and antibiotic susceptibility of 12 Ornithobacterium rhinotracheale strains isolated from chickens and turkeys suffering from respiratory clinical signs and the survival of some isolates on egg-shell and within chicken eggs during hatching were examined. All O. rhinotracheale strains showed typical biochemical characteristics. Among the 16 drugs examined, penicillin G, ampicillin (MICs ranging from tiamulin (MICs varied from colistin) or not at all (apramycin, spectinomycin, polymyxin B). At 37 degrees C, O. rhinotracheale did not survive on egg-shell for more than 24 hours, while upon inoculation into embryonated chicken eggs it killed embryos by the ninth day, and from the 14th day post-inoculation no O. rhinotracheale could be cultured from the eggs at all. These results suggest that O. rhinotracheale is not transmitted via eggs during hatching.
Sugimoto, C; Isayama, Y; Kashiwazaki, M; Mitani, K
The minimal inhibitory concentrations of 31 antimicrobial agents were determined for 99 isolates of Haemophilus equigenitalis by the agar dilution method. All the isolates showed good susceptibility to 26 antimicrobial agents tests, minimal inhibitory concentrations of which were less than 3.13 micrograms/ml for more than 90% of the isolates. Of these agents, 4 macrolides (erythromycin, oleandomycin, kitasamycin, tylosin), 3 tetracyclines (tetracycline, chlortetracycline, oxytetracycline), 1 peptide (colistin), 1 penicillin (ampicillin) and 1 pleuromutilin (tiamulin) were the most active agents, showing a minimal inhibitory concentration of less than 0.39 micrograms/ml for more than 90% of the isolates. The growth of more than 90% of the isolates was not inhibited by 800 micrograms/ml of streptomycin.
Potter, Robert F.; D’Souza, Alaric W.; Dantas, Gautam
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. PMID:27912842
Dalsgaard, A.; Mazur, J.; Dalsgaard, Inger
. The strain contained two plasmids, in contrast to other O139 strains, which normally do not contain plasmids. The characteristics of the strain led to further agglutination testing with other antisera that are not commercially available, and the strain was found to agglutinate O155 antiserum in repeated...... was isolated from imported raw frozen shrimp. The toxigenicity of the strain was analyzed, and the results of a polymerase chain reaction showed that the V. cholerae strain did not contain the virulence genes ctx, tcp9, and zot, which are normally found in V. cholerae O1 and O139. The strain was resistant...... to colistin and spectinomycin. The high susceptibility of the strain to antimicrobial agents was confirmed by the lack of an SXT element, a self-transmissible, chromosomal genetic element that is normally present in O139 strains and encodes resistance to sulfonamides, trimethoprim, and streptomycin...
Vellend, H.; Tuttle, S. A.; Barza, M.; Weinstein, L.; Picciolo, G. L.; Chappelle, E. W.
Luciferase assay for adenosine triphosphate (ATP) was optimized for pure bacteria in broth in order to evaluate if changes in bacterial ATP content could be used as a rapid measure of antibiotic effect on microorganisms. Broth cultures of log phase bacteria were incubated at 310 K (37 C) for 2.5 hours at antimicrobial concentrations which resulted in the best discrimination between sensitive and resistant strains. Eighty-seven strains of 11 bacterial species were studied for their susceptibility to 12 commonly used antimicrobial agents: ampicillin, Penicillin G, nafcillin, carbenicillin, cephalothin, tetracycline, erythromycin, clindamycin, gentamicin, nitrofurantoin, colistin, and chloramplenicol. The major advantage of the ATP system over existing methods of rapid microbial susceptibility testing is that the assay can be made specific for bacterial ATP.
Full Text Available Fourteen antibacterial agents belonging to 9 different groups of antibiotics viz. aminoglycosides, cephalosporins, nitrofurantoin, fluroquinolones, chloramphenicol, sulphonamides, tetracyclines, penicillin and polymixin were used for in vitro sensitivity testing of Aeromonas hydrophila isolated from fifteen samples of chicken collected from retail shops in Mhow city. The sensitivity (100% was attributed to ciprofloxacin, cefuroxime, ceftriaxone, cephotaxime, chloramphenicol, gentamycin, kanamycin, nitrofurantoin, nalidixic acid and ofloxacin followed by oxytetracycline (50%. All the isolates were resistant to ampicillin and colistin antibiotics. That means, none of the isolates were found to be sensitive for penicillin and polymixin group of antibiotics. Multiple drug resistance was also observed in all A. hydrophila isolates. Out of total isolates, 100% were resistant to two antimicrobial drugs and 50% to three drugs. [Vet. World 2009; 2(1.000: 31-32
Chua, Song Lin; Tan, Sean Yang-Yi; Rybtke, Morten Theil
Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger which controls the life styles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes...... a planktonic lifestyle. Here, we used expression of different reporters to show that planktonic cells (PCells), biofilm cells (BCells) and cells dispersed from biofilms (DCells) had distinct intracellular c-di-GMP levels. Proteomics analysis showed that the low intracellular c-di-GMP level of DCells induced...... the expression of proteins required for the virulence and development of antimicrobial peptide resistance in P. aeruginosa. In accordance, P. aeruginosa cells with low c-di-GMP levels were found to be more resistant to colistin than P. aeruginosa cells with high c-di-GMP levels. This contradicts the current...
Mortensen, Ninell Pollas
changes in the fraction of individual bacteria and bacteria undergoing proliferation, and decrease of cell length of mother and daughter cells. The results indicated that colistin arrested the bacterial growth just after septum formation. Furthermore did the morphology change from a smooth bacterial......Atomic Force Microscopy (AFM) is unique in the aspect of studying living biological sample under physiological conditions. AFM was invented in 1986 by Binnig and Gerber and began in the early 1990’s to be implemented in life science. AFM can give a detailed three dimensional image of an intact cell......, but also be used to examine the nanomechanical properties on single cell level. These qualities make AFM a powerful tool in biology and can be used to examine both morphological and nanomechanical response to various liquids environments, such as osmotic pressure, but also the effects of e.g. antibiotic...
Bäuerlein, A.; Ackermann, S.; Parlesak, Alexandr
The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... Escherichia coli K12, probiotic E. coli Nissle, EPEC) induced basolateral production of TNF-alpha, IFN-gamma, IL 6, 8, and 10. Gram-positive probiotics (Lactobacillus spp. and Bifidobacterium spp.) had virtually no effect. In addition, commensals (Enterococcus faecalis, Bacteroides vulgatus) and food...... (polymyxin, colistin) completely abrogated transepithelial activation of leukocytes. Enterobacteriaceae-type endotoxin is a crucial factor in transepithelial stimulation of leukocytes, regardless of whether it is produced by probiotics or other bacteria. Hence, transepithelial stimulation ofleukocytes...
Baeuerlein, Annette; Ackermann, Stefanie; Parlesak, Alexandr
The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... Escherichia coli K12, probiotic E. coli Nissle, EPEC) induced basolateral production of TNF-alpha, IFN-gamma, IL 6, 8, and 10. Gram-positive probiotics (Lactobacillus spp. and Bifidobacterium spp.) had virtually no effect. In addition, commensals (Enterococcus faecalis, Bacteroides vulgatus) and food...... (polymyxin, colistin) completely abrogated transepithelial activation of leukocytes. Enterobacteriaceae-type endotoxin is a crucial factor in transepithelial stimulation of leukocytes, regardless of whether it is produced by probiotics or other bacteria. Hence, transepithelial stimulation of leukocytes...
Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik
Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous, and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs...... for the targets in silico . Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex...... in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin...
Kusdarwati, R.; Rozi; Dinda, N. D.; Nurjanah, I.
Fish suffer, from bacteria, fungi, virus and parasites or by physical ailments. Gurami (Osphronemus gouramy), nila (Oreochromis niloticus), carp (Cyprinus carpio), catfish (Clarias sp.) were the most reported infections caused by Aeromonas are bacterial hemorrhagic septicemia or Motile Aeromonas Septicemia (MAS). Antibiotics are drugs of natural or synthetic origin that have the capacity to kill or to inhibit the growth of micro-organisms included MAS. However, the use of antibiotics in the long term can cause negative impacts, among others, feared the occurrence of bacterial resistance in certain antibiotics. The results showed five of isolates were sensitive to antibiotics of chloramphenicol, gentamycin, oxytetracycline, cefradoxil and nalidixic acid but resistant to vancomycin colistin sulphate, rifampisin, cephalosporin and novobiocin.
Baggesen, Dorte Lau; Aarestrup, Frank Møller
electrophoresis (PFGE) using the restriction enzyme Xba I, Overall, 66 per cent of the 670 isolates were sensitive to all the antimicrobial agents tested. Eleven isolates of S typhimurium were resistant to ampicillin, streptomycin and tetracycline and also resistant to other antibiotics in different resistance...... patterns. Seven different multiresistant clones were identified, The most common clones were four isolates of DT104 and three isolates of DT193, TWO Of the three S typhimurium DT104 from 1994 and 1995 were sensitive to all the antimicrobials tested whereas the remaining isolate from 1994 was resistant......A total of 670 isolates of Salmonella enterica were isolated from Danish pig herds, phage typed and tested for susceptibility to amoxycillin + clavulanate, ampicillin, colistin, enrofloxacin, gentamicin, neomycin, spectinomycin, streptomycin, tetracyclines, and trimethoprim + sulphadiazine. S...
Oguntibeju, O.O.; Nwobu, R.A.U.
Objective: To determine the prevalence of Pseudomonas aeruginosa in post-operative wound infection. Results: Out of the 60 bacterial isolates found in post-operative wound infection, 20 (33.3%) were Pseudomonas aeruginosa, followed by Staphylococcus aureus 13(21.7%), Klebsiella species 10(16.7%), Escherichia coli 7(11.7%), Atypical coliform 4(6.7%), Proteus species 4(6.7%), Streptococcus pyogenes 1(1.7%) and Enterococcus faecalis 1(1.7%) in the order. Pseudomonas aeruginosa infections was higher in female than male, ratio 3:2 and was found more among young and elderly debilitated patients. The in vitro sensitivity pattern of 20 isolates of Pseudomonas aeruginosa showed colistin (100%), gentamicin (75%), streptomycin (30%), and tetracycline (10%). Conclusion: The role of Pseudomonas aeruginosa as an agent of nosocomial infection is re-emphasised. (author)
Hunt, D E; Jones, J V; Dowell, V R
Bacteroides gingivalis has been implicated in various forms of periodontal disease and may be responsible for other diseases in humans. The role of B. gingivalis in disease has been difficult to assess, because it is inhibited by most selective media commonly used by clinical laboratories to aid in isolating gram-negative, nonsporeforming anaerobes. We have developed a new medium, Bacteroides gingivalis agar, which contains bacitracin, colistin, and nalidixic acid as selective agents. This medium allowed B. gingivalis to be isolated from oral specimens with little difficulty and also allowed B. gingivalis to be isolated from phenotypically similar Bacteroides species, such as B. asaccharolyticus and B. endodontalis, with which it can easily be confused.
Rahmatallah, Naoufal; El Rhaffouli, Hicham; Lahlou Amine, Idriss; Sekhsokh, Yassine; Fassi Fihri, Ouafaa; El Houadfi, Mohammed
Monitoring the use of antibacterial agents in food-producing animals is crucial in order to reduce antimicrobial resistance, selection and dissemination of resistant bacterial strains, and drug residues in the animal food products. The broiler production sector is considered a great consumer of antibacterials and incriminated in the rise of antimicrobial resistance level in zoonotic bacterial pathogens such as Escherichia coli, Salmonella and Campylobacter. Following recommendations from the OIE and WHO, a survey was conducted about the use and consumption of several antibacterial agents in Moroccan broiler flocks. More than 5 million broilers were randomly surveyed at the prescriber level, that is, via the veterinary clinics involved in their health management. The results showed that 93% of the flocks received at least one antibacterial treatment of minimum 3 days duration. Enrofloxacin, colistin and trimethoprim/sulphonamides were the most used antibacterials followed by oxytetracycline, florfenicol and amoxicillin. Oxytetracycline, enrofloxacin and colistin were overdosed in most of the administration, while amoxicillin and the combination of trimethoprim/sulphonamides were under-dosed. The total amount of antibacterial consumed in the survey was 63.48 mg/kg and the Animal Level of Exposure to Antimicrobials (ALEA) was 94.45%. The reasons for this frequent use were related mainly to the poor quality of broiler production management. Chicks and animal feed provided to producers were of variable quality. Management of rearing stock density was often poor and biosecurity inadequate, and broilers were challenged by a high prevalence of infectious diseases. © 2018 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.
Al-Agamy, Mohamed H; Jeannot, Katy; El-Mahdy, Taghrid S; Shibl, Atef M; Kattan, Wael; Plésiat, Patrick; Courvalin, Patrice
This study was conducted to investigate the molecular epidemiology of resistance in Acinetobacter baumannii isolates collected at a hospital in Riyadh, Saudi Arabia, from January through December 2010. Twenty-seven A. baumannii were highly resistant (MIC 90 > 256 μg/ml) to ceftazidime, cefepime, and aztreonam. Imipenem resistance was seen in 24 isolates, of which 18 had an minimum inhibitory concentration (MIC) >32 μg/mL. Ciprofloxacin, gentamicin, and amikacin resistance was found in 93%, 52%, and 37% of all the isolates, respectively. Moreover, 8 (30%) isolates showed colistin resistance, and 15 (56%) were found to have MICs ≥4 μg/mL for tigecycline. The frequency of ADC, GES-1, GES-11, and GES-5 were 96.3% (n = 26), 18.5% (n = 5), 11% (n = 3), and 3.7% (n = 1), respectively. OXA-23 was found in 63% (n = 17) of the isolates; ISAba1 was found upstream of OXA-23 in 16. OXA-24/40 was detected in only one strain. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) analysis revealed that the 27 strains were distributed in 8 sequence types (STs) and 16 clonal pulsotypes (A-P). Five singleton STs were identified, including ST15 and ST113-ST116. The emergence of multidrug-resistant A. baumannii is becoming a major concern in Saudi Arabia. Metallo-β-lactamases have no role in carbapenem resistance in this collection. The spread of OXA-23 in our strains occurred across different STs and pulsotypes, unlike what has been observed in many other countries. PFGE typing was more discriminatory than MLST. The high frequency of colistin and tigecycline resistance found in the isolates calls for continuous monitoring. This study describes the first identification of GES-5 conferring carbapenem resistance in A. baumannii.
Mavroidi, Angeliki; Katsiari, Maria; Palla, Eleftheria; Likousi, Sofia; Roussou, Zoi; Nikolaou, Charikleia; Platsouka, Evangelia D
A rapid increase was observed in the incidence of extensively drug-resistant Acinetobacter baumannii (XDR Aba) isolates in a Greek hospital during 2014. To investigate the causes of this rise, the antimicrobial resistance profiles of all carbapenem-resistant (CARB-R) Aba isolates recovered during 2014-2015 were determined. Selected XDR Aba isolates (n = 13) were characterized by molecular methods. XDR Aba (48 isolates) represented 21.4% of the 224 CARB-R Aba recovered during the study period. The 13 selected XDR Aba isolates were positive for the blaOXA-23, the intrinsic blaOXA-51, and the adeB gene of the AdeABC efflux pump, and all belonged to the 3LST ST101, corresponding to the international clone II. Three bloodstream isolates possessed two amino acid substitutions (A138T+A226V) in the deduced amino acid sequences of the pmrB gene, which may be implicated in colistin resistance. This study demonstrates that this clone still evolves by obtaining an ever-increasing arsenal of antibiotic resistance mechanisms. The clinical characteristics of the intensive care unit (ICU) patients with XDR Aba were reviewed retrospectively. Infected ICU patients with XDR Aba displayed higher death rates compared with infected ICU patients susceptible to colistin and tigecycline CARB-R Aba, although there were no statistically significant differences. Conclusively, continuous surveillance and molecular characterization of XDR Aba, combined with strict infection control measures are mandatory for combating nosocomial infections caused by this organism.
Full Text Available A total of 1666 samples were examined, of which 512 samples of parenchymatous organs of dead or deliberately sacrtificed animals, 60 samples of non-hatched fertilized eggs, 202 samples of feces, 652 samples of cloacal smears, 221 samples of smears from walls of maintenance objects, incubator stations, and transport vehicles, 19 samples of beddings and shavings. The samples originated from poultry farms and which were taken to a laboratory immediately on sampling and sown the same day. A total of 104 strains of Salmonella were isolated: 94 strains from samples of parenchymatous organs of dead chicks, 1 strain from non-hatched eggs, 3 strains from feces samples, 1 strain from samples of cloacal smears, 4 strains from samples of surface smears of maintenance objects and transport vehicles, and 1 strain from samples of beddings and shavings. Serological typization established the presence of the following serovarieties: Salmonella Enteritidis 79 strains, Salmonella Hartford 17 strains, Salmonella Typohimurium 5 strains, Salmonella Mbandaka 2 strains, and Salmonella Glostrup 1 strain. We examined the sensitivity of Salmonella strains to ampicillin, amoxicillin, gentamycin, streptomycin, neomycin, enrofloxacine, norfloxacine, flumequin, erythromycin, lincospectin, colistin, fluorphenicol, and a combination of sulphamethoxasole and trimethoprim. In S. Enteritidis strains, no resistence was established to colistin, fluorphenicol and sulphamethoxasole+trimethoprim, in fact, the sensitivity to these antibiotics and chemotherapeutics was 100%. Prevalence resitence of 0.96%, in only one strain, was established for enrofloxacine. A high prevalence resistence of 33.6% was established for neomycin, while prevalence resistence of 3.86% was established for the related aminoglycozide antibiotic gentamycin. The highest prevalence resistance in S.Hartford strains was established for erythromycin, 15.38%, and streptomycin, 7.6%. Resistence of S. Tyohimurium was
Full Text Available Objectives: Device-associated nosocomial infections (DANIs have a major impact on patient morbidity and mortality. Our study aimed to determine the distribution rate of DANIs and causative agents and patterns of antibiotic resistance in the trauma-surgical intensive care unit (ICU. Methods: Our study was conducted at Abusalim Trauma Hospital in Tripoli, Libya. All devices associated with nosocomial infections, including central venous catheters (CVC, endotracheal tubes (ETT, Foley’s urinary catheters, chest tubes, nasogastric tubes (NGT, and tracheostomy tubes, were removed aseptically and examined for Gram-negative bacteria (GNB. Results: During a one-year study period, 363 patients were hospitalized; the overall mortality rate was 29%. A total of 79 DANIs were identified, the most common site of infection was ETT (39.2%, followed by urinary catheters (19%, NGTs (18%, tracheostomy tubes (11%, CVCs (10%, and chest tubes (3%. The most frequently isolated organisms were Klebsiella pneumonia, Acinetobacter baumannii, and Pseudomonas aeruginosa (30%, 20%, and 14%, respectively. Extremely high resistance rates were observed among GNB to ampicillin (99%, cefuroxime (95%, amoxicillin-clavulante (92%, and nitrofurantoin (91%. Lower levels of resistance were exhibited to amikacin (38%, imipenem (38%, and colistin (29%. About 39% of the isolates were defined as multi-drug resistant (MDR. Overall, extended spectrum β-lactmase producers were expressed in 39% of isolates mainly among K. pneumonia (88%. A. baumannii isolates exhibited extremely high levels of resistance to all antibiotics except colistin (100% sensitive. In addition, 56.3% of A. baumannii isolates were found to be MDR. P. aeruginosa isolates showed 46%–55% effectiveness to anti-pseudomonas antibiotics. Conclusion: High rates of DANI’s and the emergence of MDR organisms poses a serious threat to patients. There is a need to strengthen infection control within the ICU environment
Full Text Available Abstract Background In a recent multi-centre Italian survey (2003–2004, conducted in 45 laboratories throughout Italy with the aim of monitoring microorganisms responsible for severe infections and their antibiotic resistance, Acinetobacter baumannii was isolated from various wards of 9 hospitals as one of the most frequent pathogens. One hundred and seven clinically significant strains of A. baumannii isolates were included in this study to determine the in vitro activity of tigecycline and comparator agents. Methods Tests for the susceptibility to antibiotics were performed by the broth microdilution method as recommended by CLSI guidelines. The following antibiotics were tested: aztreonam, piperacillin/tazobactam, ampicillin/sulbactam, ceftazidime, cefepime, imipenem, meropenem tetracycline, doxycycline, tigecycline, gentamicin, amikacin, ciprofloxacin, colistin, and trimethoprim/sulphametoxazole. The PCR assay was used to determine the presence of OXA, VIM, or IMP genes in the carbapenem resistant strains. Results A. baumannii showed widespread resistance to ceftazidime, ciprofloxacin and aztreonam in more than 90% of the strains; resistance to imipenem and meropenem was 50 and 59% respectively, amikacin and gentamicin were both active against about 30% of the strains and colistin about 99%, with only one strain resistant. By comparison with tetracyclines, tigecycline and doxycycline showed a higher activity. In particular, tigecycline showed a MIC90 value of 2 mg/L and our strains displayed a unimodal distribution of susceptibility being indistinctly active against carbapenem-susceptible and resistant strains, these latter possessed OXA-type variant enzymes. Conclusion In conclusion, tigecycline had a good activity against the MDR A. baumannii strains while maintaining the same MIC90 of 2 mg/L against the carbapenem-resistant strains.
Full Text Available The plasmid-borne colistin-resistant gene mcr-1 has rapidly become a worldwide public health concern. This study aims to determine the host bacterial strains, plasmids, and genetic contexts of mcr-1 in hospital sewage. A 1-ml hospital sewage sample was cultured. Colistin-resistant bacterial colonies were selected on agar plates and were subjected to whole genome sequencing and subsequent analysis. The transfer of mcr-1 between bacterial strains was tested using conjugation. New variants of mcr-1 were cloned to test the impact of variations on the function of mcr-1. Plasmids carrying mcr-1 were retrieved from GenBank for comparison based on concatenated backbone genes. In the sewage sample, we observed that mcr-1 was located in various genetic contexts on the chromosome, or plasmids of four different replicon types (IncHI2, IncI2, IncP, and IncX4, in Klebsiella pneumoniae, Kluyvera spp. and seven Escherichia coli strains of six different sequence types (ST10, ST34, ST48, ST1196, ST7086, and ST7087. We also identified two new variants of mcr-1, mcr-1.4 and mcr-1.7, both of which encode an amino acid variation from mcr-1. mcr-1-carrying IncX4 plasmids, which have a global distribution across the Enterobacteriaceae, are the result of global dissemination of a single common plasmid, while IncI2 mcr-1 plasmids appear to acquire mcr-1 in multiple events. In conclusion, the unprecedented remarkable diversity of species, strains, plasmids, and genetic contexts carrying mcr-1 present in a single sewage sample from a single healthcare site highlights the continued evolution and dynamic transmission of mcr-1 in healthcare-associated environments.
Bassetti, Matteo; Peghin, Maddalena; Pecori, Davide
Multidrug-resistant (MDR) Enterobacteriaceae are often related to the production of extended-spectrum b-lactamases (ESBLs) and carbapenemase-producing Enterobacteriaceae (CRE), and represent an increasing global threat. Recommendations for the therapeutic management of MDR-related infections, however, are mainly derived from retrospective and nonrandomized prospective studies. The aim of this review is to discuss the challenges in the treatment of patients with infections because of MDR Enterobacteriaceae and provide an expert opinion while awaiting for more definitive data. To avoid the selection of carbapenemase-producing Enterobacteriaceae, carbapenem-sparing strategies should be considered. B-lactams/b-lactamase inhibitors, mainly piperacillin-tazobactam, minimum inhibitory concentration (MIC) 16/4mg/ml or less represents the best alternative to carbapenems for the treatment of ESBL-producing strains. Overall, combination therapy may be preferred over monotherapy for CRE. The combination of a carbapenem-containing regimen with colistin or high-dose tigecycline or aminoglycoside can be administered at high-dose prolonged infusion with therapeutic drug monitoring for the treatment of CRE with MIC for meropenem 8-16 mg/l or less. For MIC higher than 8-16 mg/l, the use of meropenem should be avoided and various combination therapies based on the in-vitro susceptibility of antimicrobials (e.g., colistin, high-dose tigecycline, fosfomycin, and aminoglycosides) should be selected. Carbapenem-sparing strategies should be used, when feasible, for ESBL infections. The majority of available nonrandomized studies highlight that combination for CRE seem to offer some therapeutic advantage over monotherapy. Strict infection control measures toward MDR Gram-negative pathogens remain necessary while awaiting for new treatment options.
Increasing proportion of carbapenemase-producing Enterobacteriaceae and emergence of a MCR-1 producer through a multicentric study among hospital-based and private laboratories in Belgium from September to November 2015.
Huang, Te Din; Bogaerts, Pierre; Berhin, Catherine; Hoebeke, Martin; Bauraing, Caroline; Glupczynski, Youri
Carbapenemase-producing Enterobacteriaceae (CPE) strains have been increasingly reported in Belgium. We aimed to determine the proportion of CPE among Enterobacteriaceae isolated from hospitalised patients and community outpatients in Belgium in 2015. For the hospitalised patients, the results were compared to a previous similar survey performed in the same hospitals in 2012. Twenty-four hospital-based and 10 private laboratories collected prospectively 200 non-duplicated Enterobacteriaceae isolates from clinical specimens. All isolates were screened locally by carbapenem disk diffusion using European Committee on Antimicrobial Susceptibility Testing methodology. Putative CPE strains with inhibition zone diameters below the screening breakpoints were referred centrally for confirmation of carbapenemase production. From September to November 2015, we found a proportion of clinical CPE of 0.55% (26/4,705) and of 0.60% (12/1,991) among hospitalised patients and among ambulatory outpatients respectively. Klebsiella pneumoniae (26/38) and OXA-48-like carbapenemase (28/38) were the predominant species and enzyme among CPE. One OXA-48-producing Escherichia coli isolated from a hospital was found carrying plasmid-mediated MCR-1 colistin resistance. Compared with the 2012 survey, we found a significant increased proportion of clinical CPE (0.55% in 2015 vs 0.25% in 2012; p = 0.02) and an increased proportion of hospitals (13/24 in 2015 vs 8/24 in 2012) with at least one CPE detected. The study results confirmed the concerning spread of CPE including a colistin-resistant MCR-1 producer in hospitals and the establishment of CPE in the community in Belgium. This article is copyright of The Authors, 2017.
Jeong, Seok Hoon; Kim, Han Sung; Kim, Jae Seok; Shin, Dong Hoon; Kim, Hyun Soo; Park, Min Jeong; Shin, Saeam; Hong, Jun Sung; Lee, Seung Soon; Song, Wonkeun
The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem because these bacteria are resistant to most antibiotics. CPE remain relatively uncommon in Korea. We report the prevalence, clinical characteristics, and molecular epidemiology of CPE isolates collected from five university hospitals in Korea. Between January and December 2015, 393 non-duplicated isolates that were nonsusceptible to ertapenem were analyzed. Production of carbapenemase, extended-spectrum β-lactamase, and AmpC β-lactamase was determined by genotypic tests. Antimicrobial susceptibility profiles were determined by using an Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC)-2-producing and oxacillinase (OXA)-232-producing Klebsiella pneumoniae isolates was determined by pulsed-field gel electrophoresis (PFGE). Of the 393 isolates tested, 79 (20.1%) were CPE. Of these 79 isolates, 47 (59.5%) harbored the bla(OXA-232) gene while the remaining isolates carried genes bla(KPC-2) (n=27), bla(IMP-1) (n=4), and bla(NDM-1) (n=1). Among the 24 KPC-2 K. pneumoniae isolates from hospital B, 100% were resistant to carbapenems, 8% to colistin, and 0% to tigecycline. Among the 45 OXA-232 K. pneumoniae at hospital C, 95% were resistant to ertapenem, 68% to imipenem, 95% to meropenem, 10% to colistin, and 24% to tigecycline. PFGE analysis revealed a unique pattern for KPC-2 K. pneumoniae and identified 30 isolates belonging to the dominant pulsotypes (PT)1 and PT2 among 41 OXA-232 K. pneumoniae isolates. CPE strains are present in Korea, with the majority of K. pneumoniae isolates producing OXA-232 and KPC-2. The prevalence and predominant genotypes of CPE show hospital-specific differences.
Full Text Available Background: Wound infection is one of the major health problems that are caused and aggravated by the invasion of pathogenic organisms where empiric treatment is routine. Objective: To isolate and identify the bacteria causing wound infection and to determine the antimicrobial susceptibility pattern. Materials and method: A total of 263 wound swab and pus samples were collected during the period of January to December 2012 from Delta Medical College and Hospital, Dhaka, Bangladesh. Swabs from the wound were inoculated on appropriate media and cultured and the isolates were identified by standard procedures as needed. Antimicrobial susceptibility testing was performed by disk diffusion method according to ‘The Clinical Laboratory Standard Institute’ guidelines. Results: In this study 220 bacterial isolates were recovered from 263 samples showing an isolation rate of 83.65%. The predominant bacteria isolated from infected wounds were Staphylococcus aureus 89 (40.45% followed by Escherichia coli 62 (28.18%, Pseudomonas aeruginosa 34 (15.45%, Enterococci 18 (8.18%, Acinetobacter 5 (2.27%, Klebsiella 9 (4.09% and Proteus 3 (3.36%. Staphylococcus aureus was sensitive to linezolid (94.38%, fusidic acid (91.01%, vancomycin (87.64%, amikacin (74.15% and gentamicin (73.03%. Among the Gram negative isolates Escherichia coli was predominant and showed sensitivity to imipenem (93.54% amikacin (83.87% colistin (53.22% and piperacillin and tazobactum (53.22% and pseudomonas showed sensitivity to amikacin (73.52%, imipenem (70.58% and colistin (70.58%. Conclusion: Staphylococcus aureus was the most frequently isolated pathogen from wound swab and the antibiotic sensitivity pattern of various isolates help to assist the clinician in appropriate selection of empirical antibiotics against wound infection.
M. Cem Şirin
Full Text Available Objective: The aim of this study was to determine the antibiotic resistance profiles of Pseudomonas aeruginosa and Acinetobacter baumannii strains isolated from patients in our hospital intensive care units (ICUs between the years 2011-2014 and to investigate the changes of these profiles over the years. Methods: Identification and antibiotic susceptibility testing of the strains were performed by automated system. Cefoperazone-sulbactam and tigecycline susceptibility was determined by disk diffusion method. Imipenem, meropenem and colistin resistance was confirmed by E-test method. Chi-square and Fisher's exact test were used to compare the antibiotic susceptibilities statistically. Results: The highest resistance rates were determined for imipenem (50.2%, meropenem (51.9% and piperacillin-tazobactam (64.0% in P. aeruginosa strains (n=722. The changes in the rates of antibiotic resistance were not statistically significant in P. aeruginosa strains between the years 2011 and 2014. The decrease in gentamicin, amikacin and trimethoprim-sulfamethoxazole resistance and the increase in cefoperazone-sulbactam and tigecycline resistance was found to be statistically significant in A. baumannii strains (n=1044 between the years 2011 and 2014. The increase in imipenem and meropenem resistance was found to be statistically significant between the years 2012 and 2013. Piperacillin-tazobactam, ceftazidime, cefepime, imipenem and meropenem resistances in A. baumannii strains were found to be over 95% in all the years. Colistin was found to be the most effective antimicrobial agent for both bacteria. Conclusion: The determination of considerably high antibiotic resistance rates in P. aeruginosa and A. baumannii strains isolated from our hospital ICUs has indicated that rational antibiotic use policies and more effective infection control programs should be applied along with monitoring the antibiotic susceptibility profiles constantly. J Clin Exp Invest 2015
Sonnevend, Ágnes; Ghazawi, Akela; Hashmey, Rayhan; Haidermota, Aliasgher; Girgis, Safinaz; Alfaresi, Mubarak; Omar, Mohammed; Paterson, David L; Zowawi, Hosam M; Pál, Tibor
The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant K. pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, IS Ecp1 -driven bla OXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene, indicating that it was responsible for colistin resistance. bla NDM-5 was located within a resistance island of an approximately 100-kb IncFII plasmid carrying ermB , mph (A), bla TEM-1B , rmtB , bla NDM-5 , sul1 , aadA2 , and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including bla NDM-5 , had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the bla NDM-5 -carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally. Copyright © 2017 American Society for Microbiology.
Full Text Available Introduction: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA is an important and growing issue in the care of patients with cystic fibrosis (CF, and a major cause of morbidity and mortality. Objective: The objective of the study was to describe the frequency of MDR-PA recovered from the lower respiratory samples of pediatric and adult CF patients, and its antibiotic resistance pattern to commonly used antimicrobial agents including β-lactams, aminoglycosides, and fluoroquinolones. Materials and Methods: The lower respiratory isolates of P. aeruginosa were obtained from inpatients and outpatients CF clinics from a tertiary care teaching hospital for the period from October 2014 to September 2015. The identification and antimicrobial susceptibility for all the isolates were performed by using the BD Phoenix™ and E-test in compliance with Clinical and Laboratory Standards Institute (CLSI guidelines. Results: A total of 61 P. aeruginosa samples were isolated from thirty CF patients from twenty families. Twelve sputum samples were positive for MDR-PA (seven nonmucoid and five mucoid isolates from five CF patients (five families with moderate-to-very severe lung disease given MDR-PA frequency of 19.7%. The median age of the study group was 20 (range 10–30 years. Three CF patients were on chronic inhaled tobramycin and two on nebulized colistin. The antimicrobial patterns of isolates MDR-PA showed the highest rate of resistance toward each gentamycin, amikacin, and cefepime (100%, followed by 91.7% to ciprofloxacin, 75% to tobramycin, 58.3% to meropenem, and 50% to piperacillin-tazobactam. None of the isolates were resistant to colistin during the study period. Conclusion: The study results emphasize that the emergence of a significant problem in the clinical isolates of P. aeruginosa in CF patients that dictate appropriate attention to the antibiotic management after proper surveillance.
Tsai, Chin-Chuan; Lin, Chi-Shiuan; Hsu, Chun-Ru; Chang, Chiu-Ming; Chang, I-Wei; Lin, Li-Wei; Hung, Chih-Hsin; Wang, Jiun-Ling
No animal model studies have been conducted in which the efficacy of herbal compounds has been tested against multidrug-resistant Acinetobacter baumannii infections. Very few antibiotics are available for the treatment of pulmonary infections caused by extensively drug-resistant Acinetobacter baumannii (XDRAB). To find alternative treatments, traditional Chinese herbs were screened for their antimicrobial potential. The present study screened 30 herbs that are traditionally used in Taiwan and that are commonly prescribed for heat clearing and detoxification. The herbs with antibacterial activities were analysed by disc diffusion assays, time-kill assays and a murine lung infection model. Of the 30 herbs tested, only Scutellaria barbata demonstrated 100% in vitro activity against XDRAB. Furthermore, we compared the antibacterial effect of the S. barbata extract with that of colistin, and the S. barbata extract showed better antibacterial effect. In the XDRAB pneumonia murine model, we compared the antimicrobial effects of the orally administered S. barbata extract (200 mg/kg, every 24 h), the intratracheally administered colistin (75,000 U/kg, every 12 h), and the control group. The bacterial load in the lungs of the treatment group that received the oral S. barbata extract showed a significant decrease in comparison to that in the lungs of the control group. In addition, histopathological examinations also revealed better resolution of perivascular, peribronchial, and alveolar inflammation in the oral S. barbata extract-treated group. Our in vitro and in vivo data from the animal model support the use of S. barbata as an alternate drug to treat XDRAB pulmonary infections. However, detailed animal studies and clinical trials are necessary to establish the clinical utility of S. barbata in treating XDRAB pulmonary infections.
Lee, Yangsoon; Kim, Bong-Soo; Chun, Jongsik; Yong, Ji Hyun; Lee, Yeong Seon; Yoo, Jung Sik; Yong, Dongeun; Hong, Seong Geun; D'Souza, Roshan; Thomson, Kenneth S; Lee, Kyungwon; Chong, Yunsop
We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC-) producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR) K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including bla KPC-2, bla SHV-11, bla TEM-169, and bla OXA-9. MP14 also possessed aac(6'-)Ib, aadA2, and aph(3'-)Ia as aminoglycoside resistance-encoding genes, mph(A) for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains) isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.
Full Text Available We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC- producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including blaKPC-2, blaSHV-11, blaTEM-169, and blaOXA-9. MP14 also possessed aac(6′-Ib, aadA2, and aph(3′-Ia as aminoglycoside resistance-encoding genes, mph(A for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.
Ehrmann, E; Jolivet-Gougeon, A; Bonnaure-Mallet, M; Fosse, T
In oral microbiome, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of fastidious Capnocytophaga species. The performances of six culture media (blood agar, chocolate blood agar, VCAT medium, CAPE medium, bacitracin chocolate blood agar and VK medium) were compared with literature data concerning five other media (FAA, LB, TSBV, CapR and TBBP media). To understand variable growth on selective media, the MICs of each antimicrobial agent contained in this different media (colistin, kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, vancomycin, aztreonam and bacitracin) were determined for all Capnocytophaga species. Overall, VCAT medium (Columbia, 10% cooked horse blood, polyvitaminic supplement, 3·75 mg l(-1) of colistin, 1·5 mg l(-1) of trimethoprim, 1 mg l(-1) of vancomycin and 0·5 mg l(-1) of amphotericin B, Oxoid, France) was the more efficient selective medium, with regard to the detection of Capnocytophaga species from oral samples (P culture, a simple blood agar allowed the growth of all Capnocytophaga species. Nonetheless, in oral samples, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of Capnocytophaga species. The demonstrated superiority of VCAT medium made its use essential for the optimal detection of this bacterial genus. This work showed that extreme caution should be exercised when reporting the isolation of Capnocytophaga species from oral polymicrobial samples, because the culture medium is a determining factor. © 2013 The Society for Applied Microbiology.
Daniel De Vos
Full Text Available Multidrug resistant Acinetobacter baumannii and its closely related species A. pittii and A. nosocomialis, all members of the Acinetobacter calcoaceticus-baumannii (Acb complex, are a major cause of hospital acquired infection. In the burn wound center of the Queen Astrid military hospital in Brussels, 48 patients were colonized or infected with Acb complex over a 52-month period. We report the molecular epidemiology of these organisms, their clinical impact and infection control measures taken. A representative set of 157 Acb complex isolates was analyzed using repetitive sequence-based PCR (rep-PCR (DiversiLab and a multiplex PCR targeting OXA-51-like and OXA-23-like genes. We identified 31 rep-PCR genotypes (strains. Representatives of each rep-type were identified to species by rpoB sequence analysis: 13 types to A. baumannii, 10 to A. pittii, and 3 to A. nosocomialis. It was assumed that isolates that belonged to the same rep-type also belonged to the same species. Thus, 83.4% of all isolates were identified to A. baumannii, 9.6% to A. pittii and 4.5% to A. nosocomialis. We observed 12 extensively drug resistant Acb strains (10 A. baumannii and 2 A. nosocomialis, all carbapenem-non-susceptible/colistin-susceptible and imported into the burn wound center through patients injured in North Africa. The two most prevalent rep-types 12 and 13 harbored an OXA-23-like gene. Multilocus sequence typing allocated them to clonal complex 1 corresponding to EU (international clone I. Both strains caused consecutive outbreaks, interspersed with periods of apparent eradication. Patients infected with carbapenem resistant A. baumannii were successfully treated with colistin/rifampicin. Extensive infection control measures were required to eradicate the organisms. Acinetobacter infection and colonization was not associated with increased attributable mortality.
Brennan-Krohn, Thea; Truelson, Katherine A; Smith, Kenneth P; Kirby, James E
Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights
The Cytos 2 experiment was performed aboard Salyut 7 in order to test the antibiotic sensitivity of bacteria cultivated in vitro in space. An increase of the Minimal Inhibitory Concentration (MIC) in the inflight cultures (i.e., an increase of the antibiotic resistance) was observed. Complementary studies of the ultrastructure showed a thickening of the cell envelope. In order to confirm the results of the Cytos 2 experiment, we performed the ANTIBIO experiment during the D1 mission to try to differentiate, by means of the 1 g centrifuge in the Biorack, between the biological effects of cosmic rays and those caused by microgravity conditions. The originality of this experiment was in the fact that it was designed to test the antibiotic sensitivity of bacteria cultivated in vitro during the orbital phase of the flight. The results show an increase in resistance to Colistin in in-flight bacteria. The MIC is practically double in the in-flight cultures. A cell count of living bacteria in the cultures containing the different Colistin concentrations showed a significant difference between the cultures developed during space flight and the ground based cultures. The comparison between the 1 g and 0 g in-flight cultures show similar behavior for the two sets. Nevertheless, a small difference between the two sets of ground based control cultures was noted. The cultures developed on the ground centrifuge (1.4 g) present a slight decrease in comparison with the cultures developed in the static rack (1 g). In order to approach the mechanisms of the increase of antibiotic resistance on bacteria cultivated in vitro in space, we have proposed the study on penetration of antibiotics in bacterial cells in space conditions. This experiment was selected for the International Microgravity Laboratory 1 (IML-1) mission.
Bilocq, Florence; Jennes, Serge; Verbeken, Gilbert; Rose, Thomas; Keersebilck, Elkana; Bosmans, Petra; Pieters, Thierry; Hing, Mony; Heuninckx, Walter; De Pauw, Frank; Soentjens, Patrick; Merabishvili, Maia; Deschaght, Pieter; Vaneechoutte, Mario; Bogaerts, Pierre; Glupczynski, Youri; Pot, Bruno; van der Reijden, Tanny J.; Dijkshoorn, Lenie
Multidrug resistant Acinetobacter baumannii and its closely related species A. pittii and A. nosocomialis, all members of the Acinetobacter calcoaceticus-baumannii (Acb) complex, are a major cause of hospital acquired infection. In the burn wound center of the Queen Astrid military hospital in Brussels, 48 patients were colonized or infected with Acb complex over a 52-month period. We report the molecular epidemiology of these organisms, their clinical impact and infection control measures taken. A representative set of 157 Acb complex isolates was analyzed using repetitive sequence-based PCR (rep-PCR) (DiversiLab) and a multiplex PCR targeting OXA-51-like and OXA-23-like genes. We identified 31 rep-PCR genotypes (strains). Representatives of each rep-type were identified to species by rpoB sequence analysis: 13 types to A. baumannii, 10 to A. pittii, and 3 to A. nosocomialis. It was assumed that isolates that belonged to the same rep-type also belonged to the same species. Thus, 83.4% of all isolates were identified to A. baumannii, 9.6% to A. pittii and 4.5% to A. nosocomialis. We observed 12 extensively drug resistant Acb strains (10 A. baumannii and 2 A. nosocomialis), all carbapenem-non-susceptible/colistin-susceptible and imported into the burn wound center through patients injured in North Africa. The two most prevalent rep-types 12 and 13 harbored an OXA-23-like gene. Multilocus sequence typing allocated them to clonal complex 1 corresponding to EU (international) clone I. Both strains caused consecutive outbreaks, interspersed with periods of apparent eradication. Patients infected with carbapenem resistant A. baumannii were successfully treated with colistin/rifampicin. Extensive infection control measures were required to eradicate the organisms. Acinetobacter infection and colonization was not associated with increased attributable mortality. PMID:27223476
Seth M. Daly
Full Text Available In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains. Therefore, the ability to inhibit MCR-1 and restore polymyxin sensitivity would be an important scientific advancement. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs are antisense molecules that were designed to target mRNA, preventing translation. Peptide conjugation enhances cellular entry, but they are positively charged, so we tested our lead antibacterial PPMOs by targeting an essential Escherichia coli gene, acpP, and demonstrated that they were still effective in mcr-1-positive E. coli strains. We then designed and synthesized two PPMOs targeted to mcr-1 mRNA. Five clinical mcr-1-positive E. coli strains were resensitized to polymyxins by MCR-1 inhibition, reducing MICs 2- to 16-fold. Finally, therapeutic dosing of BALB/c mice with MCR-1 PPMO combined with colistin in a sepsis model reduced morbidity and bacterial burden in the spleen at 24 h and offered a survival advantage out to 5 days. This is the first example of a way to modulate colistin resistance with an antisense approach and may be a viable strategy to combat this globally emerging antibiotic resistance threat.
Régis Fernando Pastorelo Meurer
Full Text Available This work was carried out to evaluate the use of Bacillus subtilis probiotic C-3102 (10(10cfu/g in diets with or without growth promoters on the performance of broilers in the period from 1 to 42 days of age. It was used 1,200 Cobb line broilers, distributed in a complete randomized block with five diets: negative controller (without promoters; Bacillus subtilis (30 g/t ration; Bacillus subtilis (50 g/t ration; Bacillus subtilis (30 g/t ration + colistin (10 ppm; avilamycin (10 ppm + colistin (10 ppm. Each diet was evaluated in 10 repetitions with 24 birds. From 21 to 42 days of age, feed intake, weight gain and feed conversion were evaluated, and at 42 days of age, productive efficiency index was evaluated. At the end of the experimental period, it was observed an increase in the consumption of diet with the lowest dose of Bacillus subtilis (30 g in relation to that one with Bacillus subtillis (30 g + colistin (10 ppm. The values of weight gain obtained with the diet with the lowest dose of Bacillus subtillis (30 g and with avilamycin (10 ppm + colistine (10 ppm were higher than those of the birds fed control diet (without promoters. For feed conversion, the best results were obtained by supplying diets containing 50 g of Bacillus subtillis, diet with 30 g of Bacillus subtillis + 10 ppm of colistin; and diet with 10 ppm of avilamycin + 10 ppm colistin. For the analysis of productive efficiency index, the best results were obtained with diets containing additives (probiotics and/or antibiotics in comparison to the control diet. Bacillus subtillis C-3102 probiotic, at concentration 10(10 cfu/g, is an efficient substitute of antibiotics.Este trabalho foi realizado para avaliar o uso do probiótico Bacillus subtilis C-3102 (10(10 ufc/g em dietas contendo ou não promotores de crescimento sobre o desempenho de frangos de corte no período de 1 a 42 dias de idade. Foram utilizados 1.200 frangos de corte da linhagem Cobb, distribuídos em delineamento
Maynou, G; Bach, A; Terré, M
The use of milk containing antimicrobial residues in calf feeding programs has been shown to select for resistant fecal Escherichia coli in dairy calves. However, information is scarce about the effects of feeding calves waste milk (WM) on the prevalence of multidrug-resistant bacteria. The objective of this study was to determine the antimicrobial resistance patterns of fecal E. coli and nasal Pasteurella multocida isolates from calves fed either milk replacer (MR) or WM in 8 commercial dairy farms (4 farms per feeding program). Fecal and nasal swabs were collected from 20 ± 5 dairy calves at 42 ± 3.2 d of age, and from 10 of these at approximately 1 yr of age in each study farm to isolate the targeted bacteria. Furthermore, resistance of E. coli isolates from calf-environment and from 5 calves at birth and their dams was also evaluated in each study farm. Resistances were tested against the following antimicrobial agents: amoxicillin-clavulanic acid, ceftiofur, colistin, doxycycline (DO), enrofloxacin (ENR), erythromycin, florfenicol, imipenem, and streptomycin. A greater number of fecal E. coli resistant to ENR, florfenicol, and streptomycin and more multidrug-resistant E. coli phenotypes were isolated in feces of calves fed WM than in those fed MR. However, the prevalence of fecal-resistant E. coli was also influenced by calf age, as it increased from birth to 6 wk of age for ENR and DO and decreased from 6 wk to 1 yr of age for DO regardless of the feeding program. From nasal samples, an increase in the prevalence of colistin-resistant P. multocida was observed in calves fed WM compared with those fed MR. The resistance patterns of E. coli isolates from calves and their dams tended to differ, whereas similar resistance profiles among E. coli isolates from farm environment and calves were observed. The findings of this study suggest that feeding calves WM fosters the presence of resistant bacteria in the lower gut and respiratory tracts of dairy calves
Maria Virginia Villegas
Full Text Available Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE and non-CPE bloodstream infection (BSI from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy.Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela. Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information.A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001. The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255. Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001; however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002 and critical illness (aOR 6.5; 95% CI 3.1-13.7; p < 0.001 were independently
Evaluación microbiológica y epidemiológica de los clones de Acinetobacter baumannii resistentes a los carbapenemes aislados en la unidad de cuidados intensivos de un Hospital Universitario de la ciudad de Buenos Aires Microbiological and epidemiological evaluation of carbapenem-resistant Acinetobacter baumannii clones isolated at an intensive care unit of a University Hospital in Buenos Aires city
C. H. Rodriguez
survive on inert materials for more than 5 days, whereas adhesion to catheters was observed in isolates belonging to clones I and III, especially in those related to bacteremia. Clone III isolates showed colistin, gentamicin and levofloxacin susceptibility, whereas clone I isolates and most from clone IV were only susceptible to colistin and tetracyclines.
Lăzureanu, Voichița; Poroșnicu, Mirela; Gândac, Ciprian; Moisil, Teodora; Bădițoiu, Luminița; Laza, Ruxandra; Musta, Virgil; Crișan, Alexandru; Marinescu, Adelina-Raluca
Acinetobacter baumannii is one of the main causes of morbidity and mortality in critical condition patients. The pathogen's ability to survive under a wide range of environment conditions and to persist for long periods of time on areas represents a frequent cause of endemic infection hotbeds especially in the Intensive Care Unit. The objectives of the study are: determining the 5-year incidence of A. baumannii infection in patients admitted in the ICU which needed mechanical ventilation; the analysis of these cases regarding pathological antecedents; processing the data regarding these cases; gradual analysis of the susceptibility/resistance of isolated A. baumannii strains; observing the emergence of A. baumannii infection in patients transferred into the ICU. We have performed an observational retrospective study regarding the incidence of Acinetobacter baumannii infections in the Intensive Care Unit of the Hospital of Infectious Diseases and Pneumophtisiology "Victor Babes" Timisoara, Clinic II Infectious Diseases, during June 2011 - June 2015. We have identified a high prevalence of Acinetobacter baumannii infection, with an average period of 6 days. Bronchial suction was the most common pathological product in the study (90 % of the cases). Resistance to antimicrobials has been determined: the lowest resistance was recorded for ampicillin + sulbactam (81.1 %), and the highest resistance rate was recorded for ceftazidime and imipenem (94.6 % each). When comparing resistance to third generation cephalosporins, the difference was not statistically significant (94.6 % for ceftazidime vs. 86.5 % for cefoperazone, p = 0.117). Within the present study we were able to observe a significantly high resistance of the germ to carbapenems, with a good sensitivity to aminoglycosides, and to colistin. Only one strain of Acinetobacter baumannii was resistant to all classes of tested antibiotics. Generally, carbapenems represented the elective treatment in
Mahdian, Somayeh; Sadeghifard, Nourkhoda; Pakzad, Iraj; Ghanbari, Fatemeh; Soroush, Setareh; Azimi, Lila; Rastegar-Lari, Abdolaziz; Giannouli, Maria; Taherikalani, Morovat
The aim of this study was to analyze antimicrobial resistance patterns and their encoding genes and genotypic diversity of Acinetobacter baumannii isolated from burn patients in Tehran, Iran. The presence of extended-spectrum beta-lactamase- and blaOXA-encoding genes among 37 multidrug resistant (MDR) A. baumannii strains isolated from patients hospitalized in a teaching hospital in Tehran was evaluated. Susceptibility to 7 antibiotics was tested by disk agar diffusion and to polymyxin B and colistin was tested by E-test, according to CLSI guidelines. All isolates were then analyzed by PCR for the presence of blaIMP, blaVIM, blaSIMblaOXA-23, blaOXA-24, and blaOXA-58-like carbapenemase genes, and blaOXA-51-like, blaTEM, blaSHV, blaPER, blaVEB, and blaGIM genes. Genotyping of A. baumannii strains was performed by repetitive sequence-based (REP)-PCR and cluster analysis of REP-PCR profiles. A. baumannii isolates were assigned to international clones by multiplex PCR sequence group analysis. Twenty-five A. baumannii isolates were classified as MDR, and 12 were classified as extensively drug resistant. All isolates were susceptible to colistin and polymyxin B. Eighty-one percent of the isolates was resistant to imipenem or meropenem and harbored at least one or both of the blaOXA-23-like or blaOXA-24-like carbapenemase genes. Co-existence of different resistance genes was found among carbapenem-resistant isolates. Multiplex PCR sequence group analysis most commonly assigned A. baumannii isolates to international clones I (18/37; 48.6%) and II (18/37; 48.6%). An alarming increase in resistance to carbapenems and the spread of blaOXA-23-like and/or blaOXA-24-like carbapenemase genes was observed among A. baumannii strains belonging to clonal lineages I and II, isolated from burn patients in Tehran. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Rimoldi, Sara Giordana; Gentile, Bernardina; Pagani, Cristina; Di Gregorio, Annamaria; Anselmo, Anna; Palozzi, Anna Maria; Fortunato, Antonella; Pittiglio, Valentina; Ridolfo, Anna Lisa; Gismondo, Maria Rita; Rizzardini, Giuliano; Lista, Florigio
The emergence of carbapenem-resistant Klebsiella pneumoniae strains is threatening antimicrobial treatment. Sixty-eight carbapenemase-producing K. pneumoniae strains isolated at Luigi Sacco University Hospital-ASST Fatebenefratelli Sacco (Milan, Italy) between 2012 and 2014 were characterised microbiologically and molecularly. They were tested for drug susceptibility and carbapenemase phenotypes, investigated by means of repetitive extra-genic palindromic polymerase chain reaction (REP-PCR), and fully sequenced by means of next-generation sequencing for the in silico analysis of multi-locus sequence typing (MLST), their resistome, virulome and plasmid content, and their core single nucleotide polymorphism (SNP) genotypes. All of the samples were resistant to carbapenems, other β-lactams and ciprofloxacin; many were resistant to aminoglycosides and tigecycline; and seven were resistant to colistin. Resistome analysis revealed the presence of blaKPC genes and, less frequently blaSHV, blaTEM, blaCTX-M and blaOXA, which are related to resistance to carbapenem and other β-lactams. Other genes conferring resistance to aminoglycoside, fluoroquinolone, phenicol, sulphonamide, tetracycline, trimethoprim and macrolide-lincosamide-streptogramin were also detected. Genes related to AcrAB-TolC efflux pump-dependent and pump-independent tigecycline resistance mechanisms were investigated, but it was not possible to clearly correlate the genomic features with tigecycline resistance because of the presence of a common mutation in susceptible, intermediate and resistant strains. Concerning colistin resistance, the mgrB gene was disrupted by an IS5-like element, and the mobile mcr-1 and mcr-2 genes were not detected in two cases. The virulome profile revealed type-3 fimbriae and iron uptake system genes, which are important during the colonisation stage in the mammalian host environment. The in silico detected plasmid replicons were classified as IncFIB(pQil), IncFIB(K), Col
Castanheira, Mariana; Mendes, Rodrigo E; Sader, Helio S
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 Enterobacteriaceae isolates carrying bla KPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC 50/90 , 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC 50/90 , 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents. Only 80.5% and 59.0% of isolates were susceptible to colistin and amikacin, respectively. All three isolates (0.7%) displaying resistance to ceftazidime-avibactam ( K. pneumoniae ; MICs, ≥16 μg/ml) were evaluated using whole-genome sequencing analysis and relative quantification of expression levels of porins and efflux pump. Two isolates carried metallo-β-lactamase genes, bla NDM-1 or bla VIM-4 , among other β-lactam resistance mechanisms, and one displayed a premature stop codon in ompK35 and decreased expression of ompK36 Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carrying bla KPC-3 ( n = 221) and bla KPC-2 ( n = 145), respectively. Isolates carrying bla KPC were more commonly recovered from pneumonia ( n = 155), urinary tract ( n = 93), and skin/soft tissue ( n = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites. K. pneumoniae (83.3% of the collection) susceptibility rates were 99.2% for ceftazidime-avibactam, 98.9% for tigecycline, and 80.1% for colistin. Ceftazidime-avibactam susceptibility did not vary substantially when comparing isolates from intensive care unit (ICU) patients to those from non-ICU patients. Ceftazidime-avibactam was active against this large collection of isolates carrying bla KPC and represents a valuable addition to the armamentarium currently available for the
Ström, G; Boqvist, S; Albihn, A; Fernström, L-L; Andersson Djurfeldt, A; Sokerya, S; Sothyra, T; Magnusson, U
Administration of antimicrobials to food-producing animals is regarded as a major contributor to the overall emergence of resistance in bacteria worldwide. However, few data are available on global antimicrobial use and resistance (AMR) in livestock, especially from low- and middle-income countries. We conducted a structured survey of 91 small-scale pig farms in the urban and peri-urban areas of Phnom Penh, Cambodia, to assess the farmers' knowledge, attitudes and practices related to antimicrobial use in their pig production. Commensal Escherichia coli was isolated from three healthy pigs from each farm ( n = 261) and susceptibility testing was performed against 14 antimicrobials, using broth microdilution. Univariable logistic regression and generalized linear mixed models were used to investigate potential associations between farm characteristics, management factors and resistance to different types of antimicrobials. We found a widespread and arbitrary use of antimicrobials, often based on the farmer's own judgment. Around 66% of the farmers reported frequently self-adjusting treatment duration and dosage, and 45% had not heard about the term 'antimicrobial resistance'. The antimicrobials most commonly mentioned or kept by the farmers were amoxicillin, tylosin, gentamicin and colistin. Around 37% used a feed concentrate that contained antimicrobials, while antimicrobials for humans were used as a last-line treatment by 10% of the farmers. Commensal E. coli exhibited high prevalence of resistance to several antimicrobials considered to be of critical importance for human medicine, including ampicillin, ciprofloxacin and colistin, and multidrug-resistance was found in 79% of the samples. Higher prevalence of resistance was observed on farms that administered prophylactic antimicrobials and on farms that treated the entire group or herd in the event of disease. The widespread and arbitrary use of antimicrobials in pig farming in Cambodia is highly worrisome
Full Text Available Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014–2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205 followed by 25% of Klebsiella pneumoniae (n = 676 and 11% of Pseudomonas aeruginosa (n = 308. Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL-positive isolates were ranged from 66%–77% in E. coli to 61%–72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that
Marzouk, M; Ferjani, A; Haj Ali, M; Boukadida, J
We present recent data on the bacteriological profile and antibiotic susceptibility of uropathogenic bacteria isolated in children and newborns in our region over the past 2 years. A retrospective study on the positive urine cultures from pediatric and neonatal populations during 2012-2013. Bacteria were identified using conventional methods. Susceptibility testing was performed and interpreted as recommended by the committee of the susceptibility of the French Society of Microbiology (CA-SFM). We collected 1879 non-redundant bacteria with more than 73% Escherichia coli. Children and infants (mean age, 32 months [range, 1 month to 14 years]) accounted for 84% of the bacteria collected and newborns (mean age, 12 days [range, 1 day to 1 month]) 16%. A female predominance was observed in the pediatric population (M:F sex ratio, 3.2), whereas for the neonatal population, the proportions were almost identical in both sexes (M:F sex ratio, 1.1). Most of the positive urine cultures (n=1234) were from the community. Hospitalized patients (n=636) were divided into pediatric (60%) and neonatal units (40%). Five bacterial genera dominated the bacteriological profile: E. coli, Klebsiella sp., Proteus sp., Enterobacter sp., and Enterococcus. The susceptibility of the main BUP antibiotics used for treatment of frequent UTI showed the effectiveness of furadoine, imipenem, fosfomycin, and colistin. Amoxicillin kept constant activity against Enterococcus and Streptococcus agalactiae. The rates of resistance of Enterobacteriaceae to beta-lactam antibiotics were high, especially in the neonatal population. The production of extended-spectrum beta-lactamase (ESBL) was noted in 12.8% of pediatric Enterobacteria vs. 22.6% of the neonatal strains. For community Enterobacteriaceae, the activity of beta-lactam antibiotics was limited with 11.2% resistance to third-generation cephalosporins (C3G), including 8.6% ESBL production. The impact of widespread use of beta-lactam antibiotics in
Full Text Available Objective: Our investigation is about the determination of the antibacterial efficiency of 22 medicinal plants on the four most frequent bacteria in urinary infections. These infections are responsible for more than 15% of urinary stones formation. Methods: We have initiated an extraction liquid/solid. In this respect, we have used water extractions according to the standard methods utilized by the local population, i.e: (i the d écoction, (ii the infusion, (iii the mac ération and (iiii the percolation. The microorganisms used are Staphylooccus aureus, Escherichia coli, Proteus mirabilis and Pseudomonas aeruginosa. The strains were isolated from patients having urinary infections. The antibiotic disks Kanamicin, Colistin, Amoxicillin, Gentamicin, Ampicillin were applied to the reference bacteria at concentrations of 30 毺 g, 50毺 g, 25毺 g, 10毺 g et 10毺 g respectively. Results: These studies showed that decoction (d had the higher effect with 43.3 % followed by percolation (p (28.3% and maceration (m (16.7%. Infusion (i had a limited effect (11.7%. Escherichia coli (E.coli, Proteus mirabilis, Staphylococcus aureus showed an average sensitivity of 28% in each case. However, Pseudomonas aeruginosa, a highly pathogenic and resistant bacteria showed up to 17.5% of sensitivity. 16.3% of the plant extracts showed a high antimicrobial activity. Pseudomonas aeruginosa was highly resistant to Kanamycin, Amoxicillin and Ampicillin and at a lower extent to Colistin and Gentamicin. However, it was sensitive to some plant extracts such as Allium sativum, Artemesia compestris(p,m, Citrus aurantium(p, Cotula cinerea(p, Lavandula officinalis (d , Globularia alypum (d , Juniperus phoeniceae (m , Olea europaea (p, Pistacia lentiscus (m , Trachyspermum ammi (m, Zygophyllum album (p and Zingiber officinalis (d. Conclusion: The present work shows that most of the studied plants are potentially a good source of antimicrobial agents and it proves the
Full Text Available AbstrakAcinetobacter baumannii merupakan spesies Acinetobacter spp. tersering diisolasi darimanusia, dan lebih sering dijumpai pada infeksi nosokomial dibandingkan dengan infeksi dikomunitas. Eksistensi bakteri ini di lingkungan terkait dengan keragaman reservoir, kemampuanmemperoleh gen pembawa sifat resisten antimikroba, dan sifat resisten terhadap pengeringan.Infeksi disebabkan strain A.baumannii yang resisten terhadap banyak antibiotik tidak mudahdikendalikan dan menjadi permasalahan di berbagai negara. Penelitian ini bertujuan untukmengetahui prevalensi A.baumannii dari spesimen klinis di instalasi mikrobiologi klinik RSUPHaji Adam Malik serta pola kepekaannya terhadap berbagai antibiotik. Identifikasi dan ujikepekaan menggunakan mesin otomatis Vitek 2 dengan Advanced Expert System (AES.Penelitian ini menemukan 644/3693 (17,44% isolat A.baumannii dari berbagai spesimen klinis.A.baumannii paling banyak diisolasi dari spesimen dahak. Penelitian ini menemukan 147/644(23% bahwa isolat carbapenem-resistent A.baumannii (imipenem dan meropenem. Sebagianbesar isolat sensitif terhadap colistin, amikacin dan tigecycline. Prevalensi A.baumanni yangditemukan pada penelitian ini adalah rendah namun resistensinya tinggi terhadap antibiotikterutama golongan penicillin, cephalosporin dan fluoroquinolon.AbstractAcinetobacter baumannii is the most frequent species of Acinetobacter spp. isolated fromhumans and more common in nosocomial infection than it is in community acquired infection.A.baumannii existence in environment is associated with the diversity of its reservoirs, itscapacity to accumulate genes of antimicrobial resistence, and its resistence to desiccation.Infection of Multidrug resistent (MDR strain of A.baumannii is not easy to manage and it hasbecome a problem in many countries. The aim of this retrospective study was to investigatethe prevalence of A.baumannii from routine clinical specimens sent to clinical microbiologylaboratory RSUP HAM
Brand, P; Gobeli, S; Perreten, V
A total of 131 porcine E. coli were isolated in 2014 and 2015 from the gut of 115 pigs raised in Switzerland and suffering from diarrhea. The isolates were tested for antibiotic resistance, serotypes, virulence factors and genetic diversity. Serotypes were assigned by agglutination tests and virulence genes were identified by polymerase chain reaction (PCR). Antibiotic resistance profile was determined by the measurement of the MIC of 14 antibiotics and by the detection of the corresponding genes using microarray and PCR approaches. Genetic diversity was determined by repetitive palindromic PCR (rep- PCR) revealing a heterogenous population. Half of the E. coli isolates possessing virulence factors could not be assigned to any of the 19 serotypes tested, but contained toxins and adhesins similarly to the sero-typable E. coli isolates. The most prevalent E. coli serotypes found were K88ac (18%), O139:K82 (6%), O141:K85ac (5%), O108:K`V189` (5%), O119:K`V113` (3%) and O157:K`V17` (2%). The combination of toxins EAST-1, STb and LT-I and adhesin F4 characterizing ETEC was the most frequent. The shigatoxin Stx2e (STEC) and intimin Eae (EPEC) were also detected, but less frequently. Seventy percent of the isolates were resistant to at least one antibiotic and 29% were resistant to more than 3 antibiotics. Isolates exhibited resistance to tetracycline (50%) associated to resistance genes tet(A), tet(B) and tet(C), sulfamethoxazole (49%) [sul1, sul2 and sul3], trimethoprim (34%) [dfr], nalidixic acid (29%), ampicillin (26%) [blaTEM-1], gentamicin (17%) [aac(3) -IIc, aac(3) -IVa and aac(3) -VIa], chloramphenicol (17%) [catAI and catAIII], and ciprofloxacin (8%) [mutations in GyrA (S83L) and ParC (S80I)]. All isolates were susceptible to 3rd generation cephalosporins, carbapenems, colistin and tigecycline. Pathogenic E. coli isolates from pigs in Switzerland could frequently not be assigned to a known serotype even if they contained diarrhea-causing virulence factors. They
Villegas, Maria Virginia; Pallares, Christian J.; Hernández-Gómez, Cristhian; Correa, Adriana; Álvarez, Carlos; Rosso, Fernando; Matta, Lorena; Luna, Carlos; Zurita, Jeannete; Mejía-Villatoro, Carlos; Rodríguez-Noriega, Eduardo; Seas, Carlos; Cortesía, Manuel; Guzmán-Suárez, Alfonso; Guzmán-Blanco, Manuel
Introduction Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Methods Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. Results A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7–9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1–13.7; p < 0
Full Text Available Metallo-beta-lactamase (MBL-producing Pseudomonas aeruginosa strains have been reported to be an important cause of nosocomial infections. There is not enough information from India regarding their prevalence in diabetic and cancer patients. The present study was undertaken over a period of one year from January to December 2006 to study the incidence of MBL P. aeruginosa and the clinical outcome in diabetes and cancer patients admitted to S.L. Raheja Hospital, Mumbai. Two hundred and thirty isolates of P. aeruginosa were obtained from different samples of patients. These isolates were subjected to susceptibility testing to anti-pseudomonal drugs as per CLSI guidelines. They were further screened for the production of MBL by disc potentiation testing using EDTA-impregnated imipenem and meropenem discs. Of the 230 isolates of P. aeruginosa, 60 (26% isolates were found resistant to carbapenems (both imipenem and meropenem and 33 (14.3% were found to be MBL producers. Of the 33 MBL-producing isolates, 24 (72.7% were diabetic patients, six (18.1% were cancer patients and three (9% patients had both diabetes and cancer. Five (15.1% patients responded to the combination therapy of colistin, piperacillin with tazobactam and amikacin, while 28 (84.8% patients responded to the combination therapy of amikacin, piperacillin with tazobactam and gatifloxacin. Thus, the rapid dissemination of MBL producers is worrisome and necessitates the implementation of not just surveillance studies but also proper and judicious selection of antibiotics, especially carbapenems.
Full Text Available Multidrug-resistant Acinetobacter baumannii (MDRAB is an increasing problem worldwide. Prevalence of carbapenem resistance in Acinetobacter spp. due to acquired carbapenemase genes is not known in Finland. The purpose of this study was to examine prevalence and clonal spread of multiresistant A. baumannii group species, and their carbapenemase genes. A total of 55 Acinetobacter isolates were evaluated with repetitive PCR (DiversiLab to analyse clonality of isolates, in conjunction with antimicrobial susceptibility profile for ampicillin/sulbactam, colistin, imipenem, meropenem, rifampicin and tigecycline. In addition, a new real-time PCR assay, detecting most clinically important carbapenemase genes just in two multiplex reactions, was developed. The assay detects genes for KPC, VIM, IMP, GES-1/-10, OXA-48, NDM, GIM-1, SPM-1, IMI/NMC-A, SME, CMY-10, SFC-1, SIM-1, OXA-23-like, OXA-24/40-like, OXA-58 and ISAbaI-OXA-51-like junction, and allows confident detection of isolates harbouring acquired carbapenemase genes. There was a time-dependent, clonal spread of multiresistant A. baumannii strongly correlating with carbapenamase gene profile, at least in this geographically restricted study material. The new carbapenemase screening assay was able to detect all the genes correctly suggesting it might be suitable for epidemiologic screening purposes in clinical laboratories.
Lesho, Emil P; Waterman, Paige E; Chukwuma, Uzo; McAuliffe, Kathryn; Neumann, Charlotte; Julius, Michael D; Crouch, Helen; Chandrasekera, Ruvani; English, Judith F; Clifford, Robert J; Kester, Kent E
Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Designation of pathogenic resistant bacteria in the Sparusaurata sea collected in Tunisia coastlines: Correlation with high performance liquid chromatography-tandem mass spectrometry analysis of antibiotics.
Zouiten, Amina; Mehri, Ines; Beltifa, Asma; Ghorbel, Asma; Sire, Olivier; Van Loco, Joris; Abdenaceur, Hassen; Reyns, Tim; Ben Mansour, Hedi
Vibrio is characterized by a large number of species and some of them are human pathogens causing gastro intestinal and wound infections through the ingestion or manipulation of contaminated fishes including Vibrio parahaemolyticus and Vibrio alginolyticus. In this study, we reported the phenotypic and molecular characterization of Vibrio parahaemolyticus and Vibrio alginolyticus strains isolated from wild and farm sea bream (Sparus aurata L.) along the Tunisian coast from December 2015 to April 2016. Therefore, the antibiograms indicate a difference between farmed and wild fish. Resistance against amoxicillin antibiotic appears for the bacteria isolated from wild fish, while those from aquaculture farming presented sensitivity to amoxicillin and resistance to antibiotics colistin and fusidic acid. The chloramphenicol antibiotic exhibited a high sensitivity in all isolated bacteria. In fact, traces of amoxicillin in the organs of the fish from Hergla farm were detected by UPLC-MS/MS analysis during December 2016 to April 2016. In addition, antibiotics were detected in January 2014 with high concentration of norfloxacin 2262 ng/g in fish from Hergla coast. The results obtained in this work indicated that the use and presence of antibiotics in water impacts on the occurrence of resistant bacteria and the detection of antibiotic in fish. Copyright © 2017. Published by Elsevier Ltd.
Sierra, Josep M; Fusté, Ester; Rabanal, Francesc; Vinuesa, Teresa; Viñas, Miguel
The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.
Full Text Available Following a worldwide trend, infections caused by MDR OXA-type (Ambler class D carbapenemase-producing Acinetobacter baumannii are currently regarded as a clinical and epidemiological emergency in Brazil. OXA-producing A. baumannii strains have been identified in the states of Alagoas, Amazonas, Bahia, Distrito Federal, Espírito Santo, Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Paraná, Pernambuco, Rio de Janeiro, Rio Grande do Norte, Rio Grande do Sul, Santa Catarina and São Paulo. In some settings, the presence of OXA-23- and/or OXA-143 -producing A. baumannii (so far restricted to Brazil has been endemic and A. baumannii strains carrying blaOXA-23 genes have been detected in hospital wastewater effluents, hence a potential risk to the community and the environment. Although molecular typing by multilocus sequence typing (MLST - Bartual scheme, University of Oxford, http://pubmlst.org/abaumannii/ has revealed the international spread of a clonal complex (CC denominated CC92, in Brazil most OXA-23-producing A. baumannii belong to CC113, CC109 or CC104 clonal complexes. Finally, from a clinical point of view, the main problem of A. baumannii infections is the limited use of antibacterial agents with in vitro activity, often restricted to ampicillin/sulbactam, polymyxin B and/or colistin (polymyxin E.
Lin, Ming-Feng; Lan, Chung-Yu
Acinetobacter baumannii (A. baumannii) is undoubtedly one of the most successful pathogens in the modern healthcare system. With invasive procedures, antibiotic use and immunocompromised hosts increasing in recent years, A. baumannii has become endemic in hospitals due to its versatile genetic machinery, which allows it to quickly evolve resistance factors, and to its remarkable ability to tolerate harsh environments. Infections and outbreaks caused by multidrug-resistant A. baumannii (MDRAB) are prevalent and have been reported worldwide over the past twenty or more years. To address this problem effectively, knowledge of species identification, typing methods, clinical manifestations, risk factors, and virulence factors is essential. The global epidemiology of MDRAB is monitored by persistent surveillance programs. Because few effective antibiotics are available, clinicians often face serious challenges when treating patients with MDRAB. Therefore, a deep understanding of the resistance mechanisms used by MDRAB can shed light on two possible strategies to combat the dissemination of antimicrobial resistance: stringent infection control and antibiotic treatments, of which colistin-based combination therapy is the mainstream strategy. However, due to the current unsatisfying therapeutic outcomes, there is a great need to develop and evaluate the efficacy of new antibiotics and to understand the role of other potential alternatives, such as antimicrobial peptides, in the treatment of MDRAB infections. PMID:25516853
Shrestha, Shovita; Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Ohara, Hiroshi; Shimada, Kayo; Satou, Kazuhito; Teruya, Kuniko; Nakano, Kazuma; Shiroma, Akino; Sherchand, Jeevan Bdr; Rijal, Basista Psd; Hirano, Takashi; Kirikae, Teruo; Pokhrel, Bharat Mani
The emergence of multidrug-resistant (MDR) Acinetobacter baumannii has become a serious medical problem worldwide. To clarify the genetic and epidemiological properties of MDR A. baumannii strains isolated from a medical setting in Nepal, 246 Acinetobacter spp. isolates obtained from different patients were screened for MDR A. baumannii by antimicrobial disk susceptibility testing. Whole genomes of the MDR A. baumannii isolates were sequenced by MiSeq™ (Illumina), and the complete genome of one isolate (IOMTU433) was sequenced by PacBio RS II. Phylogenetic trees were constructed from single nucleotide polymorphism concatemers. Multilocus sequence types were deduced and drug resistance genes were identified. Of the 246 Acinetobacter spp. isolates, 122 (49.6%) were MDR A. baumannii, with the majority being resistant to aminoglycosides, carbapenems and fluoroquinolones but not to colistin and tigecycline. These isolates harboured the 16S rRNA methylase gene armA as well as bla(NDM-1), bla(OXA-23) or bla(OXA-58). MDR A. baumannii isolates belonging to clonal complex 1 (CC1) and CC2 as well as a novel clonal complex (CC149) have spread throughout a medical setting in Nepal. The MDR isolates harboured genes encoding carbapenemases (OXA and NDM-1) and a 16S rRNA methylase (ArmA). Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
El-Mahdy, Taghrid S; Al-Agamy, Mohamed H; Al-Qahtani, Ahmed A; Shibl, Atef M
Acinetobacter baumannii is currently considered as one of the most common successful pathogens in the healthcare system due to its ability to quickly develop resistance. Ten carbapenem-resistant A. calcoaceticus-baumannii complex were isolated from the eastern region, Saudi Arabia in 2014. All isolates were resistant to ciprofloxacin, however, 8 of 10 isolates were tigecycline resistant. Susceptibility test was also carried out for three aminoglycosides, resistance to gentamicin was 80%, amikacin was 90%, and tobramycin was 50%. Colistin susceptibility was seen in all isolates. The 10 isolates harbored bla OXA-23-like and ISAba1 and 9 of them also carried bla ADC . Three isolates of 10 harbored bla NDM-1 coding for NDM metallo-β-lactamase (MBL) with coexistence of bla ADC together with either bla GES or bla TEM or both. Those three isolates exhibited negative Etest MBL screening test. Pulsed-field gel electrophoresis revealed the high clonal variability of the isolates, although two isolates were indistinguishable. The risk of dissemination of carbapenem resistance through presence of ISAba1 upstream of OXA-23-like in all isolates raises the concern about emergence of higher carbapenem prevalence rates in the future in our region. This study also demonstrated the importance of molecular surveillance to provide accurate and reliable data about the resistance rates of A. baumannii. Finally, the high incidence of NDM-1 among our isolates requires a routine surveillance to monitor the future prevalence of this enzyme in the region.
Doi, Yohei; Murray, Gerald L.; Peleg, Anton Y.
The first decade of the 20th century witnessed a surge in the incidence of infections due to several highly antimicrobial-resistant bacteria in hospitals worldwide. Acinetobacter baumannii is one such organism that turned from an occasional respiratory pathogen into a major nosocomial pathogen. An increasing number of A. baumannii genome sequences have broadened our understanding of the genetic makeup of these bacteria and highlighted the extent of horizontal transfer of DNA. Animal models of disease combined with bacterial mutagenesis have provided some valuable insights into mechanisms of A. baumannii pathogenesis. Bacterial factors known to be important for disease include outer membrane porins, surface structures including capsule and lipopolysaccharide, enzymes such as phospholipase D, iron acquisition systems, and regulatory proteins. A. baumannii has a propensity to accumulate resistance to various groups of antimicrobial agents. In particular, carbapenem resistance has become commonplace, accounting for the majority of A. baumannii strains in many hospitals today. Carbapenem-resistant strains are often resistant to all other routinely tested agents. Treatment of carbapenem-resistant A. baumannii infection therefore involves the use of combinations of last resort agents such as colistin and tigecycline, but the efficacy and safety of these approaches are yet to be defined. Antimicrobial-resistant A. baumannii has high potential to spread among ill patients in intensive care units. Early recognition and timely implementation of appropriate infection control measures is crucial in preventing outbreaks. PMID:25643273
Heidary, Mohsen; Salimi Chirani, Alireza; Khoshnood, Saeed; Eslami, Gita; Atyabi, Seyyed Mohammad; Nazem, Habibollah; Fazilati, Mohammad; Hashemi, Ali; Soleimani, Saleh
Acinetobacter baumannii is a major opportunistic pathogen in healthcare settings worldwide. In Iran, there are only few reports on the prevalence of aminoglycoside resistance genes among A. baumannii isolates. The aim of this study was to investigate the existence of aminoglycoside-modifying enzyme (AME) genes from A. baumannii strains collected at a university teaching hospital in Iran. One hundred A. baumannii strains were collected between 2014 and 2015 from hospitalized patients at Loghman Hakim Hospital, Tehran, Iran. Antimicrobial susceptibility was determined by disk diffusion method according to the Clinical and Laboratory Standards Institute recommendations. The DNA was extracted using a kit obtained from Bioneer Co. (Korea) and was used as a template for polymerase chain reaction. The most active antimicrobial agent against these strains was colistin. The rate of extended-spectrum cephalosporin resistance was 97%. The aadA1, aadB, aac(6')-Ib, and aac(3)-IIa genes were found in 85%, 77%, 72%, and 68% of A. baumannii isolates, respectively. This study showed a high prevalence rate of AME genes in A. baumannii. This prevalence rate has explained that further aminoglycoside resistance genes may have role in the resistance of clinical isolates of A. baumannii. Therefore, control and treatment of serious infections caused by this opportunistic pathogen should be given more consideration.
Full Text Available Objective: In this study, we molecularly characterized 12 NDM-1 producing clinical Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae isolates that were part of a collection of non-carbapenem susceptible isolates obtained during a one-year period. These isolates were obtained from four local general hospitals in Singapore.Methods: Polymerase chain reaction (PCR assays and sequencing was used to determine the presence of β-lactamase encoding genes (bla including blaNDM-1 and plasmid-mediated quinolone and aminoglycoside resistance determinants. Conjugation experiments were performed to determine the transferability of blaNDM-1. Isolate relatedness was determined by multilocus sequence typing (MLST.Results: The isolates were completely resistant to the second- and third-generation cephalosporins tested as well as carbapenems. Susceptibility profiling of the isolates indicated that 100% retained susceptibility to tigecycline while 11/12 (91.7% were susceptible to colistin. The blaNDM-1 gene was encoded on plasmids that were easily transferable. None of the patients had a travel history to countries where NDM-1 has been reported. The isolates appear clonally unrelated with MLST, revealing a diversity of clonal types among the K. pneumoniae and E. coli isolates.Conclusion: The ease of NDM-1 plasmid transmissibility may help their dissemination among the Enterobacteriaceae. Although it appears that the isolates are clonally unrelated, epidemiological links cannot be fully excluded without further research.
Luczkiewicz, Aneta; Kotlarska, Ewa; Artichowicz, Wojciech; Tarasewicz, Katarzyna; Fudala-Ksiazek, Sylwia
In this study, species distribution and antimicrobial susceptibility of cultivated Pseudomonas spp. were studied in influent (INF), effluent (EFF), and marine outfall (MOut) of wastewater treatment plant (WWTP). The susceptibility was tested against 8 antimicrobial classes, active against Pseudomonas spp.: aminoglycosides, carbapenems, broad-spectrum cephalosporins from the 3rd and 4th generation, extended-spectrum penicillins, as well as their combination with the β-lactamase inhibitors, monobactams, fluoroquinolones, and polymyxins. Among identified species, resistance to all antimicrobials but colistin was shown by Pseudomonas putida, the predominant species in all sampling points. In other species, resistance was observed mainly against ceftazidime, ticarcillin, ticarcillin-clavulanate, and aztreonam, although some isolates of Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudoalcaligenes, and Pseudomonas protegens showed multidrug-resistance (MDR) phenotype. Among P. putida, resistance to β-lactams and to fluoroquinolones as well as multidrug resistance become more prevalent after wastewater treatment, but the resistance rate decreased in marine water samples. Obtained data, however, suggests that Pseudomonas spp. are equipped or are able to acquire a wide range of antibiotic resistance mechanisms, and thus should be monitored as possible source of resistance genes.
Full Text Available Acinetobacter species are aerobic Gram variable coccobacilli that are now emerging as an important nosocomial pathogen. Infections caused by them are difficult to control due to multidrug resistance. The purpose of this study was to detect virulence factors namely gelatinase production, biofilm formation and antibiotic susceptibility of Acinetobacter species. Two hundred fifty six clinical samples collected from Bangabandhu Sheikh Mujib medical University (BSMMU and from burn unit of Dhaka Medical College Hospital were included in the study. Gelatinase production was seen on Luria Bertani agar media containing gelatin (30 gm/l and biofilm formation was detected in microtiter plate assay. Out of 256 clinical samples, 52 (20.3% were Acinetobacter species. Out of 52 Acinetobacter isolates, none were gelatinase producer but 39 (75% were found biofilm producers. Acinetobacter isolates were 100% resistant to ceftazidime, cefotaxime cefuroxime and ceftriaxone. High level of resistance was also recorded for amoxicillin (98.1%, aztreonam (98.1%, gentamicin (90.4%, ciprofloxacin (73.1%, amikacin (57.6%, netilmicin (53.8% and imipenem (44.2%. Susceptibility to colistin was maximum (96.2%. The present study demonstrated a high propensity of biofilm formation by the clinical isolates of Acinetobacter species and most of the Acinetobacter were multidrug resistant. Ibrahim Med. Coll. J. 2012; 6(1: 27-30
Full Text Available Group B Streptococcus (GBS remains the leading cause of severe bacterial infections (sepsis, meningitis, pneumonia in neonates. We compared the detection of GBS from recto-vaginal swabs on blood agar and two chromogenic media and evaluated their antibiotic susceptibility. A total of 1351 swabs were taken from pregnant women at 35-37 weeks of gestation. Following enrichment in Todd Hewitt broth + nalidixic acid and colistin, the samples were plated on Columbia CNA agar (CNA, chromID Strepto B agar (STRB and Granada Agar (GRAN, respectively. GBS were found in 22.4% of recto-vaginal swabs from pregnant women. Sensitivity, specificity, positive and negative predictive values of GBS detection were 88%, 88%, 81% and 96% for CNA, 99%, 97%, 90% and 99% for STRB and 94%, 99%, 98% e 99% for GRAN; Cohen’s k index concordances for CNA, STREB and GRAN were 0.68, 0.92 and 0.96, respectively. All isolates were susceptible to penicillin, whereas resistances of erythromycin and clindamycin were 40% and 42%, respectively. To conclude, selective broth enrichment combined with chromogenic plates is recommended for GBS screening in pregnant women.
Zoghlami, Ayoub; Kanzari, Lamia; Boukadida, Jalel; Messadi, Amen Allah; Ghanem, Abdelraouef
Pseudomonas aeruginosa is a known opportunistic pathogen frequently causing serious infections in burned patients. To analyze the epidemiological profile of Pseudomonas aeruginosa isolated in a Tunisian burn unit. During a 3-year period (from 01 July 2008 to 30 June 2011), 544 non repetitive strains of P. aeruginosa were isolated from burn patients. Susceptibility to antibiotics was assessed according to CA-SFM guidelines. Serotypes were identified by slide agglutination test using P.aeruginosa O antisera (Biorad). Producing carbapenemase was analyzed for 202 imipenem resistant isolates by EDTA test. Susceptibility testing data were stored in a laboratory data base using whonet 5.3 software. The most frequent sites of isolation were cutaneous infections and blood cultures (83.4%). The percentages of resistant isolates were as follows: ceftazidime: 34%; imipenem: 37.1%, ciprofloxacin: 27.1% and amikacin: 29.6%. The most prevalent serotypes were: 011(51%), 06(17%), 03 (8%), 04(12%), 012(5%). Among the 202 imipenem resistant strains, 58% expressed a metallocarbapenemase. All theses strains were resistant to all tested antibiotics except colistin and belonged to the serotype O11. The dissemination of carbapenemases strains must be contained by implementation of timely identification, strict isolation methods and better hygienic procedures.
Purohit, Manju Raj; Chandran, Salesh; Shah, Harshada; Diwan, Vishal; Tamhankar, Ashok J.; Stålsby Lundborg, Cecilia
Antibiotic-resistant bacteria are an escalating grim menace to global public health. Our aim is to phenotype and genotype antibiotic-resistant commensal Escherichia coli (E. coli) from humans, animals, and water from the same community with a ‘one-health’ approach. The samples were collected from a village belonging to demographic surveillance site of Ruxmaniben Deepchand (R.D.) Gardi Medical College Ujjain, Central India. Commensal coliforms from stool samples from children aged 1–3 years and their environment (animals, drinking water from children's households, common source- and waste-water) were studied for antibiotic susceptibility and plasmid-encoded resistance genes. E. coli isolates from human (n = 127), animal (n = 21), waste- (n = 12), source- (n = 10), and household drinking water (n = 122) carried 70%, 29%, 41%, 30%, and 30% multi-drug resistance, respectively. Extended spectrum beta-lactamase (ESBL) producers were 57% in human and 23% in environmental isolates. Co-resistance was frequent in penicillin, cephalosporin, and quinolone. Antibiotic-resistance genes blaCTX-M-9 and qnrS were most frequent. Group D-type isolates with resistance genes were mainly from humans and wastewater. Colistin resistance, or the mcr-1 gene, was not detected. The frequency of resistance, co-resistance, and resistant genes are high and similar in coliforms from humans and their environment. This emphasizes the need to mitigate antibiotic resistance with a ‘one-health’ approach. PMID:28383517
Al Mokh, S.
Antibiotics are considered as pollutants when they are present in aquatic ecosystems, ultimate receptacles of anthropogenic substances. These compounds are studied as their persistence in the environment or their effects on natural organisms. Numerous efforts have been made worldwide to assess the environmental quality of different water resources for the survival of aquatic species, but also for human consumption and health risk related. Towards goal, the optimization of analytical techniques for these compounds in aquatic systems remains a necessity. Our objective is to develop extraction and detection methods for 12 molecules of aminoglycosides and colistin in sewage treatment plants and hospitals waters. The lack of analytical methods for analysis of these compounds and the deficiency of studies for their detection in water is the reason for their study. Solid Phase Extraction (SPE) in classic mode (offline) or online followed by Liquid Chromatography analysis coupled with Mass Spectrometry (LC/MS/MS) is the most method commonly used for this type of analysis. The parameters are optimized and validated to ensure the best conditions for the environmental analysis. This technique was applied to real samples of wastewater treatment plants in Bordeaux and Lebanon. (author)
Yoshimura, H; Takagi, M; Ishimura, M; Endoh, Y S
Sixteen antimicrobial agents were tested for their activity against 68 isolates of Actinobacillus pleuropneumoniae by determining the minimum inhibitory concentrations (MICs). Ceftiofur and the fluoroquinolones danofloxacin and enrofloxacin were the most active compounds, with a MIC for 90% of the isolates (MIC90) of (0.05 microg/ml. The MIC90 values of benzylpenicillin, amoxicillin and aspoxicillin were 0.78 units/ml, 0.39 microg/ml and colistin and tiamulin. Of these, spectinomycin was the least active, with a MIC50 of 25 microg/ml, followed by tiamulin, with a MIC50 of 6.25 microg/ml. Of the 68 isolates tested, 49 (72.0%) were of serotype 2; 14 (20.5%) were of serotype 1; 2 each (3.0%) were of serotypes 5 and 6; and one was of serotype 7. Of the isolates, 23 (33.8%) were resistant to one or more of the major antibiotics. Antibiotic resistance was found only infrequently among serotype 2, with 5 (10.2%) of 49 isolates being resistant to chloramphenicol and/or oxytetracycline, while it occurred in 18 (94.7%) of the 19 isolates of other serotypes.
Full Text Available Background: The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections such as meningitis, endocarditis, skin and soft tissue infections, urinary tract infection, conjunctivitis, burn wound infection and bacteremia. This organism has been shown resistance to different antimicrobial agents. The aim of this study was to determination antibiotic resistance profile of Acinetobacter strains isolated from hospitalized patients in Taleghani hospital (Ahvaz, Iran. Materials and Methods: This cross-sectional study was conducted on 43 Acinetobacter strains isolated from hospitalized patients. Clinical specimens were cultured on microbiological media. Subsequently, drug susceptibility test was performed using the disc diffusion method according to CLSI recommendations. Results: Acinetobacter strains were isolated from different specimens consisting biopsy 24 (55.8%, wound 13 (30/2% and blood 6 (14%. In antimicrobial susceptibility testing, colistin exhibited the greatest activity (60.5% against isolated strains. 33 (76/7% isolates demonstrated resistance to imipenem. Conclusion: In outbreak situations, surveillance cultures of patients involved in the outbreak or who are deemed at risk for colonization/infection with the outbreak organism are often parts of the planned intervention.
Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.
No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.
Wind, Carolien M; de Vries, Henry J C; van Dam, Alje P
In response to antimicrobial resistance of Neisseria gonorrhoeae to last-resort extended-spectrum cephalosporins, combination therapy of azithromycin+ceftriaxone is now recommended. Dual therapy can be effective to treat monoresistant strains as well as multidrug-resistant strains, preferably employing the effect of in vitro synergy. As reports on in vitro synergy of azithromycin+ceftriaxone in N. gonorrhoeae are conflicting, in this study an evaluation of this combination was performed using a cross-wise Etest method and agar dilution. Synergy was defined as a fractional inhibitory concentration index (FICI) of ≤0.5. To identify other dual treatment options for gonorrhoea, in vitro synergy was evaluated for 65 dual antimicrobial combinations using Etest. Azithromycin, cefixime, ceftriaxone, colistin, ertapenem, fosfomycin, gentamicin, minocycline, moxifloxacin, rifampicin, spectinomycin and tigecycline were screened for synergy in all possible combinations. No synergy or antagonism was found for any of the 65 combinations. The geometric mean FICI ranged from 0.82 to 2.00. The mean FICI of azithromycin+ceftriaxone was 1.18 (Etest) and 0.55 (agar dilution). The difference between both methods did not result in a difference in interpretation of synergy. Ceftriaxone-resistant strain F89 was tested in all combinations and no synergy was found for any of them. Most importantly, the ceftriaxone minimum inhibitory concentration of F89 was not decreased below the breakpoint with any concentration of azithromycin. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Full Text Available The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1, IncX3 plasmids harboring blaNDM-4 (n = 2 or blaNDM-7 (n = 1, IncFII plasmids harboring blaNDM-4 (n = 1 or blaNDM-5 (n = 3, and a multireplicon F plasmid harboring blaNDM-5 (n = 1. Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.
Hickman-Brenner, F W; Huntley-Carter, G P; Saitoh, Y; Steigerwalt, A G; Farmer, J J; Brenner, D J
The name Moellerella wisconsensis is proposed for a group of the family Enterobacteriaceae previously called enteric group 46. The species name, wisconsensis, was coined because six of the nine strains were isolated in Wisconsin. M. wisconsensis strains were negative for indole production, Voges-Proskauer, H2S production, urea, phenylalanine deaminase, lysine and ornithine decarboxylases, arginine dihydrolase, gas production from D-glucose, acid production from trehalose, and motility; the strains were positive for methyl red, citrate (Simmons), and acid production from lactose and raffinose and resistant to colistin. DNAs from five strains of M. wisconsensis were highly related (80 to 93% in reactions assayed on hydroxyapatite at 60 degrees C and 78 to 97% at 75 degrees C) to 32P-labeled DNA of the proposed type strain (CDC 2896-78, ATCC 35017). Labeled DNA from this type strain was only 2 to 32% related (at 60 degrees C) to DNA from 49 strains of named and unnamed species of Enterobacteriaceae. Eight of nine M. wisconsensis strains were isolated from human stool samples. Clinical information on one strain was available, and it was found to be associated with a case of diarrhea. On MacConkey agar, colonies of M. wisconsensis were bright red with precipitated bile around them and thus were indistinguishable from Escherichia coli colonies. Future studies should focus on the isolation of this new organism and its relationship to human disease.
Moxon, Christopher Alan; Paulus, Stéphane
Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Sevillano, Elena; Fernández, Elena; Bustamante, Zulema; Zabalaga, Silvia; Rosales, Ikerne; Umaran, Adelaida; Gallego, Lucía
Acinetobacter baumannii is an emerging multidrug-resistant pathogen and very little information is available regarding its imipenem resistance in Latin American countries such as Bolivia. This study investigated the antimicrobial resistance profile of 46 clinical strains from different hospitals in Cochabamba, Bolivia, from March 2008 to July 2009, and the presence of carbapenemases as a mechanism of resistance to imipenem. Isolates were obtained from 46 patients (one isolate per patient; 30 males,16 females) with an age range of 1 day to 84 years, and were collected from different sample types, the majority from respiratory tract infections (17) and wounds (13). Resistance to imipenem was detected in 15 isolates collected from different hospitals of the city. These isolates grouped into the same genotype, named A, and were resistant to all antibiotics tested including imipenem, with susceptibility only to colistin. Experiments to detect carbapenemases revealed the presence of the OXA-58 carbapenemase. Further analysis revealed the location of the bla(OXA-58) gene on a 40 kb plasmid. To our knowledge, this is the first report of carbapenem resistance in A. baumannii isolates from Bolivia that is conferred by the OXA-58 carbapenemase. The presence of this gene in a multidrug-resistant clone and its location within a plasmid is of great concern with regard to the spread of carbapenem-resistant A. baumannii in the hospital environment in Bolivia.
Full Text Available Hayat Ennaji1,2, Mohammed Timinouni2, My Mustapha Ennaji3, Mohammed Hassar1, Nozha Cohen11Laboratoire de Microbiologie et Hygiène des Aliments et de l’Environnement, Institut Pasteur du Maroc., Casablanca, Morocco; 2Laboratoire de Microbiologie et Biologie Moléculaire, Institut Pasteur du Maroc., Casablanca, Morocco; 3Laboratoire de Virologie et Hygiène and Microbiologie., Faculté des Sciences et Techniques - Mohammedia, Université Hassan II, Mohammedia, MoroccoAbstract: This study was carried out on 426 samples of raw meats collected from butcheries and supermarkets in Casablanca, Morocco. The samples were examined for the occurrence of Listeria species. Strains of Listeria monocytogenes were characterized by several biochemical tests and confirmed by polymerase chain reaction (PCR. β-hemolytic cultures and nonhemolytic isolates were tested for biochemical properties with the Listeria API test. Among the 43 Listeria species isolates; we identified 10 strains for L. monocytogenes (23.3%, 31 strains for L. innocua (72.1% and 2 strains for L. welshimeri (4.6%. Strains of L. monocytogenes were separated by multiplex PCR; two serogroups IIb and IVb were thus differentiated. Antibiotic susceptibility of L. monocytogenes to 21 antibiotics was determined by the disk diffusion method. All isolates were susceptible to a wide range of the tested antibiotics with the exception of nalidixic acid, colistine and cephalosporins second and third generation for which they were all resistant.Keywords: antibiotic susceptibility, Listeria monocytogenes, meat, PCR
Full Text Available Background: The emergence of antimicrobial-resistant bacteria with biofilm formation ability may be a major threat to public health and food safety and sanitation. Objectives: The aim of this study was to determine antibiotic resistance patterns and biofilm production characteristics of Salmonella typhimurium isolated from different species of birds. Materials and Methods: The antibiotic resistance patterns of 38 pre-identified isolates were screened by standard Kirby-Bauer disc-diffusion method performed on Mueller–Hinton agar to a panel of 17 antibiotics. The extent of biofilm formation was measured by Microtiter plate (MTP-based systems. Results: The highest antimicrobial resistance was detected against nalidixic acid (97%, followed by doxycycline (86%, colistin (84%, streptomycin (84% and tetracycline (84%. All isolates were sensitive to amikacin (100% and 97% and 95% of the isolates were sensitive to ceftazidime and ceftriaxone, respectively. Twenty one different antibiotic resistance patterns were observed among S. typhimurium isolates. According to the results of the microtitre plate biofilm assay, there was a wide variation in biofilm forming ability among S. typhimurium isolates. Most of the isolates (60.52% were not capable of producing biofilm, while 26.31%, 7.89%, and 5.26% isolates were weak, strong and moderate biofilm producers, respectively. Conclusions: It was concluded that nearly all S. typhimurium isolates revealed a high multiple antibiotic resistant with low biofilm forming capabilities which proposed low association between biofilm formation and antibiotic resistance of a major food important pathogen.
Full Text Available Tigecycline is the first of a new class of antibiotics named glycylcyclines and it was approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. Notwithstanding this, tigecycline's pharmacological and microbiological profile which includes multidrug-resistant pathogens encourages physicians' use of the drug in other infections. We analyzed, during the first months after its launch, the tigecycline prescriptions for 113 patients in 12 institutions. Twenty-five patients (22% received tigecycline for approved indications, and 88 (78% for "off label" indications (56% with scientific support and 22% with limited or without any scientific support. The most frequent "off label" use was ventilator associated pneumonia (VAP (63 patients. The etiology of infections was established in 105 patients (93%. MDR-Acinetobacter spp. was the microorganism most frequently isolated (50% of the cases. Overall, attending physicians reported clinical success in 86 of the 113 patients (76%. Our study shows that the "off label" use of tigecycline is frequent, especially in VAP. due to MDR-Acinetobacter spp., where the therapeutic options are limited (eg: colistin. Physicians must evaluate the benefits/risks of using this antibiotic for indications that lack rigorous scientific support.
Full Text Available Antimicrobial resistance surveillance is a standard measure in the sanitary policies. In order to monitor multi-resistance within APEC strains, a study was conducted on 370 broiler chickens farms from the Rabat-Salé-Zemmour-Zaer region in Morocco. The isolation of Escherichia coli was made from lesions of avian colibacillosis. Biochemical identification, serotyping and antimicrobial susceptibility tests as well as phenotypic identifications on lactamases resistance were carried out on the isolates. Serogrouping showed that 66.7 % of the isolates belong to the dominant serotypes O78, O 2 and O1. Drug sensitivity tests showed extremely high levels of resistance to oxytetracyclin (100 %, amoxicillin (90.9%, trimethoprim + sulphamethoxazol (82.2 %, enrofloxacin (75.9 % and florfenicol (61.5 %. Low frequencies of resistances were noted for gentamicin (24.8 %, fosfomycin (16.1 % and colistin (2%. In parallel, tests for the determination of the phenotype of resistance to beta-lactamases and cephalosporinases on 250 strains revealed that 66.1% of the strains were classified as class A penicillinases; 14.8% were class C cephalosporinases. The ESBL class A was found in 11.1% of the tested stains and only 3.7% were classified as wild-type strains. The multi-resistance is very high since 97.4% and 55.1% of the strains were respectively resistant to three and five antibacterial drugs.
Anyanwu, Madubuike Umunna; Okoye, Rosemary Chinazam
Antimicrobial resistance (AMR) is currently one of the major threats facing mankind. The emergence and rapid spread of multi- and pan-drug-resistant organisms (such as vancomycin-, methicillin-, extended-spectrum β-lactam-, carbapenem- and colistin-resistant organisms) has put the world in a dilemma. The health and economic burden associated with AMR on a global scale are dreadful. Available antimicrobials have been misused and are almost ineffective with some of these drugs associated with dangerous side effects in some individuals. Development of new, effective, and safe antimicrobials is one of the ways by which AMR burden can be reduced. The rate at which microorganisms develop AMR mechanisms outpaces the rate at which new antimicrobials are being developed. Medicinal plants are potential sources of new antimicrobial molecules. There is renewed interest in antimicrobial activities of phytochemicals. Nigeria boasts of a huge heritage of medicinal plants and there is avalanche of researches that have been undertaken to screen antimicrobial activities of these plants. Scientific compilation of these studies could provide useful information on the antimicrobial properties of the plants. This information can be useful in the development of new antimicrobial drugs. This paper reviews antimicrobial researches that have been undertaken on Nigerian medicinal plants. PMID:28512606
Gruber, Teresa M; Göttig, Stephan; Mark, Laura; Christ, Sara; Kempf, Volkhard A J; Wichelhaus, Thomas A; Hamprecht, Axel
To characterize a pan-drug-resistant Serratia marcescens clinical isolate carrying the New Delhi metallo-β-lactamase (NDM)-1. The presence of β-lactamase genes was examined by PCR and sequencing. Antibiotic susceptibility was determined by antibiotic gradient test. Transformation assays, transconjugation assays, PFGE and PCR-based replicon typing were used for plasmid analysis. Horizontal gene transfer was evaluated by liquid mating using Escherichia coli J53 as a recipient. Pathogenicity of NDM-1 expressing S. marcescens was analysed using the Galleria mellonella infection model. S. marcescens isolate SM1890 was non-susceptible to all tested antibiotics, with minocycline retaining intermediate activity. blaNDM-1 was located on a 140 kb IncA/C-type plasmid which was transferable to E. coli and Klebsiella pneumoniae by conjugation. The LD50 of the NDM-positive, SM1890 isolate was higher than that of other, NDM-1 negative, S. marcescens strains. The presence of a blaNDM-1-harbouring IncA/C plasmid resulted in marked resistance to β-lactam antibiotics, but had no significant effect on virulence of isogenic strains. Because of the intrinsic resistance of S. marcescens to colistin and reduced susceptibility to tigecycline, treatment options for infections by NDM-1-positive isolates are extremely limited in this species. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Osman, K M; Elhariri, M
The use of antibiotic feed additives in broiler chickens results in a high prevalence of resistance among their enteric bacteria, with a consequent emergence of antibiotic resistance in zoonotic enteropathogens. Despite growing concerns about the emergence of antibiotic-resistant strains, which show varying prevalences in different geographic regions, little work has been done to investigate this issue in the Middle East. This study provides insight into one of the world's most common and financially crippling poultry diseases, necrotic enteritis caused by Clostridium perfringens. The study was designed to determine the prevalence of antibiotic resistance in C. perfringens isolates from clinical cases of necrotic enteritis in broiler chickens in Egypt. A total of 125 isolates were obtained from broiler flocks in 35 chicken coops on 17 farms and were tested using the disc diffusion method. All 125 isolates were resistant to gentamicin, streptomycin, oxolinic acid, lincomycin, erythromycin and spiramycin. The prevalence of resistance to other antibiotics was also high: rifampicin (34%), chloramphenicol (46%), spectinomycin (50%), tylosin-fosfomycin (52%), ciprofloxacin (58%), norfloxacin (67%), oxytetracycline (71%), flumequine (78%), enrofloxacin (82%), neomycin (93%), colistin (94%), pefloxacin (94%), doxycycline (98%) and trimethoprim-sulfamethoxazole (98%). It is recommended that C. perfringens infections in Egypt should be treated with antibiotics for which resistant isolates are rare at present; namely, amoxicillin, ampicillin, cephradine, fosfomycin and florfenicol.
Chauvin, Claire; Beloeil, Pierre-Alexandre; Orand, Jean-Pierre; Sanders, Pascal; Madec, François
There is world-wide concern that antimicrobial use in food-producing animals might contribute to antimicrobial resistance both in animals and in humans. The relationship between antimicrobial use and resistance is likely to be related to frequency of prescription of the compound, dose and duration of treatment. Routine collection of that information is not possible today in France. A postal survey of French pig veterinarians therefore was carried out in October 2000. The questionnaire focused on the last antibiotic group-level prescription made; data were collected on the type of animals, presumptive clinical diagnosis and drug prescription. The list frame was defined using a veterinary yearbook. All practitioners with mention of pig in the treated species or with employment in intensive animal production were sent the questionnaire. Out of the 431 selected practitioners, 303 responded to the self-administered questionnaire (overall return proportion 70%). 159 prescriptions were received and analysed (response proportion 37%). Their repartitions according to indications and active compounds were summarised. Mean prescribed daily doses and mean treatment length were calculated for four antibiotics: amoxicillin, colistin, oxytetracycline, tylosin. Prescribed daily dose were in the range of dosages used and recommended in Europe. High variations were encountered in treatment length: from 3 to 21 days.
Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel
Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Full Text Available Abstract Background and Objectives: Increasing emergence of fluoroquinolone resistance among clinical isolates of Klebsiella pneumoniae (K. pneumoniae, has limited the treatment options for treatment of infections caused by these bacteria. The aim of this study was to investigate the dissemination of genes encoding AcrAB and QepA efflux pumps among K. pneumoniae strains. Methods: This study was carried out on 117 K. pneumoniae strains isolated from patients hospitalized in selected hospitals in Tehran city, 2015-2016, Iran. Antimicrobial susceptibility tests were performed using disk diffusion method (based on CLSI guidelines and identification of acr A, acr B and qep A genes using PCR assay. Results: In this study, colistin and tigecycline had the best effect against clinical isolates of K. pneumoniae. According to PCR results, 110 (94% isolates had acrA gene and 102 (87% isolates had acrB gene, respectively. The qepA gene was not found in any of the K. pneumoniae strains. Conclusion: According to the results of the present study, dissemination of the genes encoding AcrAB efflux pumps among K. pneumoniae strains, which cause resistance to fluoroquinolones, is a matter of concern. Therefore, infection control and prevention of the spread of drug-resistant bacteria requires careful management in drug prescription and identification of resistant isolates.
Soon, Rachel L.; Velkov, Tony; Chiu, Francis; Thompson, Philip E.; Kancharla, Rashmi; Roberts, Kade; Larson, Ian; Nation, Roger L.; Li, Jian
Fluorescence assays employing semi-synthetic or commercial dansyl-polymyxin B, have been widely employed to assess the affinity of polycations, including polymyxins, for bacterial cells and lipopolysaccharide (LPS). The five primary γ-amines on diaminobutyric-acid residues of polymyxin B are potentially derivatized with dansyl-cholride. Mass spectrometric analysis of the commercial product revealed a complex mixture of di- or tetra- dansyl-substituted polymyxin B. We synthesized a mono-substituted fluorescent derivative, dansyl[Lys]1polymyxinB3. The affinity of polymyxin for purified Gram-negative LPS, and whole bacterial cells was investigated. The affinity of dansyl[Lys]1polymyxinB3 for LPS was comparable to polymyxin B and colistin, and considerably greater (kd dansyl[Lys]1polymyxinB3 to LPS, attributed to electrostatic interactions. The hydrophobic dansyl moiety imparted a greater entropic contribution to the dansyl[Lys]1polymyxinB3-LPS reaction. Molecular modeling revealed a loss of electrostatic contact within the dansyl[Lys]1polymyxinB3-LPS complex due to steric hindrance from the dansyl[Lys]1 fluorophore; this corresponded with diminished antibacterial activity (MIC ≥ 16 μg/mL). Dansyl[Lys]1polymyxinB3 may prove useful as a screening tool for drug development. PMID:21050838
Pathak, S.P.; Gopal, K.
Bacterial populations in some organs, viz., liver, spleen, kidney, gill, and arborescent organ of the catfish Clarias batrachus were enumerated followed by determination of resistance for antibiotics and metals. The total viable counts in these organs, observed, were 2.24x10 4 , 2.08x10 4 , 1.44x10 4 , 1.23x10 4 , and 6.40x10 3 colony-forming units/mL, respectively. The random bacterial isolates from these fish organs showed resistance in decreasing order for colistin (98%), ampicillin (82%), gentamycin (34%), carbenicillin (28%), tetracyline (20%), streptomycin (12%), and ciprofloxacin (02%). Most of the isolates exhibited an increasing order of tolerance for the metals (μg/mL) copper (100), lead (200), manganese (400), cadmium (200), and chromium (50), with minimum inhibitory concentration (MIC) ranging from <50 to 1600 μg/mL. These observations indicate that the significant occurrence of bacterial population in organs of fish with high incidence of resistance for antibiotics and metals may pose risk to fish fauna and public health
Lin, M Y
Twenty-nine antibiotics or drugs were incorporated individually into mycoplasma agar to evaluate their inhibitory activity against avian mycoplasmas: 100 recent Taiwan isolates of 7 serotypes and 10 standard strains of 7 serotypes were tested. All of the standard strains were very sensitive to erythromycin, chlorotetracycline, doxycycline, minocycline, and tetracycline, but the local isolates were highly resistant to these antibiotics. The drugs or antibiotics that possessed an MIC90 of 50 micrograms/ml or less against the local isolates were tiamulin (less than 0.4 micrograms/ml), lincospectin (2.7), josamycin (2.7), lincomycin (3.0), spectinomycin (4.8), tylosin (6.0), kanamycin (6.0), chloramphenicol (6.0), gentamicin (7.5), apramycin (24.5), doxycycline (27.4), minocycline (29.0), spiramycin (30.0), colistin (44.3), leucomycin (45.0), and streptomycin (50.0). The MIC90 of the other antibiotics or drugs was greater than 50 micrograms/ml. None of the isolates or strains were sensitive to nalidixic acid, ronidazole, penicillin, ampicillin, cephalexin, carbadox, or four sulfa drugs at a concentration about 5 times the therapeutic level.
Full Text Available Abstract Background Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV. Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. Methods Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. Results All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: G. vaginalis strains were also susceptible for clindamycin ( 256 μg/ml but susceptible to clindamycin (0.023 – 0.125 μg/ml. Conclusion Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains.
Full Text Available Ettawa Grade (PE are potentially developed goats to produce milk and meat. Milk is food of animal that is rich in nutrients, but it is a perishable food easily contaminated by microorganisms. Contaminated pathogenic bacteria in milk can decrease the quality and has an organoleptic effect on milk, as well as endangers human health. Milk contaminated with bacteria antimicrobial resistance (AMR in which is resistant to antibiotics, may adversely affect the response to treatment with antibiotics in humans when suffering from infectious diseases and using antibiotics in therapy. In this study Ettawa Grade's samples of fresh milk and other dairy products were taken from some of the goat farms in Yogyakarta Sleman district. The samples were tested for the presence of pathogenic bacteria and for its resistance to several kinds of antibiotics. In this study 35 Ettawa Grade's samples of fresh milk and other dairy products (fresh milk, milk powder, ice cream, and yoghurt were taken from some of the goat farms in Sleman district-Yogyakarta. The samples were tested for the presence of pathogenic bacteria and for its resistance to several kinds of antibiotics. The result of the prevalence of pathogenic bacteria in goat fresh milk and other dairy products was 15% Escherichia coli and had multi resistance to multiple antibiotics, namely ampicillin, colistin sulphate, cefixime, kanamycin, oxytetracycline, tetracycline and sulfonamide.
Almani, Suhail Ahmed; Naseer, Ali; Maheshwari, Sanjay Kumar; Maroof, Pir; Naseer, Raza; Khoharo, Haji Khan
The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients. This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016. Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA). Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female ( P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii . Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin. The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.
Full Text Available We decipher the resistome of Chryseobacterium indologenes MARS15, an emerging multidrug-resistant clinical strain, using the whole genome sequencing strategy. The bacterium was isolated from the sputum of a hospitalized patient with cystic fibrosis in the Timone Hospital in Marseille, France. Genome sequencing was done with Illumina MiSeq using a paired-end strategy. The in silico analysis was done by RAST, the resistome by the ARG-ANNOT database and detection of polyketide synthase (PKS by ANTISMAH. The genome size of C. indologenes MARS15 is 4 972 580 bp with 36.4% GC content. This multidrug-resistant bacterium was resistant to all β-lactams, including imipenem, and also to colistin. The resistome of C. indologenes MARS15 includes Ambler class A and B β-lactams encoding blaCIA and blaIND-2 genes and MBL (metallo-β-lactamase genes, the CAT (chloramphenicol acetyltransferase gene and the multidrug efflux pump AcrB. Specific features include the presence of an urease operon, an intact prophage and a carotenoid biosynthesis pathway. Interestingly, we report for the first time in C. indologenes a PKS cluster that might be responsible for secondary metabolite biosynthesis, similar to erythromycin. The whole genome sequence analysis provides insight into the resistome and the discovery of new details, such as the PKS cluster.
Crofts, Terence S; Gasparrini, Andrew J; Dantas, Gautam
Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.
Cimmino, T; Rolain, J-M
We decipher the resistome of Chryseobacterium indologenes MARS15, an emerging multidrug-resistant clinical strain, using the whole genome sequencing strategy. The bacterium was isolated from the sputum of a hospitalized patient with cystic fibrosis in the Timone Hospital in Marseille, France. Genome sequencing was done with Illumina MiSeq using a paired-end strategy. The in silico analysis was done by RAST, the resistome by the ARG-ANNOT database and detection of polyketide synthase (PKS) by ANTISMAH. The genome size of C. indologenes MARS15 is 4 972 580 bp with 36.4% GC content. This multidrug-resistant bacterium was resistant to all β-lactams, including imipenem, and also to colistin. The resistome of C. indologenes MARS15 includes Ambler class A and B β-lactams encoding bla CIA and bla IND-2 genes and MBL (metallo-β-lactamase) genes, the CAT (chloramphenicol acetyltransferase) gene and the multidrug efflux pump AcrB. Specific features include the presence of an urease operon, an intact prophage and a carotenoid biosynthesis pathway. Interestingly, we report for the first time in C. indologenes a PKS cluster that might be responsible for secondary metabolite biosynthesis, similar to erythromycin. The whole genome sequence analysis provides insight into the resistome and the discovery of new details, such as the PKS cluster.
Patrícia Tomazini Medeiros
Full Text Available Probiotics and prebiotics were compared to antimicrobials as alternative growth promoters in male broilers grown from 1 to 42 days of age. Eight treatments were evaluated: a control feed without antimicrobials or alternative growth promoters, a control feed with antimicrobials, a control feed with the antimicrobials colistine and avilamicine, three rations with probiotic Bacillus subtilis in different concentrations and/or under recommended usage, one ration with probiotic Saccharomyces cerevisiae in addition to a mixture of probiotic Bacillus subtilis, Saccharomyces cerevisiae and Aspergillus oryzae, and one ration with mananoligossacarids (MOS plus betaglutanes. Antimicrobials and alternative growth promoters were added to an initial feed and to a growth feed common to all birds. Thirteen to 17 replicates of 50 birds of a Cobb line were utilized per treatment in a completely randomized design. Feed consumption, feed conversion and production costs did not significantly differ among treatments. The weights of 42-day-old birds fed on Bacillus subtilis (1,6 x 109CFU/g or the mixture of probiotics were higher or similar to the weights of birds fed on ration with antimicrobials. It was concluded that probiotics can replace antimicrobials as growth promoters for broilers up to 42 days of age without negative effects on growth performance and production cost.
Hubálek, Z; Scholz, H C; Sedlácek, I; Melzer, F; Sanogo, Y O; Nesvadbová, J
A systemic disease occurred in a wild population of the common vole Microtus arvalis in South Moravia (Czech Republic) during the years 1999-2003. Acute infections were characterized by edema of extremities, occasionally with colliquating abscesses, arthritis, lymphadenitis, perforations of the skin resulting from colliquated abscesses, orchitis, and peritoneal granulomas. From the clinical samples, small Gram-negative coccobacilli were isolated and identified as Ochrobactrum intermedium by API 20NE and colistin sensitivity profiles. However, subsequent rrs (16S rRNA) and recA (recombinase A) gene sequencing analysis of two isolates (CCM 4915=CAPM 6434; CCM 4916=CAPM 6435) identified them as Brucella sp. with sequence identities of 100% to other Brucella spp. Analysis of the omp2a/b genes confirmed the two isolates as Brucella. In AMOS polymerase chain reaction (PCR), a 2000-bp fragment was generated that was not seen in other brucellae. Experimental infection of outbred ICR mice with these isolates resulted in a mortality rate of 50%. Based on the results of the molecular investigations and the mortality observed in experimentally infected mice we conclude that the epizootic was caused by Brucella sp. and not by Ochrobactrum intermedium. The study demonstrates the limitations of commercial biochemical test systems in accurately differentiating among Ochrobactrum and Brucella.
Hameed P, Shahul; Manjrekar, Praveena; Chinnapattu, Murugan; Humnabadkar, Vaishali; Shanbhag, Gajanan; Kedari, Chaitanyakumar; Mudugal, Naina Vinay; Ambady, Anisha; de Jonge, Boudewijn L M; Sadler, Claire; Paul, Beena; Sriram, Shubha; Kaur, Parvinder; Guptha, Supreeth; Raichurkar, Anandkumar; Fleming, Paul; Eyermann, Charles J; McKinney, David C; Sambandamurthy, Vasan K; Panda, Manoranjan; Ravishankar, Sudha
The bacterial peptidoglycan biosynthesis pathway provides multiple targets for antibacterials, as proven by the clinical success of β-lactam and glycopeptide classes of antibiotics. The Mur ligases play an essential role in the biosynthesis of the peptidoglycan building block, N-acetyl-muramic acid-pentapeptide. MurC, the first of four Mur ligases, ligates l-alanine to UDP-N-acetylmuramic acid, initiating the synthesis of pentapeptide precursor. Therefore, inhibiting the MurC enzyme should result in bacterial cell death. Herein, we report a novel class of pyrazolopyrimidines with subnanomolar potency against both Escherichia coli and Pseudomonas aeruginosa MurC enzymes, which demonstrates a concomitant bactericidal activity against efflux-deficient strains. Radio-labeled precursor incorporation showed these compounds selectively inhibited peptidoglycan biosynthesis, and genetic studies confirmed the target of pyrazolopyrimidines to be MurC. In the presence of permeability enhancers such as colistin, pyrazolopyrimidines exhibited low micromolar MIC against the wild-type bacteria, thereby, indicating permeability and efflux as major challenges for this chemical series. Our studies provide biochemical and genetic evidence to support the essentiality of MurC and serve to validate the attractiveness of target for antibacterial discovery.
Rodrigo de Carvalho Santana
Full Text Available Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260. From 2007-2013, this percentage was 18.1% (965/5331. Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.
Uppu, Divakara S S M; Samaddar, Sandip; Ghosh, Chandradhish; Paramanandham, Krishnamoorthy; Shome, Bibek R; Haldar, Jayanta
Bacterial biofilms represent the root-cause of chronic or persistent infections in humans. Gram-negative bacterial infections due to nosocomial and opportunistic pathogens such as Acinetobacter baumannii are more difficult to treat because of their inherent and rapidly acquiring resistance to antibiotics. Due to biofilm formation, A. baumannii has been noted for its apparent ability to survive on artificial surfaces for an extended period of time, therefore allowing it to persist in the hospital environment. Here we report, maleic anhydride based novel cationic polymers appended with amide side chains that disrupt surface established multi-drug resistant A. baumannii biofilms. More importantly, these polymers significantly (p polymers also show potent antibacterial efficacy against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococci (VRE) and multi-drug resistant clinical isolates of A. baumannii with minimal toxicity to mammalian cells. We observe that optimal hydrophobicity dependent on the side chain chemical structure of these polymers dictate the selective toxicity to bacteria. Polymers interact with the bacterial cell membranes by causing membrane depolarization, permeabilization and energy depletion. Bacteria develop rapid resistance to erythromycin and colistin whereas no detectable development of resistance occurs against these polymers even after several passages. These results suggest the potential use of these polymeric biomaterials in disinfecting biomedical device surfaces after the infection has become established and also for the topical treatment of chronic bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available The aim of this study was to identify the antimicrobial susceptibility pattern and relevant treatment options in a neonatal intensive care unit from January 2012 and June 2016. Out of the total 78 culture positive samples, Gram positive and Gram negative microorganisms were 26% and 74% respectively. Acinetobacter remained the predominant isolate (32.1% followed by Klebsiella species (18.0%. Most of the Gram positive isolates exhibited higher resistance to penicillin, cephalosporin, macrolides, gentamycin and quinolones. Gram positive isolates had sensitivity of 100% to linezolid, vancomycin, chloramphenicol followed by rifampicin (84%. In comparison to other commonly used antibiotics, sensitivity to these four medicines was statistically significant (p<0.05. Similarly, most of the Gram negative bacteria showed resistance to cephalosporin, aminoglycosides. About two-third cases showed resistant to meropenum, quinolones and combination preparation of piperacillin and tazobactam. Overall sensitivity among the Gram negative isolates was to polymixin B (100% and minocycline (97%, followed by colistin (83%. In comparison to other commonly used antibiotics, sensitivity to these three medicines was statistically significant (p<0.05.
Hirsiger, P; Malik, J; Kommerlen, D; Vidondo, B; Arnold, C; Harisberger, M; Spring, P; Sidler, X
In the present study, risk factors for the use of oral antibiotics in weaned piglets were collected on 112 pig farms by a personal questionaire. The most common indication for an antibiotic group therapy was diarrhoea, and the most frequently used antibiotic was Colistin. On average, 27.33 daily doses in the control farms and 387.21 daily doses in the problem farms per 1000 weaners were administered on a given day. The significant risk factors in the multivariate model were poor hygiene in the water supply of suckling piglets, less than two doses ofprestarter feed daily, lack of an all-in-and-all-out production system in weaners, no herd book performance data analysis, and less than two of the legally prescribed veterinary visits per year. Furthermore, the treatment incidence of weaners for oral antibiotics was calculated on the basis of the drug inventory. This study provides evidence that the use of oral antibiotics in weaners can be reduced by interventions in hygiene and management.
Dong, Shao-Xing; Wang, Jann-Tay; Chang, Shan-Chwen
The majority of nosocomial infections in Taiwan hospitals are caused by drug-resistant Gram-negative bacteria (GNB), including Pseudomonas aeruginosa, Acinetobacter baumannii, and various species of Enterobacteriaceae. Carbapenems are important agents for treating infections caused by these GNB. Recently, doripenem was approved for use in Taiwan in August 2009. However, data on its in vitro activity against nosocomial GNB isolated from Taiwan remain limited. The study was designed to look into this clinical issue. A total of 400 nonduplicated nosocomial blood isolates isolated in 2009, inclusive of P. aeruginosa (n = 100), A. baumannii (n = 100), and Enterobacteriaceae (n = 200), were randomly selected from the bacterial bank preserved at National Taiwan University Hospital. Susceptibilities of these 400 isolates to various antibiotics, including doripenem, imipenem, meropenem, ceftazidime, amikacin, ciprofloxacin, colistin, and tigecycline were determined by using Etest. Doripenem demonstrated similar in vitro activity to imipenem and meropenem against P. aeruginosa (87%, vs. 85% and 89%), A. baumannii (56%, vs. 60% and 60%), and Enterobacteriaceae (100%, vs. 98.5% and 99.5%). The prevalence of carbapenem-resistant (any one of three tested carbapenems) P. aeruginosa, A. baumannii, and Enterobacteriaceae isolates was 15%, 44%, and 0.5%, respectively. Doripenem was as effective as imipenem and meropenem in our study. However, there was a significant proportion of carbapenem resistance among the tested isolates. Hence, longitudinal surveillance is necessary to monitor the resistance trend. Copyright © 2012. Published by Elsevier B.V.
Kidd, James M; Kuti, Joseph L; Nicolau, David P
Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP. Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed. Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.
Ammanamveetil A.M. Hatha
Full Text Available Finfish samples obtained from four retail outlets in Cochin between June 2009 and June 2010 were investigated for the occurrence of Vibrio parahaemolyticus. A total of 182 samples were collected and suspect isolates were identified using standard biochemical tests and were further confirmed by a species-specific tlh gene. V. parahaemolyticus was detected in 45.1% of samples, with demersal fish being more affected than pelagic species. The bacterium was isolated more frequently from the skin and gills of pelagic fish, while the intestine yielded greater numbers of V. parahaemolyticus in demersal fish. The highest incidence of antibiotic resistance was recorded against ampicillin and streptomycin, followed by carbenicillin, cefpodoxime, cephalothin, colistin and amoxycillin; the lowest was against nalidixic acid, tetracycline, chloramphenicol and ciprofloxacin. Multiple drug resistance was prevalent among isolates. Although only a fraction of strains are pathogenic for humans, the time-temperature abuse in markets provides ample scope for these strains to multiply to dangerous levels. The multidrug resistant nature of the strains adds to the gravity of the problem. High V. parahaemolyticus incidence rates in market finfish samples from areas in and around Cochin clearly indicates that control measures should be adopted to reduce post-harvest contamination in seafood and time-temperature abuse in markets to diminish the risk of V. parahaemolyticus infection associated with seafood destined for human consumption.
Mohammad Sadegh Rezai
Full Text Available Escherichia coli remains as one of the most important bacteria causing infections in pediatrics and producing extended-spectrum beta-lactamases (ESBLs making them resistant to beta-lactam antibiotics. In this study we aimed to genotype ESBL-producing E. coli isolates from pediatric patients for ESBL genes and determine their association with antimicrobial resistance. One hundred of the E. coli isolates were initially considered ESBL producing based on their MIC results. These isolates were then tested by polymerase chain reaction (PCR for the presence or absence of CTX, TEM, SHV, GES, and VEB beta-lactamase genes. About 30.5% of isolated E. coli was ESBL-producing strain. The TEM gene was the most prevalent (49% followed by SHV (44%, CTX (28%, VEB (8%, and GES (0% genes. The ESBL-producing E. coli isolates were susceptible to carbapenems (66% and amikacin (58% and showed high resistance to cefixime (99%, colistin (82%, and ciprofloxacin (76%. In conclusion, carbapenems were the most effective antibiotics against ESBl-producing E. coli in urinary tract infection in North of Iran. The most prevalent gene is the TEM-type, but the other resistant genes and their antimicrobial resistance are on the rise.
Anderson, Neil W; Buchan, Blake W; Riebe, Katherine M; Parsons, Lauren N; Gnacinski, Stacy; Ledeboer, Nathan A
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid method for the identification of bacteria. Factors that may alter protein profiles, including growth conditions and presence of exogenous substances, could hinder identification. Bacterial isolates identified by conventional methods were grown on various media and identified using the MALDI Biotyper (Bruker Daltonics, Billerica, MA) using a direct smear method and an acid extraction method. Specimens included 23 Pseudomonas isolates grown on blood agar, Pseudocel (CET), and MacConkey agar (MAC); 20 Staphylococcus isolates grown on blood agar, colistin-nalidixic acid agar (CNA), and mannitol salt agar (MSA); and 25 enteric isolates grown on blood agar, xylose lysine deoxycholate agar (XLD), Hektoen enteric agar (HE), salmonella-shigella agar (SS), and MAC. For Pseudomonas spp., the identification rate to genus using the direct method was 83% from blood, 78% from MAC, and 94% from CET. For Staphylococcus isolates, the identification rate to genus using the direct method was 95% from blood, 75% from CNA, and 95% from MSA. For enteric isolates, the identification rate to genus using the direct method was 100% from blood, 100% from MAC, 100% from XLD, 92% from HE, and 87% from SS. Extraction enhanced identification rates. The direct method of MALDI-TOF analysis of bacteria from selective and differential media yields identifications of varied confidence. Notably, Staphylococci spp. from CNA exhibit low identification rates. Extraction enhances identification rates and is recommended for colonies from this medium.
Zhang, Changsheng; Berra, Lorenzo; Klompas, Michael
In patients with ventilator-associated pneumonia, systemic use of antibiotics is the cornerstone of medical management. Supplemental use of aerosolized antibiotics with intravenous antibiotics in both experimental and clinical studies has been shown to have the following pharmacologic benefits: (1) aerosolized antibiotics reach the infected lung parenchyma without crossing the pulmonary alveolar capillary barrier; (2) aerosolized antibiotics increase anti-bacterial efficacy through increased local antibiotic concentration; and (3) aerosolized antibiotics decrease systemic toxicity. These benefits may be particularly beneficial to treat pneumonia caused by multidrug-resistant pathogens. Clinical data on the benefits of aerosolized antibiotics are more limited. Studies to date have not clearly shown improvements in time to extubation, mortality, or other patient-centered outcomes. At present, amikacin, colistin, and ceftazidime are the most frequently used and studied aerosolized antibiotics. This review summarizes the characteristics of aerosolized antibiotics, reviews the advantages and disadvantages of using aerosolized antibiotics, and calls for future investigations based on animal study data. Copyright © 2016 by Daedalus Enterprises.
Full Text Available Four groups each consisting in 440, 60 days old rabbits, were fed, respectively, four experimental diets: (1 MOS_0.5 (Bio-Mos® at 0.5 g/kg; (2 MOS_1.0 (Bio-Mos® at 1.0 g/kg; (3 MOS_ 1.5 (Bio-Mos® at 1.5 g/kg and (4 antibiotics (AGP, colistin sulphate 144 mg/kg; tylosin 100 mg/kg and oxytetracyclin 1000 mg/kg. Up to slaughter age (82 days of age mortality rate was recorded daily. For each group, 64 rabbits were controlled weekly for live weight to calculate daily weight gain (DWG. Feed intake (and, by consequence feed conversion ratio was measured, weekly, per group. At 82 days 16 rabbits per group were slaughtered and carcass traits were recorded. No differences were recorded among groups in live weight at different age and in daily weight gain but, in particular during the last week, AGP and MOS_0.5 groups showed higher feed intake and less favourable feed conversion ratio. MOS_1.0 group showed significantly higher incidence of empty gastro-intestinal tract but not differences were found for dressing out percentage. Perirenal fat showed a lower incidence in MOS than in AGP groups.
Abdalla, Nazar M; Osman, Amani A; Haimour, Waleed O; Sarhan, Mohammed A A; Mohammed, Mohammed N; Zyad, Eyhab M; Al-Ghtani, Abdalla M
This study aimed at evaluating the sensitivity of antibiotics towards nosocomial infections caused by Acinetobacter species. The study took place during the period Dec. 2011- Dec. 2012 at Assir Central Hospital in collaboration with the department of microbiology, college of medicine, King Khalid University, Abha. A prospective study involving 150 patients presented with nosocomial infections due to Acinetobacter species detected by bacteriological tests; direct microscopy, culture in blood agar media, fermentation test in MacConkey media and MIC (minimum inhibitory concentration) for antibiotics sensitivity using Muller Hinton media and Chemical test using API 20. A 150 nosocomial infections in this study showed gram-negative coccobacilli, non motile, glucose-negative fermentor and oxidase negative. All isolates showed 100% sensitivity to: Imipramine, Meropenem, Colistin. From the rest of tested antibiotics the higher resistant ones were; Nitrofurantoin 87% and Cefoxitin 85%. The least resistant antibiotics; Imipenem 3% and Ticarcillin 7%. While variable resistance in the rest of tested antimicrobials. A 47 patients (31.3%) have used antibiotics prior to this study. The high rate of usage occurred in elder patients. The frequency of Acinetobacter calcoaceticus baumannii complex multi-drugs resistance ABCMDR is rising including almost all commonly used antibiotics. Only few antibiotics exert 100% sensitivity towards these bacteria.
Vaz-Moreira, Ivone; Nunes, Olga C; Manaia, Célia M
Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water.
Vaz-Moreira, Ivone; Nunes, Olga C.; Manaia, Célia M.
Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water. PMID:21705522
Green, M; Wadowsky, R M; Barbadora, K
A cross-sectional survey of vancomycin-resistant gram-positive cocci (VRGPC) in the feces of children was initiated after several bacteremic infections with these organisms occurred at our hospital. A selective medium consisting of colistin-nalidixic acid agar, 5% sheep blood, vancomycin (5 mg/liter), and amphotericin B (8 mg/liter) was developed to isolate VRGPC. A single stool specimen submitted to the clinical microbiology laboratory from each of 48 patients was inoculated onto the medium. Plates were incubated at 35 degrees C with 5% carbon dioxide and examined at 24, 48, and 72 h. Susceptibilities were determined by broth microdilution. A total of 14 isolates from 11 of 48 (22%) children were recovered. The density of growth ranged from a single colony to 2+. The VRGPC were identified as Leuconostoc lactis (n = 2), Lactobacillus confusus (n = 4), Enterococcus species (n = 5), and Lactococcus lactis (n = 3). One strain of Lactobacillus confusus was recovered from both the stool and the blood of one of these patients. The MICs of vancomycin were 4 micrograms/ml for one of the isolates, 8 micrograms/ml for four of the isolates, and more than 16 micrograms/ml for the remaining eight isolates. All isolates were susceptible to both penicillin and ampicillin. Only 1 of the 11 children had received prior treatment with vancomycin. We conclude that low concentrations of VRGPC may be common in the gastrointestinal tracts of children.
Adelowo, Olawale O; Fagade, Obasola E; Agersø, Yvonne
This study investigated the mechanisms of resistance in 36 E. coli isolated from waste, litter, soil and water samples collected from poultry farms in Southwestern Nigeria. Minimum inhibitory concentration (MIC) distributions of the isolates were determined using the methods of the Clinical and Laboratory Standard Institute and resistance genes detected by PCR. A total of 30 isolates (94%) showed resistance to more than one antimicrobial. Percentage resistance was: tetracycline 81%, sulphamethoxazole 67%, streptomycin 56%, trimethoprim 47 %, ciprofloxacin 42%, ampicillin 36%, spectinomycin 28%, nalidixic acid 25%, chloramphenicol 22%, neomycin 14%, gentamicin 8%, amoxicillin-clavulanate, ceftiofur, cefotaxime, colistin, florfenicol and apramycin 0%. Resistance genes found among the isolates include bla-TEM (85%), sul2 (67%), sul3 (17%), aadA (65%), strA (70%), strB (61%), catA1 (25%), cmlA1 (13%), tetA (21%) and tetB (17%). Class 1 and 2 integrons were found in five (14%) and six (17%) isolates, respectively, while one isolate was positive for both classes of integrons. Seven out of eight isolates with resistance to ciprofloxacin and MIC ≤ 32 mg/L to nalidixic acid contained qnrS genes. Our findings provided additional evidence that the poultry production environment in Nigeria represents an important reservoir of antibiotic resistance genes such as qnrS that may spread from livestock production farms to human populations via manure and water.
Chao, M-R; Hsien, C-H; Yeh, C-M; Chou, S-J; Chu, C; Su, Y-C; Yu, C-Y
Salmonella enterica causes a number of significant poultry diseases and is also a major pathogen in humans. Most poultry infected by Salmonella become carriers; infection may also be fatal, depending on the particular serovar and the age of the bird at infection. Younger birds are more susceptible to infection by Salmonella, so it is critical that hatcheries monitor birds. We developed a method to use hatched eggshell membranes (HEM) to assess contamination by Salmonella in poultry hatching cabinets and to evaluate the prevalence of Salmonella in a goose hatchery and rearing farm. Comparison of the Salmonella isolation rate in hatching cabinets using 3 sampling methods showed that the highest Salmonella contamination was detected in HEM, and that these results differed significantly from those obtained from fluff samples and cabinet swab samples (P chicken, and duck hatcheries. The lowest Salmonella-positive rate was found for the chicken hatchery, followed by the goose and the duck hatcheries (P hatcheries: A, B, C1, C2, D, and E. The distribution of these serogroups differed among the hatcheries. Salmonella serogroup C1 was the major serogroup found in geese, compared with serogroup B in chickens and ducks. However, Salmonella Typhimurium was dominant in 1 goose hatchery and also in geese from this hatchery that had been transferred to a farm. Antibiotic susceptibility analysis showed that Salmonella Typhimurium strains isolated from the farm geese with diarrhea showed significantly higher resistance to doxycycline, colistin, sulfamethoxazole-trimethoprin, and cephalothin than those isolated from the hatchery (P hatcheries and rearing farms.
Arilson Santos da Paz
Full Text Available The effect of the use of prebiotics, organic acids and probiotics on the performance and the cuts yield of broilers was evaluated in birds from 8 to 21 and from 22 to 43 days of age. It was used a completely randomized design, with 6 treatments and 4 replications, with 20 male Cobb chicks in the initial phase and 24 in the growth phase per experimental unit, totaling 1056 birds. The additives used in the treatments were: antibiotics (avilamycin and colistin, prebiotic (mannanoligosaccharides, prebiotic plus organic acids (fumaric and propionic, probiotic (Bacillus subtillis and commercial mixture of probiotics (Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum, Streptococcus thermophilus, Enterococcus faecium. No differences were found among treatments for the variables studied in the initial phase, but, in the growth phase, the birds that received treatment with prebiotic plus organic acids presented better feed:gain ratio than those received only prebiotic. Those which received the mixture of probiotics showed better breast yield than those received the basal diet without additives. It was concluded that mannanoligosaccharides, whether combined or not with organics fumaric and propionic acids, and probiotics can replace the antibiotics avilamycin and colistin in rations of broilers without loss of performance.Avaliou-se o efeito do uso de prebióticos, ácidos orgânicos e probióticos em dietas de frangos de corte, com 8 a 21 e 22 a 43 dias de idade, sobre o desempenho e o rendimento de cortes. Usou-se o delineamento inteiramente casualizado, com 6 tratamentos e 4 repetições, com 20 pintos machos Cobb na fase inicial e 24 na de crescimento por unidade experimental, num total de 1056 aves. Os aditivos usados nos tratamentos foram: antibióticos (avilamicina e colistina, prebiótico (mananoligossacarídeos, prebiótico mais ácidos orgânicos (fumárico e propi
Caltagirone, Mariasofia; Bitar, Ibrahim; Piazza, Aurora; Spalla, Melissa; Nucleo, Elisabetta; Navarra, Antonella; Migliavacca, Roberta
A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing a heart transplantation at the Acute Care Hospital I.R.C.C.S. S. Matteo of Pavia. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient's preputial swab. Both the K. oxytoca and C. koseri strains were carbapenem- resistant by MicroScan System (Beckman Coulter). Carbapenem-resistant K. pneumoniae had previously been reported in the same rehabilitation facility. The aim of the study was to identify the carbapenem resistance mechanisms among the enterobacterial species recovered. Phenotypic screening tests useful to detect the β-lactamases/carbapenemases were performed. Carbapenem MICs were obtained by Etest. AmpC and MBL encoding genes were identified by PCR and sequencing. Conjugation assays and plasmid characterization were performed. Both of the K. oxytoca and C. koseri isolates were multi drug resistant, showing resistance to amoxicillin-clavulanic acid, three generation cephalosporins, ertapenem (K. oxytoca MIC, >32 mg/L; C. koseri MIC, 4 mg/L), imipenem (K. oxytoca MIC, 4 mg/L; C. koseri MIC, 12 mg/L), thrimethoprim sulphamethoxazole and gentamicin. Susceptibility was retained to fluoroquinolones, colistin and tigecycline. Molecular characterization confirmed the co-presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes.
Gao, Lei; Lyu, Yuan; Li, Yun
Acinetobacter baumannii has emerged as an important pathogen causing a variety of infections. Using data from the China Surveillance of Antimicrobial Resistance Program conducted biennially, we investigated the secular changes in the resistance of 2917 isolates of A. baumannii from 2004 to 2014 to differ antimicrobial agents. Pathogen samples were collected from 17 to 20 hospitals located in the eastern, central, and western regions of China. Minimum inhibitory concentrations (MICs) were determined by a 2-fold agar dilution method, and antimicrobial susceptibility was established using the 2014 Clinical Laboratory Standards Institute-approved breakpoints. Isolates not susceptible to all the tested aminoglycosides, fluoroquinolones, β-lactams, β-lactam/β-lactam inhibitors and carbapenems were defined as extensively drug resistant. The rates of nonsusceptibility to common antimicrobial agents remained high (>65%) over the years with some fluctuations to certain agents. The prevalence of imipenem-resistant A. baumannii (IRAB) increased from 13.3% in 2004 to 70.5% in 2014 and that of extensively drug-resistant A. baumannii (XDRAB) increased from 11.1% in 2004 to 60.4% in 2014. The activity of tigecycline was stable with MIC90 ≤4 mg/L against A. baumannii from 2009 to 2014. Susceptibility to colistin remained high (97.0%) from 2009 to 2014. The prevalence of XDRAB increased in all the three surveillance regions over the years and was significantly higher in Intensive Care Unit (ICU) wards than non-ICU wards. This longitudinal multicenter surveillance program revealed the nationwide emergence of A. baumannii in China and showed a significant increase in prevalence from 2004 to 2014. High levels of bacterial resistance were detected among samples collected from clinical settings in China, with IRAB and XDRAB being especially prevalent. This study will help to guide empirical therapy and identify at-risk groups requiring more intense interventional infection control
Purighalla, Swathi; Esakimuthu, Sarita; Reddy, Mallika; Varghese, George K; Richard, Vijay S; Sambandamurthy, Vasan K
The purpose of this study was to evaluate the discriminatory power of two DNA-based technique and a protein-based technique for the typing of nosocomial isolates of Klebsiella pneumoniae. A second objective was to determine the antimicrobial susceptibility pattern and characterise the presence of genes encoding extended-spectrum beta-lactamases (ESBLs) and carbapenemases. Forty-six K. pneumoniae isolates from patients with bloodstream infections at a tertiary care hospital in India between December 2014 and December 2015 were studied. All isolates were typed using enterobacterial repetitive intergenic consensus sequence-polymerase chain reaction (ERIC-PCR), randomly amplified polymorphic DNA (RAPD) analysis and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry. Antimicrobial susceptibility profiles and ESBLs were detected using the BD Phoenix system. The types of ESBL and carbapenemase genes present were detected using PCR. Isolates were subtyped into 31, 30 and 33 distinct genotypes by ERIC-PCR, RAPD and MALDI-TOF, respectively. Several isolates displaying identical DNA fingerprints were binned into different branches based on their proteomic fingerprint. Antimicrobial susceptibility tests revealed that 33/46 strains were multidrug resistant (MDR); a majority of the strains (83%) were sensitive to colistin. PCR-based analysis demonstrated 19 strains to harbour two or more ESBL and carbapenemase genes. ERIC-PCR was the most reproducible method for typing K. pneumoniae isolates and could not be substituted by MALDI-TOF for clonality analysis. A high degree of genetic diversity and the presence of MDR genes highlight the challenges in treating K. pneumoniae-associated infections.
Full Text Available Purpose: The purpose of this study was to evaluate the discriminatory power of two DNA-based technique and a protein-based technique for the typing of nosocomial isolates of Klebsiella pneumoniae. A second objective was to determine the antimicrobial susceptibility pattern and characterise the presence of genes encoding extended-spectrum beta-lactamases (ESBLs and carbapenemases. Materials and Methods: Forty-six K. pneumoniae isolates from patients with bloodstream infections at a tertiary care hospital in India between December 2014 and December 2015 were studied. All isolates were typed using enterobacterial repetitive intergenic consensus sequence-polymerase chain reaction (ERIC-PCR, randomly amplified polymorphic DNA (RAPD analysis and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF mass spectrometry. Antimicrobial susceptibility profiles and ESBLs were detected using the BD Phoenix system. The types of ESBL and carbapenemase genes present were detected using PCR. Results: Isolates were subtyped into 31, 30 and 33 distinct genotypes by ERIC-PCR, RAPD and MALDI-TOF, respectively. Several isolates displaying identical DNA fingerprints were binned into different branches based on their proteomic fingerprint. Antimicrobial susceptibility tests revealed that 33/46 strains were multidrug resistant (MDR; a majority of the strains (83% were sensitive to colistin. PCR-based analysis demonstrated 19 strains to harbour two or more ESBL and carbapenemase genes. Conclusion: ERIC-PCR was the most reproducible method for typing K. pneumoniae isolates and could not be substituted by MALDI-TOF for clonality analysis. A high degree of genetic diversity and the presence of MDR genes highlight the challenges in treating K. pneumoniae-associated infections.
Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W
Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.
Full Text Available The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE represent a major public health concern because these bacteria are usually extensively resistant to most antibiotics. In order to evaluate their dissemination in Quebec, a surveillance program was introduced in 2010. We report the molecular and epidemiological profiles of CPE isolates collected. Between August 2010 and December 2012, a total of 742 non-duplicate isolates non-susceptible to carbapenems were analysed. AmpC β-lactamase and metallo-β-lactamase production were detected by Etest and carbapenemase production by the modified Hodge test (MHT. Antibiotic susceptibility profiles were determined using broth microdilution or Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC strains was analyzed by pulsed-field gel electrophoresis (PFGE. The presence of genes encoding carbapenemases as well as other β-lactamases was detected using PCR. Of the 742 isolates tested, 169 (22.8% were CPE. Of these 169 isolates, 151 (89.3% harboured a blaKPC gene while the remaining isolates carried blaSME (n = 9, blaOXA-48 (n = 5, blaNDM (n = 3, and blaNMC (n = 1 genes. Among the 93 KPC strains presenting with a unique pattern (unique PFGE pattern and/or unique antibiotics susceptibility profile, 99% were resistant to ertapenem, 95% to imipenem, 87% to meropenem, 97% to aztreonam, 31% to colistin and 2% to tigecycline. In 19 patients, 2 to 5 KPC strains from different species or with a different PFGE pattern were isolated. CPE strains were present in the province of Quebec with the majority of strains harbouring KPC. Alternately, SME, OXA-48 and NMC containing strains were rarely found.
Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G
The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.
Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d.
Tang, Zhiru; Yin, Yulong; Zhang, Youming; Huang, Ruilin; Sun, Zhihong; Li, Tiejun; Chu, Wuying; Kong, Xiangfeng; Li, Lili; Geng, Meimei; Tu, Qiang
Lactoferrin has antimicrobial activity associated with peptide fragments lactoferricin (LFC) and lactoferrampin (LFA) released on digestion. These two fragments have been expressed in Photorhabdus luminescens as a fusion peptide linked to protein cipB. The construct cipB-LFC-LFA was tested as an alternative to antimicrobial growth promoters in pig production. Sixty piglets with an average live body weight of 5.42 (sem 0.59) kg were challenged with enterotoxigenic Escherichia coli and randomly assigned to four treatment groups fed a maize-soyabean meal diet containing either no addition (C), cipB at 100 mg/kg (C+B), cipB-LFC-LFA at 100 mg/kg (C+L) or colistin sulfate at 100 mg/kg (C+CS) for 3 weeks. Compared with C, dietary supplementation with C+L for 3 weeks increased daily weight gain by 21 %, increased recovery from diarrhoea, enhanced serum glutathione peroxidase (GPx), peroxidase (POD) and total antioxidant content (T-AOC), liver GPx, POD, superoxide dismutase and T-AOC, Fe, total Fe-binding capacity, IgA, IgG and IgM levels (P < 0.05), decreased the concentration of E. coli in the ileum, caecum and colon (P < 0.05), increased the concentration of lactobacilli and bifidobacteria in the ileum, caecum and colon (P < 0.05), and promoted development of the villus-crypt architecture of the small intestine. Growth performance was similar between C+L- and C+CS-supplemented pigs. The present results indicate that LFC-LFA is an effective alternative to the feed antibiotic CS for enhancing growth performance in piglets weaned at age 21 d.
Abi Khattar, Z.; Gaudriault, S.; Givaudan, A.
Lipid A is a potent endotoxin, and its fatty acids (lauric, myristic, and sometimes palmitic acid) anchors lipopolysaccharide (LPS) into the outer leaflet of the outer membrane of most Gram-negative bacteria. The highly anionic charge of the glucosamine lipid A moiety makes the LPS a powerful attractant for cationic antimicrobial peptides (AMPs). AMPs are major component of innate immunity that kill bacteria by permeabilization of lipid bilayers. Secondary lipid A acylation of Klebsiella pneumoniae, involving the acyltransferase LpxM (formally, msbBor WaaN) that acylates (KDO)2-(lauroyl)-lipid IV-A with myristate during lipid A biosynthesis, has been associated with bacterial resistanceto AMPs contributing to virulence in animal models. We investigated here the role of the msbB gene of the entomopathogenic bacterium Photorhabdus luminescens in AMP resistance, by functional complementation of the AMP susceptible K. pneumoniae lpxM mutant with the P. luminescens msbB gene. We showed that msbB (lpxM) gene of P. luminescensis able to enhance polymyxin B, colistin and cecropin A resistance of K. pneumoniae lpxM mutant, compared to the non-complemented mutant. However, we could not obtain any msbB mutant of Photorhabdus by performing allelic exchange experiments based on positive selection of sucrose highly resistant mutants.We thus suggest that msbB-mediated Photorhabdus lipid A acylation is essential for outer membrane low-permeability and thatmodification of lipid A composition, fluidity and osmosis-resistance have an important role in the ability of Photorhabdus to grow in sucrose at high concentrations. (author)
Rana, Namrata; Jesse, Helen E; Tinajero-Trejo, Mariana; Butler, Jonathan A; Tarlit, John D; von Und Zur Muhlen, Milena L; Nagel, Christoph; Schatzschneider, Ulrich; Poole, Robert K
Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ 3 N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ 3 N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ 3 N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ 3 N)]Br.
Gayosso-Vázquez, Catalina; Fernández-Vázquez, José Luis; Jarillo-Quijada, Ma Dolores; Rivera-Benítez, César; Santos-Preciado, José Ignacio
Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrophoresis. The ability to form biofilm was determined on a polystyrene surface. The resistance to complement was determined with a pooled human normal serum and TNFα release by infected macrophages was determined by ELISA. The 112 isolates from this study were associated with a 52% of mortality. All were resistance to β-lactams, fluoroquinolones, and trimethroprim-sulfamethoxal, 96 and 90% were resistant to meropenem and imipenem, respectively, but with high susceptibility to polymyxin B, colistin and tigecyclin. Isolates were classified in 11 different clones. Most isolates, 88% (99/112), were metallo-β-lactamases and carbapenemases producers, associated in 95% with the presence of blaOXA-72 gene. Only 4/99 and 1/99 of the carbapenem-resistant isolates were related to efflux mechanism to meropenem or imipenem resistance, respectively. The loss of expression of 22, 29, and/or 33-36-kDa proteins was detected in 8/11 of the clinical isolates with resistance to carbapenem. More than 96% (108/112) of the isolates were high producers of biofilms on biotic surfaces. Finally, all isolates showed variable resistance to normal human serum activity and were high inductors of TNFα release by macrophages. In summary, these results suggest that multidrug-resistant A. baumannii can persist in the hospital environment through its ability to form biofilms. The high mortality observed was due to their ability to survive normal human serum activity and capability to induce potent
Maspi, Hossein; Mahmoodzadeh Hosseini, Hamideh; Amin, Mohsen; Imani Fooladi, Abbas Ali
Acinetobacter species particularly Acinetobacter baumannii (A. baumannii) have been widely reported as broad-spectrum antibiotic resistant pathogens. Expression of various types of metallo beta-lactamases (MBL), classified as Ambler class B, has been associated with carbapenem resistance. Here, we attempted to assess the frequency of extensively drug-resistant (XDR) and MBL-producing A. baumannii among clinical isolates. 86 clinical A. baumannii strains were collected from 2014 to 2015 and their susceptibility to meropenem (10 μg), imipenem (10 μg), azteronem (30 μg), pipracillin (100 μg) tazobactam (110 μg), tobramycin (10 μg), fosfomycin (200 μg), rifampicin (5 μg), colistin (10 μg), tigecycline (15 μg), sulbactam/ampicillin (10 μg + 10 μg) and polymixin B (300 U) was evaluated using disk diffusion method. The MBL-producing isolates were screened using combined disc diffusion method. Furthermore, the presence of blaVIM, blaIMP, blaSPM, blaGIM, blaSIM and blaNDM was detected by PCR. 34.9% of isolates were recovered from bronchoalveolar lavage (BAL). 81 (94.2%) and 62 (71.2%) isolates were multidrug resistance (MDR) and XDR, respectively. 44 (51.2%) and 65 (75.6%) isolates were MBL-producing strains with resistance to imipenem and meropenem, respectively. 2 (2.3%), 13 (15.1%), 2 (2.3%), 4 (4.7%) and 2 (2.3%) isolates carried blaVIM, blaIMP, blaSPM, blaGIM and blaSIM genes, respectively. Our data showed that the rate of XDR and MBL A. baumannii is on the rise. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yang, Ming-Yeh; Chang, Kai-Chih; Chen, Liang-Yu; Wang, Po-Ching; Chou, Chih-Chiang; Wu, Zhong-Bin; Hu, Anren
Photodynamic inactivation (PDI) is a non-invasive and safe therapeutic method for microbial infections. Bacterial antibiotic resistance is caused by antibiotics abuse. Drug-resistant Acinetobacter spp. is a serious problem in hospitals around the world. These pathogens from nosocomial infections have high mortality rates in frailer people, and Acinetobacter spp. is commonly found in immunocompromised patients. Visible light is safer than ultraviolet light (UV) for PDI of nosocomial pathogens with mammalian cells. Zinc oxide nanoparticles (ZnO-NPs) were used in this study as an antimicrobial agent and a photosensitizer. ZnO is recognized as safe and has extensive usage in food additives, medical and cosmetic products. In this study, we used 0.125 mg/ml ZnO-NPs combined with 10.8 J/cm 2 blue light (BL) on Acinetobacter baumannii (A. baumannii) that could significantly reduce microbial survival. However, individual exposure to ZnO-NPs does not affect the viability of A. baumannii. BL irradiation could trigger the antimicrobial ability of ZnO nanoparticles on A. baumannii. The mechanism of photocatalytic ZnO-NPs treatment for sterilization occurs through bacterial membrane disruptions. Otherwise, the photocatalytic ZnO-NPs treatment showed high microbial eradication in nosocomial pathogens, including colistin-resistant and imipenem-resistant A. baumannii and Klebsiella pneumoniae. Based on our results, the photocatalytic ZnO-NPs treatment could support hygiene control and clinical therapies without antibiotics to nosocomial bacterial infections. Copyright © 2018. Published by Elsevier B.V.
Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu
This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Modarresi, Farzan; Azizi, Omid; Shakibaie, Mohammad Reza; Motamedifar, Mohammad; Valibeigi, Behnaz; Mansouri, Shahla
Resistance-nodulation-division efflux system (RND) adeABC contributes to intrinsic resistance to various drug classes in Acinetobacter baumannii. Similarly, quorum sensing (QS) plays an important role in the biofilm formation and pathogenicity of this bacterium. The aims of this study were to evaluate the influence of iron limitation on the expression of efflux pump (adeABC) genes and QS (luxI, luxR) system by relative quantitative real-time polymerase chain reaction (qRT-PCR). In addition, DNA sequence and phylogenetic relatedness of biofilm-associated protein (Bap) gene was also investigated. Sixty-five multidrug-resistant isolates of A. baumannii were recovered from ICU patients of three hospitals in Kerman, Iran. The isolates were highly resistant to at least 11 antibiotics (MIC ≥64 μg/mL); however, 87% and 89% were susceptible to colistin and tigecycline, respectively (MIC 0.05 μg/mL) (p ≤ 0.05). We detected the presence of RND efflux pump, QS, and bap genes with the frequencies of 92% (adeA), 61.5% (adeB), 84.6% (adeC), 80% (luxI), 61% (luxR), and 66% (bap), respectively. qRT-PCR analysis showed that in some isolates, expression of both adeABC and luxI/R was increased more than fourfold in the presence of low iron (20 μm), suggesting the additional regulatory role of iron on both efflux pump and QS system. Alignment and phylogenetic analysis on the strong biofilm forming isolates confirmed that the fragments amplified were indeed part of bap gene and deduced sequence was similar to A. baumannii K9B410. © 2015 APMIS. Published by John Wiley & Sons Ltd.
Seruga Music, M; Hrenovic, J; Goic-Barisic, I; Hunjak, B; Skoric, D; Ivankovic, T
Acinetobacter baumannii is a leading emerging pathogen that is frequently recovered from patients during hospital outbreaks. The role of environmental A. baumannii reservoirs is therefore of great concern worldwide. To investigate the connection between A. baumannii causing hospital outbreaks and environmental isolates from hospital wastewater, urban sewage and river water as the final natural recipient of wastewaters. Clinical isolates from patients with hospital-acquired pneumonia and environmental isolates from water were collected during a two-month monitoring period. Recovery of A. baumannii was performed using CHROMagar Acinetobacter plates, incubated at 42°C for 48 h. Identification was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry and analyses of rpoB gene. The antibiotic resistance profiles were interpreted according to criteria given for clinical isolates of A. baumannii. The sequence types (ST) were retrieved by multi-locus sequence typing. Fourteen of 19 isolates recovered from patients, hospital wastewaters, urban sewage and river water belonged to ST-195. The remaining five isolates recovered from patients and river water were assigned to ST-1421. All isolates showed very strong relatedness and clustered into CC92, which corresponds to IC2. All isolates were non-susceptible to at least one agent in all but two or fewer antimicrobial categories, and thus were classified as 'extensively-drug-resistant' (XDR). Heteroresistance to colistin was found in two isolates from hospital wastewater. Close relatedness of clinical and environmental isolates suggests the emission of XDR A. baumannii via the untreated hospital wastewater in the natural environment. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Tan, Sean Yang-Yi; Chua, Song Lin; Liu, Yang; Høiby, Niels; Andersen, Leif Percival; Givskov, Michael; Song, Zhijun; Yang, Liang
The emergence of extreme-drug-resistant (EDR) bacterial strains in hospital and nonhospital clinical settings is a big and growing public health threat. Understanding the antibiotic resistance mechanisms at the genomic levels can facilitate the development of next-generation agents. Here, comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU within a 1-month interval. Multilocus sequence typing indicates that these two isolates belonged to ST208. The A. baumannii 53264 strain gained colistin resistance compared with the 48055 strain and became an EDR strain. Genome sequencing indicates that A. baumannii 53264 and 48055 have almost identical genomes—61 single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii 53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135 contigs, with a total length of 4,049,562 bp with 39.00% GC content. Genome comparisons showed that this A. baumannii clone is classified as an International clone II strain and has 94% synteny with the A. baumannii ACICU strain. The ResFinder server identified a total of 14 antibiotic resistance genes in the A. baumannii clone. Proteomic analyses revealed that a putative porin protein was down-regulated when A. baumannii 53264 was exposed to antimicrobials, which may reduce the entry of antibiotics into the bacterial cell. PMID:23538992
Ghaith, Doaa Mohammad; Zafer, Mai Mahmoud; Al-Agamy, Mohamed Hamed; Alyamani, Essam J; Booq, Rayan Y; Almoazzamy, Omar
Acinetobacter baumannii is known for nosocomial outbreaks worldwide. In this study, we aimed to investigate the antibiotic susceptibility patterns and the clonal relationship of A. baumannii isolates from the intensive care unit (ICU) of an Egyptian hospital. In the present study, 50 clinical isolates of multidrug resistant (MDR)-A. baumannii were obtained from patients admitted into the ICU from June to December 2015. All isolates were analyzed for antimicrobial susceptibilities. Multiplex PCR was performed to detect genes encoding oxacillinase genes (bla OXA-51 -like, bla OXA-23 -like, bla OXA-24 -like, and bla OXA-58 -like). Multilocus sequence typing (MLST) based on the seven-gene scheme (gltA, gyrB, gdhB, recA, cpn60, gpi, rpoD) was used to examine these isolates. All A. baumannii clinical isolates showed the same resistance pattern, characterized by resistance to most common antibiotics including imipenem (MIC ≥ 8μ/mL), with the only exception being colistin. Most isolates were positive for bla OXA-51 -like and bla OXA-23 -like (100 and 96%, respectively); however, bla OXA-24 -like and bla OXA-58 -like were not detected. MLST analysis identified different sequence types (ST195, ST208, ST231, ST441, ST499, and ST723) and a new sequence type (ST13929) with other sporadic strains. MDR A. baumannii strains harboring bla OXA-23 -like genes were widely circulating in this ICU. MLST was a powerful tool for identifying and epidemiologically typing our strains. Strict infection control measures must be implemented to contain the worldwide spread of MDR A. baumannii in ICUs.
Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical
Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies. PMID:23917322
Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel
Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii
Ghaddar, Nahed; Alfouzan, Wadha; Anastasiadis, Elie; Al Jiser, Tamima; Itani, Saad Eddine; Dernaika, Racha; Eid, Toufic; Ghaddar, Ali; Charafeddine, Adib; Dhar, Rita; El Hajj, Hiba
This study was undertaken to evaluate chromogenic medium and a direct latex agglutination test (DLA) for detection of Group B Streptococcus (GBS) in the vaginal specimens of pregnant women, and to ascertain the prevalence of GBS in this population in Kuwait and Lebanon. Vaginal swabs, collected from women at 35-37 weeks of gestation, were cultured on 5 % sheep blood agar (SBA), colistin nalidixic acid agar (CNA), Strept B Select chromogenic agar (SBS) as well as Lim enrichment broth in 168 cases in Lebanon while only SBA was used for 1391 samples in Kuwait. In addition, vaginal samples from 102 GBS-positive and 20 GBS-negative women near the time of delivery were collected in Kuwait for evaluation of the DLA test. During the study period, the prevalence of GBS colonization was determined to be 20.7 % (288/1391) in Kuwait while 18.4 % (31) of 168 pregnant women in Lebanon had vaginal cultures positive for GBS. By direct plating of vaginal swabs on the three media used, the isolation rates of GBS were 51.6, 64.5 and 77.4 % on SBA, CNA and SBS, respectively, which increased to 90.35, 93.1 and 96.8 %, respectively, following subculture in Lim broth after 18 h of incubation. The sensitivity of the DLA test was found to be dependent on the density of GBS colonization, resulting in 100 % sensitivity and 100 % specificity for heavy (>10(2) c.f.u. per swab) and moderately heavy (50-100 c.f.u. per swab) growth of GBS. However, for vaginal specimens yielding women. The DLA test, in particular, could prove to be a useful tool for immediate detection of GBS in women near delivery so that intrapartum antibiotic prophylaxis can be initiated. © 2014 The Authors.
Farsiani, Hadi; Mosavat, Arman; Soleimanpour, Saman; Nasab, Mahbobeh Naderi; Salimizand, Himen; Jamehdar, Saeid Amel; Ghazvini, Kiarash; Aryan, Ehsan; Baghani, Ali-Asghar
This study determined the mechanisms and patterns of antimicrobial resistance among the isolates obtained from different wards of a teaching hospital in the city of Mashhad in north-east Iran. Between January 2012 and the end of June 2012, 36 isolates of Acinetobacter baumannii were collected from different wards of Ghaem Hospital. Antimicrobial susceptibility testing and epsilometer testing (E-test) were performed. The genetic resistance determinants of A, B and D classes of β-lactamases, aminoglycoside modifying enzymes (AMEs), efflux pumps and ISAba1 elements were assessed by PCR. Repetitive extragenic palindromic element (REP)-PCR was performed to find the genetic relatedness of the isolates. Colistin was the most effective antibiotic of those tested, where all isolates were susceptible. E-test results revealed high rates of resistance to imipenem, ceftazidime and ciprofloxacin. The majority of isolates (97 %) were multidrug-resistant. OXA-51, OXA-23 and tetB genes were detected in all isolates, but OXA-58, IMP and tetA were not detected. The prevalence of OXA-24, bla(TEM), bla(ADC), bla(VIM) and adeB were 64, 95, 61, 64 and 86 %, respectively. ISAba1 was found to be inserted into the 5' end of OXA-23 in 35 isolates (97 %). Of the AMEs, aadA1 (89 %) was the most prevalent, followed by aphA1 (75 %). The band patterns reproduced by REP-PCR showed that 34 out of 36 isolates belonged to one clone and two singletons were identified. The results confirmed that refractory A. baumannii isolates were widely distributed and warned the hospital infection control team to exert strict measures to control the infection. An urgent surveillance system should be implemented.
Katsiari, Maria; Panagiota, Giakkoupi; Likousi, Sophia; Roussou, Zoi; Polemis, Michalis; Alkiviadis Vatopoulos, C; Evangelia Platsouka, D; Maguina, Asimina
Acquisition of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) strains poses a major threat to critically ill patients. The objectives of this study were to describe the epidemiology of CP-Kp isolates as well as the clinical outcome associated with the corresponding infections and to identify risk factors for mortality of intensive care unit (ICU) patients in a Greek hospital. A prospective, observational study was conducted in a nine-bed general ICU over a 2-year period (April 2010-March 2012). Imipenem-resistant K. pneumoniae isolates recovered from clinical samples of ICU patients were prospectively collected and studied for the presence of carbapenemases. Isolates were submitted to molecular typing using pulsed-field gel electrophoresis (PFGE). In total, 61 CP-Kp isolates (48 KPC-producers and 13 VIM-producers) were recovered from 58 ICU patients. The majority of KPC-producers were classified into a single PFGE type, indicating potent clonal dissemination. Among the 32 infected patients, bacteraemia was diagnosed in 16. Tigecycline+colistin was the most common combination antimicrobial regimen. Infection-attributable mortality was 43.8%. Regarding mortality risk factors, non-survivors were older (P=0.080), all of them presented with septic shock (P=0.010) and they had higher Sepsis-related Organ Failure Assessment (SOFA) scores at infection onset (P=0.004) compared with survivors. Appropriate definitive treatment and combination regimens were not associated with patient survival. In conclusion, CP-Kp infections are associated with limited treatment options and high in-hospital mortality. Effective measures for preventing dissemination of respective isolates in the hospital setting are required. Copyright Â© 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.
Spyropoulou, Aikaterini; Papadimitriou-Olivgeris, Matthaios; Bartzavali, Christina; Vamvakopoulou, Sophia; Marangos, Markos; Spiliopoulou, Iris; Anastassiou, Evangelos D; Christofidou, Myrto
Resistance patterns and carbapenemase gene presence among Klebsiella pneumoniae isolates from the University General Hospital of Patras, Greece during a ten-year period were analysed under a surveillance programme for multi-drug-resistant bacteria. From 2005 to 2014, K. pneumoniae isolates from clinically significant specimens were identified by the Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the agar disc diffusion method and Etest. The strains were tested for the presence of blaVIM, blaIMP, blaKPC, blaNDM and blaOXA-48 genes by PCR. PFGE of chromosomal Xbal DNA digests was performed. A total of 3449 K. pneumoniae isolates were recovered during the last decade. Among them, 1668 (48 %) were carbapenemase-producing: 1333 (80%) K. pneumoniae carbapenemase (KPC)-, 286 (17%) Verona imipenemase (VIM), 45 (3%) KPC- and VIM-, and four New Delhi metallo-beta-lactamase (NDM)-producing. Their resistance rates to gentamicin, colistin and tigecycline were 41%, 23% and 16%, respectively. VIM-producing K. pneumoniae were isolated in 2005 and since 2008 have been endemic. KPC-producing K. pneumoniae (KPC-Kp) isolates were introduced in 2008 and until now represent the predominant carbapenemase-producing K. pneumoniae in our institution. PFGE of 97 KPC-Kp strains identified three types: A, 84 (87%); B, 11 (11%); and E, two (2%). Eleven co-producing KPC and VIM K. pneumoniae isolates belonged to PFGE B. The four NDM-positives were classified to type F. The number of K. pneumoniae bacteraemias increased during the study period, which may be solely attributed to the increase of carbapenemase-producing isolates. The threat of carbapenemase-producing K. pneumoniae emphasizes the urgent need for implementation of infection control measures and budgetary allocations to infection control.
Martha Oliveira Cardoso
Full Text Available Eighty Salmonella Enteritidis strains isolated from broiler carcasses between May 1995 and April 1996 in the State of Rio Grande do Sul, Brazil, were tested for antibiotic susceptibility using the disk diffusion method. Resistance to colistin, novobiocin, erythromycin and tetracycline was observed in 100% of the isolates. The strains showed intermediate resistance at different levels to kanamycin (1.25%, enrofloxacin (3.75%, neomycin (3.75%, fosfomycin (20%, sulphonamides (86.25% and nitrofurantoin (90%. Resistance to ciprofloxacin, norfloxacin, gentamicin, polymyxin B, sulphametrim and sulphazotrim was not found. Since resistance to antibiotics especially those introduced in the last decades, was detected, it is recommended that their use must be based on the results of resistance tests or minimum inhibitory concentration tests.Oitenta amostras de Salmonella Enteritidis isoladas de carcaças de frango no período entre maio de 1995 a abril de 1996 no Estado do Rio Grande do Sul, Brasil foram testados para susceptibilidade antimicrobiana pelo método de antibiograma. O antibiograma das amostras apresentou 100% de resistência a colistina, novobiocina, eritromicina e tetraciclina. Tiveram resistência em diferentes níveis a canamicina (1,25%, enrofloxacina (3,75%, neomicina (3,75%, fosfomicina (20%, sulfonamida (86,25% e nitrofurantoína (90% e por outro lado não apresentaram resistência a ciprofloxacina, norfloxacina, gentamicina, polimixina B, sulfametrim e sulfazotrim. A constatação de resistência a antibióticos, inclusive àqueles introduzidos na última década, enfatiza a necessidade de uso responsável de antibióticos, e com base em antibiograma ou concentração inibitória mínima.
Pontikis, Konstantinos; Karaiskos, Ilias; Bastani, Styliani; Dimopoulos, George; Kalogirou, Michalis; Katsiari, Maria; Oikonomou, Angelos; Poulakou, Garyphallia; Roilides, Emmanuel; Giamarellou, Helen
Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Full Text Available Antibiotic use in food-producing animals has considerable impact on public health, especially with respect to the development and spread of antibiotic resistance. Pigs represent one of the main species in which antibiotics are frequently used for different purposes. Surveillance of antibiotic consumption and dose appropriateness, through novel approaches based on defined daily doses, is strongly needed to assess farms’ antibiotic risk, in terms of spread of antibiotic resistance and possibile presence of residues in meat. In this study, antibiotic consumption was monitored in 14 swine reproduction farms, together with managerial, structural, and health aspects. Most of the controlled farms (65% were classified as at medium antibiotic risk, 21% at high antibiotic risk, and 14% at low antibiotic risk. Critical aspects of antibiotic administration concerned treatments for suckling and weaner piglets, oral antibiotic administration, treatment and diagnosis of gastroenteric infections, and use of critically important antimicrobials for human medicine, especially colistin. These aspects could be considered critical aspects of antibiotic use in from-farrow-to-wean/finish swine farms in the Umbria region and must be controlled to minimize risks. Even though a small number of farms in Umbria region are at high antibiotic risk, the risk of antibiotic resistance should be minimized, and management and biosecurity of the farms should be improved by extending the use of antimicrobial susceptibility tests and optimizing the diagnostic methods for infectious diseases. Furthermore, farmers’ and veterinarians’ knowledge of antibiotic resistance should be improved and the prudent use of antibiotics encouraged to prevent the development and spread of resistant microorganisms.
Van Cuong, Nguyen; Nhung, Nguyen Thi; Nghia, Nguyen Huu; Mai Hoa, Nguyen Thi; Trung, Nguyen Vinh; Thwaites, Guy; Carrique-Mas, Juan
Antimicrobials are extensively used as growth promoters in animal feeds worldwide, but reliable estimates are lacking. We conducted an internet-based survey of commercial chicken and pig feed products officially approved for sale in Vietnam over the period March-June 2015. Information on the antimicrobial contents in feed products, alongside animal production data, was used to estimate in-feed antimicrobial consumption to produce one kilogram of live animal (chicken, pig), as well as to estimate country-wide antimicrobial consumption through animal feeds. A total of 1462 commercial feed formulations were examined. The survey-adjusted estimated antimicrobial contents were 25.7 and 62.3 mg/kg in chicken and pig feeds, respectively. Overall, it was estimated that 77.4 mg [95% CI 48.1-106.8] and 286.6 mg [95% CI 191.6-418.3] of in-feed antimicrobials were used to raise 1 kg of live chicken and pig, respectively. Bacitracin (15.5% feeds), chlortetracycline (11.4%), and enramycin (10.8%) were the most common antimicrobials present in chicken feed formulations, whereas bacitracin (24.8%), chlortetracycline (23.9%), and florfenicol (17.4%) were the most common in pig feed formulations. Overall, 57% of the total quantitative usage consisted of antimicrobials regarded by WHO of importance for human medicine, including amoxicillin, colistin, tetracyclines, neomycin, lincomycin, and bacitracin. These figures confirm a very high magnitude of in-feed consumption of antimicrobials, especially in pig production. Results from this study should encourage further monitoring of antimicrobials used in animal production, and foster discussion about existing policies on inclusion of antimicrobials in animal feed rations.
de Jong, Anno; Thomas, Valérie; Simjee, Shabbir; Godinho, Kevin; Schiessl, Brigitte; Klein, Ulrich; Butty, Pascal; Vallé, Michel; Marion, Hervé; Shryock, Thomas R
To determine the antimicrobial susceptibility of Escherichia coli, Salmonella, Campylobacter and Enterococcus from cattle, pigs and chickens across the European Union (EU) using uniform methodology. Intestinal samples (1624) were taken at slaughter across five EU countries. Bacteria were isolated in national laboratories, whilst MICs were determined in a central laboratory for key antimicrobials used in human medicine. Clinical resistance was based on CLSI breakpoints and decreased susceptibility based on European Food Safety Authority (EFSA)/EUCAST epidemiological cut-off values. Isolation rates were high for E. coli (n=1540), low for Salmonella (n=201) and intermediate for Campylobacter (n=940) and Enterococcus (n=786). For E. coli and Salmonella, clinical resistance to newer compounds (cefepime, cefotaxime and ciprofloxacin) was absent or low, but decreased susceptibility was apparent, particularly in chicken strains. Resistance to older compounds (except gentamicin) was variable and higher. Colistin resistance was absent for E. coli, but apparent for Salmonella. For Campylobacter jejuni, ciprofloxacin resistance was markedly prevalent for chickens, whereas clinical resistance and decreased susceptibility to erythromycin was absent or very low. For Campylobacter coli, resistance was notably higher. None of the Enterococcus faecium strains was resistant to linezolid, but some were resistant to ampicillin or vancomycin. Resistance to quinupristin/dalfopristin was frequent. Resistance patterns varied widely depending on bacterial species, antibiotics, hosts and region. Resistance varied among countries, particularly for older antimicrobials, but clinical resistance to newer antibiotics used to treat foodborne disease in humans was generally very low. In the absence of resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored.
Ansari, M.; Saad, N.
Objective:To differentiate between Ambler class A, B and D of carbapenemase-producing Enterobacteriaceae by using simple phenotypic methods that can be carried out in the laboratory without requiring any specialised techniques. Study Design:Cross-sectional study. Place and Duration of Study:Microbiology Department, Army Medical College, NUST, Islamabad, from November 2015 to November 2016. Methodology: Clinical specimens were subjected to identification of Enterobacteriaceae by colony morphology and API 20 E. Carbapenem resistance was detected by applying meropenem disc (10 mu g) by disc diffusion method according to CLSI (Clinical Laboratory Standard Institute) criteria. Carbapenemase production among Enterobacteriaceaewas detected by Modified Hodge test. Phenotypic methods, Phenylboronic acid (for Class A KPC producing Enterobacteriaceae) and EDTA inhibition tests (for Class B MBL producing Entrobacteriaceae) were applied. Presence of OXA 48 was detected by phenotypic method using imipenem 10 mu g, EDTA and PBA discs. Antibiotic susceptibility was determined by Kirby-Bauer disc diffusion method. Results:Forty-three out of 45 (95.45%) were carbapenemase producers. Thirty-eight out of 43 (88.3%) were KPC producers and 4 out of 43 (11.62%) were MBL producers. All KPC producers were Klebsiella pneumoniae. Among five MBL producers, one each (20%) was Enterobacter cloacae and Escherichia coli and 3 (60%) were Klebsiella pneumoniae. All MBL producers were resistant to aztreonam and amoxicillin/clavulanate. Two of the KPC producing Klebsiella pneumoniaewere pan-drug resistant (resistant to colistin and tigecycline). Two were non-carbapenemase producers. Conclusion:Enterobacteriaceaestrains producing KPC-type carbapenemase were the most prevalent (88.3%) in the studied healthcare setup. (author)
Olusolabomi J Idowu
Full Text Available Background: Extended-spectrum beta-lactamase (ESBL-producing Gram-negative bacteria are emerging and impacting significantly on the management of patients and hospital costs. Besides, they are not being routinely sought after in diagnostic laboratories thus contributing to treatment failure. Materials and Methods: Bacterial isolates from wounds of 45 patients were identified using commercial identification kits and antibiotic susceptibility was evaluated by the Bauer-Kirby method. Screening and phenotypic confirmation of ESBL production were done as prescribed by the Clinical and Laboratory Standards Institute. The conjugation experiment was performed by the mating assay in broth between the ESBL producers and E. coli ATCC 25922 as the recipient. Results: Out of 102 Gram-negative bacteria isolated, 36 were positive for ESBL mainly of the Enterobacteriaceae family (33 and the rest were oxidase-positive bacilli (3. The predominant bacteria were Klebsiella spp. and E. coli. Others were Serratia rubidae, Citrobacter freundii, Morganella morgannii, Proteus spp., Providencia stuartii, and Enterobacter spp. There was a significant association between treatment with third-generation cephalosporins (3GCs and isolation of ESBLs ( p=0.0020 . The ESBL producers were multiply resistant and moderately sensitive to colistin. The conjugation experiment showed that the ESBL gene was transferred horizontally and tetracycline, cotrimoxazole, nitrofurantoin, gentamicin, and aztreonam resistance genes were co-transferred. No mortality was recorded but the mean length of stay in the hospital was 82 days. Conclusion: The development and spread of ESBL among Gram-negative bacteria and possible horizontal transfer calls for concern, especially in view of treatment failure, high treatment cost, and consequent discomfort to patients.
Hussein, K; Bitterman, R; Shofty, B; Paul, M; Neuberger, A
Infections complicating neurosurgery pose unacceptable mortality and morbidity. To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria. However, knowledge of the local epidemiology is necessary to treat PNM. The diagnosis of PNM is difficult because, unlike community-acquired meningitis, symptoms are less specific; patients are ill at baseline and many neurosurgical conditions mimic meningitis and cause cerebrospinal fluid (CSF) abnormalities. Pivotal CSF findings for diagnosis of PNM are the CSF glucose, CSF lactate and Gram stain. CSF leucocyte counts are not specific in PNM. Current diagnostic capabilities leave a non-negligible category of patients with microbiologically negative, uncertain diagnosis of PNM. There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement. Some data point to a potential benefit of IV/IT antibiotic treatment, mainly for PNM caused by carbapenem-resistant Gram-negative bacteria. Carbapenem-colistin combination therapy is suggested for PNM caused by carbapenem-resistant Gram-negative bacteria with a carbapenem MIC ≤8 mg/L. Guiding the optimal management of PNM will necessitate collaborative multicentre efforts and unique study designs. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights
Shofty, B; Neuberger, A; Naffaa, M E; Binawi, T; Babitch, T; Rappaport, Z H; Zaaroor, M; Sviri, G; Paul, M
Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
McDaniel, Cameron; Su, Shengchang; Panmanee, Warunya; Lau, Gee W; Browne, Tristan; Cox, Kevin; Paul, Andrew T; Ko, Seung-Hyun B; Mortensen, Joel E; Lam, Joseph S; Muruve, Daniel A; Hassett, Daniel J
Pseudomonas aeruginosa (PA) is an important airway pathogen of cystic fibrosis and chronic obstructive disease patients. Multiply drug resistant PA is becoming increasing prevalent and new strategies are needed to combat such insidious organisms. We have previously shown that a mucoid, mucA22 mutant PA is exquisitely sensitive to acidified nitrite ([Formula: see text], pH 6.5) at concentrations that are well tolerated in humans. Here, we used a transposon mutagenesis approach to identify PA mutants that are hypersensitive to [Formula: see text]. Among greater than 10,000 mutants screened, we focused on PA4455, in which the transposon was found to disrupt the production of a putative cytoplasmic membrane-spanning ABC transporter permease. The PA4455 mutant was not only highly sensitive to [Formula: see text], but also the membrane perturbing agent, EDTA and the antibiotics doxycycline, tigecycline, colistin, and chloramphenicol, respectively. Treatment of bacteria with [Formula: see text] plus EDTA, however, had the most dramatic and synergistic effect, with virtually all bacteria killed by 10 mM [Formula: see text], and EDTA (1 mM, aerobic, anaerobic). Most importantly, the PA4455 mutant was also sensitive to [Formula: see text] in biofilms. [Formula: see text] sensitivity and an anaerobic growth defect was also noted in two mutants (rmlC and wbpM) that are defective in B-band LPS synthesis, potentially indicating a membrane defect in the PA4455 mutant. Finally, this study describes a gene, PA4455, that when mutated, allows for dramatic sensitivity to the potential therapeutic agent, [Formula: see text] as well as EDTA. Furthermore, the synergy between the two compounds could offer future benefits against antibiotic resistant PA strains.
Zusman, Oren; Avni, Tomer; Leibovici, Leonard; Adler, Amos; Friberg, Lena; Stergiopoulou, Theodouli; Carmeli, Yehuda; Paul, Mical
Our objective was to examine the evidence of in vitro synergy of polymyxin-carbapenem combination therapy against Gram-negative bacteria (GNB). A systematic review and meta-analysis were performed. All studies examining in vitro interactions of antibiotic combinations consisting of any carbapenem with colistin or polymyxin B against any GNB were used. A broad search was conducted with no language, date, or publication status restrictions. Synergy rates, defined as a fractional inhibitory concentration index of ≤0.5 or a >2-log reduction in CFU, were pooled separately for time-kill, checkerboard, and Etest methods in a mixed-effect meta-analysis of rates. We examined whether the synergy rate depended on the testing method, type of antibiotic, bacteria, and resistance to carbapenems. Pooled rates with 95% confidence intervals (CI) are shown. Thirty-nine published studies and 15 conference proceeding were included, reporting on 246 different tests on 1,054 bacterial isolates. In time-kill studies, combination therapy showed synergy rates of 77% (95% CI, 64 to 87%) for Acinetobacter baumannii, 44% (95% CI, 30 to 59%) for Klebsiella pneumoniae, and 50% (95% CI, 30 to 69%) for Pseudomonas aeruginosa, with low antagonism rates for all. Doripenem showed high synergy rates for all three bacteria. For A. baumannii, meropenem was more synergistic than imipenem, whereas for P. aeruginosa the opposite was true. Checkerboard and Etest studies generally reported lower synergy rates than time-kill studies. The use of combination therapy led to less resistance development in vitro. The combination of a carbapenem with a polymyxin against GNB, especially A. baumannii, is supported in vitro by high synergy rates, with low antagonism and less resistance development. These findings should be examined in clinical studies.
Full Text Available Objective: To determine the antimicrobial susceptibility patterns, the frequency of integrons and associated gene cassettes in Acinetobacter baumannii (A. baumannii strains isolated from selected hospital intensive care units. Methods: During a ten-month period, 120 A. baumannii isolates were studied. The resistance rates to different classes of antimicrobial agents were determined. PCR was used to detect different types of integrons and associated gene cassettes. Results: The resistance rates to the majority of antibiotics tested were found to be between 39.3% and 99.1%. No isolate was observed to be resistant to colistin and polymyxin B. The rate of extensive drug-resistance among these clinical isolates was 62.5%. The prevalence of class 1 and 2 integrons was found to be 74.1% and 12.5%, respectively. Seven different gene cassettes (ampC, aacA4-catB8, ISAba1-blaOXA-23-GES-14, aadA2-cm1A6-GES-14-qacF, VIM-25-GES-24-qacF, dfrA5-ISAba1-blaOXA-51-blaOXA-40 and aadA2-GES-11-IMP-1 were observed in Class 1 integron-carrying strains. Three gene cassettes (IMP-4, VIM-2-VEB-aacA4 and dfrA2-sat-2-aadA4 were detected in class 2 integron-bearing A. baumannii strains. Conclusions: A high prevalence of integron was described among multidrug resistant A. baumannii in the hospital. The findings highlighted the need for continuous surveillance in order to prevent dissemination of multidrug resistance among A. baumannii strains in Iran.
Touati, Arabella; Achour, Wafa; Cherif, Ahmed; Hmida, Hayet Ben; Afif, Firas Bou; Jabnoun, Sami; Khrouf, Naima; Hassen, Assia Ben
We describe an outbreak of nosocomial respiratory infection caused by multi-drug resistant Acinetobacter baumannii in a neonatal intensive care unit (NICU) in Tunis and our investigation to determine the source. Between May 2006 and February 2007, 31 infants hospitalized in the NICU of the Centre of Maternity and Neonatology of La Rabta in Tunis developed A. baumannii pneumonia. A case (infected infant) was defined as any patient hospitalized in the NICU during the outbreak period, with clinical signs of pneumonia and isolation of A. baumannii from tracheal aspirate. Ten rectal swabs and 98 environmental specimens were collected for the epidemiological investigation. Thirty-nine A. baumannii isolates were collected: 31 clinical strains from tracheal aspirates (>10(3) colony-forming units [CFU]/mL), 3 environmental strains from incubators, and 5 from rectal swab. For the genotyping method, we used pulsed-field gel electrophoresis using ApaI restriction endonuclease. Thirty-one neonates developed multiple drug-resistant A. baumannii-associated pneumonia with 10 deaths due to A. baumannii infection, 48.4% had very low birth weight (
Full Text Available Abstract Background Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of Klebsiella pneumoniae carbapenemase-producing bacteria is an emerging cause of abdominal infections. Case presentation We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by Klebsiella pneumoniae Sequence Type 258 producing K. pneumoniae carbapenemase 3 (KPC-Kp. In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV- negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE. In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR pathogen. Conclusions Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.
Villegas, Maria Virginia; Pallares, Christian J; Escandón-Vargas, Kevin; Hernández-Gómez, Cristhian; Correa, Adriana; Álvarez, Carlos; Rosso, Fernando; Matta, Lorena; Luna, Carlos; Zurita, Jeannete; Mejía-Villatoro, Carlos; Rodríguez-Noriega, Eduardo; Seas, Carlos; Cortesía, Manuel; Guzmán-Suárez, Alfonso; Guzmán-Blanco, Manuel
Infections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy. Between July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction. Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information. A total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7-9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1-13.7; p mortality. This study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on
Samuelsen, Ørjan; Overballe-Petersen, Søren; Bjørnholt, Jørgen Vildershøj; Brisse, Sylvain; Doumith, Michel; Woodford, Neil; Hopkins, Katie L; Aasnæs, Bettina; Haldorsen, Bjørg; Sundsfjord, Arnfinn
The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS). Patient data were reviewed retrospectively. In total 59 CPE isolates were identified from 53 patients. Urine was the dominant clinical sample source (37%) and only 15% of the isolates were obtained from faecal screening. The majority of cases (62%) were directly associated with travel or hospitalization abroad, but both intra-hospital transmission and one inter-hospital outbreak were observed. The number of CPE cases/year was low (2-14 cases/year), but an increasing trend was observed. Klebsiella spp. (n = 38) and E. coli (n = 14) were the dominant species and blaKPC (n = 20), blaNDM (n = 19), blaOXA-48-like (n = 12) and blaVIM (n = 7) were the dominant carbapenemase gene families. The CPE isolates were genetically diverse except for K. pneumoniae where clonal group 258 associated with blaKPC dominated. All isolates were multidrug-resistant and a significant proportion (21%) were resistant to colistin. Interestingly, all blaOXA-48-like, and a large proportion of blaNDM-positive Klebsiella spp. (89%) and E. coli (83%) isolates were susceptible in vitro to mecillinam. Thus, mecillinam could have a role in the treatment of uncomplicated urinary tract infections caused by OXA-48- or NDM-producing E. coli or K. pneumoniae. In conclusion, the impact of CPE in Norway is still limited and mainly associated with travel abroad, reflected in the diversity of clones and carbapenemase genes.
O'Connor, C; Cormican, M; Boo, T W; McGrath, E; Slevin, B; O'Gorman, A; Commane, M; Mahony, S; O'Donovan, E; Powell, J; Monahan, R; Finnegan, C; Kiernan, M G; Coffey, J C; Power, L; O'Connell, N H; Dunne, C P
Carbapenemase-producing Enterobacteriaceae (CPE) may cause healthcare-associated infections with high mortality rates. New Delhi metallo-β-lactamase-1 (NDM-1) is among the most recently discovered carbapenemases. To report the first outbreak of NDM-1 CPE in Ireland, including microbiological and epidemiological characteristics, and assessing the impact of infection prevention and control measures. This was a retrospective microbiological and epidemiological review. Cases were defined as patients with a CPE-positive culture. Contacts were designated as roommates or ward mates. This outbreak involved 10 patients with a median age of 71 years (range: 45-90), located in three separate but affiliated healthcare facilities. One patient was infected (the index case); the nine others were colonized. Nine NDM-1-producing Klebsiella pneumoniae, an NDM-1-producing Escherichia coli and a K. pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae were detected between week 24, 2014 and week 37, 2014. Pulsed-field gel electrophoresis demonstrated similarity. NDM-1-positive isolates were meropenem resistant with minimum inhibitory concentrations (MICs) ranging from 12 to 32 μg/mL. All were tigecycline susceptible (MICs ≤1 μg/mL). One isolate was colistin resistant (MIC 4.0 μg/mL; mcr-1 gene not detected). In 2015, four further NDM-1 isolates were detected. The successful management of this outbreak was achieved via the prompt implementation of enhanced infection prevention and control practices to prevent transmission. These patients did not have a history of travel outside of Ireland, but several had frequent hospitalizations in Ireland, raising concerns regarding the possibility of increasing but unrecognized prevalence of NDM-1 and potential decline in value of travel history as a marker of colonization risk. Copyright Â© 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Mittal, Gajanand; Gaind, Rajni; Kumar, Deepak; Kaushik, Gaurav; Gupta, Kunj Bihari; Verma, P K; Deb, Monorama
Resistance amongst the commensal flora is a serious threat because a very highly populated ecosystem like the gut, may at a later stage, be a source of extra intestinal infections, resistant strains may spread to other host or transfer genetic resistance element to other members of micro-biota including pathogens. This study was carried out to assess fecal colonization by carbapenemase producing Enterobacteriaceae (CPE) and associated risk factors among 100 patients admitted to intensive care unit (ICU). The phenotypic and molecular characterizations of CPE were also included. Colonization with CPE was observed in 6.6 % (8/122) controls. Among ICU patients, fecal carriage of CPE was significantly higher on day 4 (D4) (22 %) as compared to day 1 (D1) (11 %) (p value 0.002). The carbapenemase genes detected included OXA- 48, 181, KPC and NDM-1 with NDM-1 being the predominant carbapenemase in both ICU D1 and D4. Among the 50 CPE isolates, 8 (16 %) were susceptible to meropenem and imipenem (Minimum inhibitory concentration; MIC ≤ 1 mg/L) and all were susceptible to colistin (MIC range 0.125 - 1 mg/L) and tigecycline (MIC range 0.06- 1.5 mg/L). The risk factors associated with CPE carriage were duration of ICU stay, use of ventilator and aminoglycosides. Prior colonization with CPE could result in their influx and spread in ICU, challenging infection control measures. Exposure to ICU further increases risk of colonization with diverse carbapenemase-producing Enterobacteriaceae. Gut colonization with these strains may be a source of endogenous infection and horizontal transfer of these genes in future.
Full Text Available The prevalence of carbapenemase-producing Enterobacteriaceae (CPE is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS. Patient data were reviewed retrospectively. In total 59 CPE isolates were identified from 53 patients. Urine was the dominant clinical sample source (37% and only 15% of the isolates were obtained from faecal screening. The majority of cases (62% were directly associated with travel or hospitalization abroad, but both intra-hospital transmission and one inter-hospital outbreak were observed. The number of CPE cases/year was low (2-14 cases/year, but an increasing trend was observed. Klebsiella spp. (n = 38 and E. coli (n = 14 were the dominant species and blaKPC (n = 20, blaNDM (n = 19, blaOXA-48-like (n = 12 and blaVIM (n = 7 were the dominant carbapenemase gene families. The CPE isolates were genetically diverse except for K. pneumoniae where clonal group 258 associated with blaKPC dominated. All isolates were multidrug-resistant and a significant proportion (21% were resistant to colistin. Interestingly, all blaOXA-48-like, and a large proportion of blaNDM-positive Klebsiella spp. (89% and E. coli (83% isolates were susceptible in vitro to mecillinam. Thus, mecillinam could have a role in the treatment of uncomplicated urinary tract infections caused by OXA-48- or NDM-producing E. coli or K. pneumoniae. In conclusion, the impact of CPE in Norway is still limited and mainly associated with travel abroad, reflected in the diversity of clones and carbapenemase genes.
Khan, Inam Danish; Basu, Atoshi; Kiran, Sheshadri; Trivedi, Shaleen; Pandit, Priyanka; Chattoraj, Anupam
Device-Associated Healthcare-Associated Infections (DA-HAI), including Ventilator-Associated Pneumonia (VAP), Central-Line-Associated Blood Stream Infection (CLABSI), and Catheter-Related Urinary Tract Infection (CAUTI), are considered as principal contributors to healthcare hazard and threat to patient safety as they can cause prolonged hospital stay, sepsis, and mortality in the ICU. The study intends to characterize DA-HAI in a tertiary care multidisciplinary ICU of a teaching hospital in eastern India. This prospective outcome-surveillance study was conducted among 2157 ICU patients of a 760-bedded teaching hospital in Eastern India. Clinical, laboratory and environmental surveillance, and screening of HCPs were conducted using the US Centers for Disease Control and Prevention (CDC)'s National Healthcare Safety Network (NHSN) definitions and methods. With 8824 patient/bed/ICU days and 14,676 device days, pooled average device utilization ratio was 1.66, total episodes of DA-HAI were 114, and mean monthly rates of DA-HAI, VAP, CLABSI, and CAUTI were 4.75, 2, 1.4, and 1.25/1000 device days. Most common pathogens isolated from DA-HAI patients were Klebsiella pneumoniae (24.6%), Escherichia coli (21.9%), and Pseudomonas aeruginosa (20.2%). All Acinetobacter baumanii , >80% K. pneumoniae and E. coli , and >70% P. aeruginosa were susceptible only to colistin and tigecycline. One P. aeruginosa isolate was panresistant. Mean rates of VAP, CLABSI, and CAUTI were 14.4, 8.1, and 4.5 per 1000 device days, which are comparable with Indian and global ICUs. Patients and HCPs form important reservoirs of infection. Resolute conviction and sustained momentum in Infection Control Initiatives are an essential step toward patient safety.
Candon, Sophie; Perez-Arroyo, Alicia; Marquet, Cindy; Valette, Fabrice; Foray, Anne-Perrine; Pelletier, Benjamin; Milani, Christian; Milani, Cristian; Ventura, Marco; Bach, Jean-François; Chatenoud, Lucienne
Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.
Verdenelli, Maria Cristina; Ghelfi, Francesca; Silvi, Stefania; Orpianesi, Carla; Cecchini, Cinzia; Cresci, Alberto
The possibility of using microbes to maintain health, and to prevent or treat disease is a topic as old as microbiology. The research of novel probiotic strains is important in order to satisfy the increasing request of the market and to obtain functional products in which the probiotic cultures are more active and with better probiotic characteristics than those already present on the market. In this study, the probiotic potential of Lactobacillus strains isolated from Italian elderly human faeces was investigated. The Lactobacillus strains were identified and examined for resistance to gastric acidity and bile toxicity, adhesion to HT-29 cells, antimicrobial activities, antibiotic susceptibility and plasmid profile. Survival of the strains through human intestine was examined in a 3 months human feeding trial. Two strains, Lactobacillus rhamnosus IMC 501 and Lactobacillus paracasei IMC 502, tolerated well low pH and bile acids. In antimicrobial activity assays, both strains showed inhibitory properties towards selected potential harmful microorganisms, particularly against Candida albicans. The two selected strains expressed high in vitro adherence to HT-29 cells increasing this characteristic when they are used in combination and they were resistant to vamcomycin, colistin sulphate, gentamicin, oxolinic acid and kanamycin. Moreover, the two strains could be recovered from stools of volunteers after the feeding trials. Lactobacillus rhamnosus IMC 501 and L. paracasei IMC 502 present favourable strain-specific properties for their utilisation as probiotics in functional foods and the high adhesion ability of the L. rhamnosus IMC 501 and L. paracasei IMC 502 used in combination, confirmed by both in vitro and in vivo study, indicate that the two bacterial strains could be used as health-promoting bacteria.
Pardon, Bart; Catry, Boudewijn; Dewulf, Jeroen; Persoons, Davy; Hostens, Miel; De Bleecker, Koen; Deprez, Piet
To document and quantify drug use in white veal calves, an intensive livestock production system where multidrug resistance is abundantly present. Drug consumption data were prospectively collected on 15 white veal production cohorts (n = 5853 calves) in Belgium (2007-09). Treatment incidences (TIs) based on animal defined daily dose (ADD), prescribed daily dose (PDD) and used daily dose (UDD) were calculated. Risk factors were identified by linear regression. The average TI(ADD) of antimicrobial treatments was 416.8 ADD per 1000 animals at risk. Predominantly, oral group antimicrobial treatments were used (95.8%). Of the oral group antimicrobial treatments, 12% and 88% were used for prophylactic or metaphylactic indications, respectively. The main indication for group and individual drug use was respiratory disease. The most frequently used antimicrobials (group treatments) were oxytetracycline (23.7%), amoxicillin (18.5%), tylosin (17.2%) and colistin (15.2%). Deviations from the leaflet dosage recommendations were frequently encountered, with 43.7% of the group treatments underdosed (often oxytetracycline and tylosin to treat dysbacteriosis). In 33.3% of the oral antimicrobial group treatments a combination of two antimicrobial preparations was used. Smaller integrations used more antimicrobials in group treatments than larger ones (P < 0.05); an integration is defined as a company that combines all steps of the production chain by having its own feed plant and slaughterhouse and by placing its calves in veal herds owned by producers that fatten these calves for this integration on contract. Producers used higher dosages than prescribed by the veterinarian in cohorts with a single caretaker (P < 0.01). The present study provided detailed information on the intensive antimicrobial use in the white veal industry. Reduction can only be achieved by reducing the number of oral group treatments.
Callens, Bénédicte; Persoons, Davy; Maes, Dominiek; Laanen, Maria; Postma, Merel; Boyen, Filip; Haesebrouck, Freddy; Butaye, Patrick; Catry, Boudewijn; Dewulf, Jeroen
The monitoring of antimicrobial use is an essential step to control the selection and spread of antimicrobial resistance. Between January and October 2010 data on prophylactic and metaphylactic antimicrobial use were collected retrospectively on 50 closed or semi-closed pig herds. Ninety-three percent of the group treatments were prophylactic whereas only 7% were methaphylactic. The most frequently used antimicrobials orally applied at group level were colistin (30.7%), amoxicillin (30.0%), trimethoprim-sulfonamides (13.1%), doxycycline (9.9%) and tylosin (8.1%). The most frequently applied injectable antimicrobials were tulathromycin (45.0%), long acting ceftiofur (40.1%) and long acting amoxicillin (8.4%). The treatment incidences (TI) based on the used daily dose pig (UDD(pig) or the actually administered dose per day per kg pig of a drug) for all oral and injectable antimicrobial drugs was on average 200.7 per 1000 pigs at risk per day (min=0, max=699.0), while the TI based on the animal daily dose pig (ADD(pig) or the national defined average maintenance dose per day per kg pig of a drug used for its main indication) was slightly higher (average=235.8, min=0, max=1322.1). This indicates that in reality fewer pigs were treated with the same amount of antimicrobials than theoretically possible. Injectable products were generally overdosed (79.5%), whereas oral treatments were often underdosed (47.3%). In conclusion, this study shows that prophylactic group treatment was applied in 98% of the visited herds and often includes the use of critically important and broad-spectrum antimicrobials. In Belgium, the guidelines for prudent use of antimicrobials are not yet implemented. Copyright © 2012 Elsevier B.V. All rights reserved.
Full Text Available Background: Antibiotics such as fluoroquinolones are used for treating infections caused by Gram-negative bacteria, including Acinetobacter baumannii strains some time have extended-spectrum β-lactamase (ESBL, but ESBL production is rather rare. Resistance to fluoroquinolones antibiotics is mediated by lactamases and other mechanisms of resistance. The aim of the present study was to investigate of the prevalence of ESBL production and clonal relatedness of A. baumannii in Iran. Materials and Methods: A. baumannii isolates identified from patients at hospitals in Kermanshah, Iran, were studied. The double disk method was used for detection of ESBL production. The susceptibility to different antibiotics was determined by the disk diffusion method (CLSI. Clonal relatedness was determined by pulsed-field gel electrophoresis (PFGE and processed by Bionumerics 7.0 software. Statistical analyses were performed using SPSS-16.0. Results: This study showed high prevalence of resistance to ampicillin and cefpodoxim (98.1 and 92.3%. Fifty-two of the 84 isolates were identified as ESBL producers. Only colistin and tigecycline remained active against all isolates tested. The PFGE identified eight distinct pulsotypes: A (N=9, B (N=10, C (N=2, D (N=5, E (N=9, F (N=15, G (N=1 and H (N=1. The PFGE profiles A, B and F were believed to be endemic (specially clone F that was dominant across different wards of the hospitals and appeared to be endemic in the ICU, emergency, pediatric and infection area throughout the years. Conclusion: Early and timely detection of ESBL-producing A. baumannii clones is useful for preventing their spread within the hospital. PFGE analysis is helpful for detection of common strains in different wards and prevention of further spread of these pulsotypes to other hospital environment.
Full Text Available Enterobacter cloacae is a major nosocomial pathogen causing bloodstream infections. We retrospectively conducted a study to assess antimicrobial susceptibility and phylogenetic relationships of E. cloacae bloodstream isolates in two tertiary university-affiliated hospitals in Shanghai, in order to facilitate managements of E. cloacae bloodstream infections and highlight some unknowns for future prevention.Fifty-three non-duplicate E. cloacae bloodstream isolates were consecutively collected from 2013 to 2016. Antimicrobial susceptibility was determined by disk diffusion. PCR was performed to detect extended-spectrum β-lactamase (ESBL, carbapenemase and colistin resistance (MCR-1 gene. Plasmid-mediated AmpC β-lactamase (pAmpC genes were detected using a multiplex PCR assay targeting MIR/ACT gene (closely related to chromosomal EBC family gene and other plasmid-mediated genes, including DHA, MOX, CMY, ACC, and FOX. eBURST was applied to analyze multi-locus sequence typing (MLST.The rates of resistance to all tested antibiotics were 0.05. SHV (6/8, 75.0% and MIR/ACT (15/18, 83.3% predominated in ESBL and pAmpC producers respectively. Moreover, 2 isolates co-carried TEM-1, SHV-12, IMP-26 and DHA-1. MLST analysis distinguished the 53 isolates into 51 STs and only ST414 and ST520 were assigned two isolates of each (2/53.The antimicrobial resistance rates were low among 53 E. cloacae bloodstream isolates in the two hospitals. Multiclonality disclosed no evidence on spread of these isolates in Shanghai. The simultaneous presence of ESBL, carbapenemase and pAmpC detected in 2 isolates was firstly reported in Shanghai, which necessitated active ongoing surveillances and consistent prevention and control of E. cloacae.
Full Text Available Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.
Full Text Available The aim of this survey is to collect data relating to antibacterial drugs used to treat different animals in the veterinary teaching hospital in the province of Kirkuk, which is taking place for the first time at the province level for the purpose of knowing the types of drugs most commonly used and the outcome whether these drugs used are optimal. Data were collected from the veterinary teaching hospital in Kirkuk province for 6 consecutive months and for the period between 1/7/2016 and until 1/1/2017 period included both the summer and autumn and winter seasons. The results show that the most commonly used drugs were Oxytetracycline, Oxytetracycline, Doxycycline-Colistin compound by 26, 57 and 36% in cattle, sheep-goats and Poultry, respectively. While the least commonly used drugs were Tylosin, Gentamicin and Gentamicin-Tylosin compound by 10, 5 and 4% in cattle, sheep-goats and poultry, respectively. Based on the results obtained from this survey, we recommend the use of Penicillin-Streptomycin compound because it has a synergistic effect against most of the resistant bacteria and not to increase usage of Oxytetracycline because of its side effects and lack of effectiveness in recent times due to the abundance of resistant germs. Also, using antibacterial drugs, we would like to note the need for optimal scientific use of these drugs and to give attention to the period in which it takes the medicine to withdraw from the animal body before milking animals or slaughtering it, so that the bacterial resistance does not develop against these drugs in the future.
Domínguez, Isabel; Rosales, Ruth; Cabello, Ángela; Bavestrello, Luis; Labarca, Jaime
Surveillance of antimicrobial consumption is a central part in programs of antibiotic stewardship. However, in Chile there are no national data on antibiotic consumption representing a significant number of hospitals by clinical services. In 2013 a survey was sent to multiple Chilean hospitals to evaluate antimicrobial consumption in medical services (MS), surgery services (SS) and critical care units (ICU). We used the standardized methodology recommended by the WHO, using the number of DDD/100 days beds. In the MS and SS beta-lactam and no beta-lactam antibiotics commonly used were evaluated. In the ICU consumption vancomycin, linezolid, imipenem, merope-nem, colistin and tigecycline was evaluated. Fifteen hospitals reported the density of antimicrobial consumption. Ceftriaxone and cloxacillin were the most commonly used antibiotics in general services (average cloxacillin 4,9 DDD/100 bed days in MS and 8,0 DDD/100 in SS; ceftriaxone 13,5 DDD/100 in MS and 16,7 DDD/100 in SS). In the SS there was also a significant consumption of metronidazole (average 14,5 DDD/100 bed days). In the ICU there was an important variability of consumption of selected antibiotics. This study reports the average and range of antibiotic consumption in MS, SS, and ICU from a significant number of hospitals in the country, during 2013. This information allows hospitals to compare their consumption of antibiotics with a significant sample of Chilean hospitals. Analysis of this information should consider a careful interpretation according to the sample shown here and the reality of each hospital.
Full Text Available Objective: Ventilator-associated pneumonia (VAP is the most common nosocomial infection in the intensive care units (ICUs. It causes prolonged hospital stay and increases mortality. In this study, we aimed to investigate the rate of VAP, causative microorganisms, and their antibiotic susceptibilities in anaesthesiology and reanimation ICU (ARICU. Material and Method: This retrospective study included patients who were admitted to 12-bed ARICU between January 2013 and December 2014. The detection of VAP was done according to Centers for Disease Control and Prevention criteria. The rate of VAP, VAP ratio, and ventilator utilization ratio (VUR were calculated according to guidelines of Turkish National Infection Surveillance Control Group. Endotracheal aspiration samples were collected and cultivated. The identification of the isolates was performed by using VITEK-2 automated system. Antibiotic susceptibilities were determined by the disc diffusion method according to the Clinical and Laboratory Standards Institute criteria. Results: VAP was determined in 16 of 359 patients who required invasive mechanic ventilation for longer than 48 hours and hospitalized in ARICU. VUR was 65%, VAP ratio was 4.5% and the rate of VAP was 3.3 per 1000 ventilator days. Seventeen microorganisms were isolated from endotracheal aspiration samples, including Acinetobacter baumannii (n=6, Pseudomonas aeruginosa (n=4, methicillin-resistant Staphylococcus aureus (n=4, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens. The most sensitive antibiotics for microorganisms are listed as follows; Acinetobacter baumannii: colistin, Pseudomonas aeruginosa: amikacin, carbapenems; Methicillin-resistant Staphylococcus aureus: linezolid, teicoplanin, vancomycin, trimethoprim sulfamethoxazole; Klebsiella and Enterobacteriaceae species: carbapenems, trimethoprim sulfamethoxazole, gentamicin. Conclusion: Intermittent analyses and antibiotic susceptibilities of VAP
Bacterial susceptibility to antibiotics has been shown in vitro to be reduced during spaceflight; however, the underlying mechanisms responsible for this outcome are not fully understood. In particular, it is not yet clear whether this observed response is due to increased drug resistance (a microbial defense response) or decreased drug efficacy (a microgravity biophysical mass transport effect). To gain insight into the differentiation between these two potential causes, an investigation was undertaken onboard the International Space Station (ISS) in 2014 termed Antibiotic Effectiveness in Space-1 (AES-1). For this purpose, E. coli was challenged with two antibiotics, Gentamicin Sulfate and Colistin Sulfate, at concentrations higher than those needed to inhibit growth on Earth. Phenotypic parameters (cell size, cell envelope thickness, population density and lag phase duration) and gene expression were compared between the spaceflight samples and ground controls cultured in varying levels of drug concentration. It was observed that flight samples proliferated in antibiotic concentrations that were inhibitory on Earth, growing on average to a 13-fold greater concentration than matched 1g controls. Furthermore, at the highest drug concentrations in space, E. coli cells were observed to aggregate into visible clusters. In spaceflight, cell size was significantly reduced, translating to a decrease in cell surface area to about one half of the ground controls. Smaller cell surface area can in turn proportionally reduce the rate of antibiotic molecules reaching the cell. Additionally, it was observed that genes --- in some cases more than 2000 --- were overexpressed in space with respect to ground controls. Up-regulated genes include poxB, which helps catabolize glucose into organic acids that alter acidity around and inside the cell, and the gadABC family genes, which confer resistance to extreme acid conditions. The next step is to characterize the mechanisms behind
Full Text Available The objective of our study was to describe the molecular support of carbapenem resistance from randomly selected clinical isolates of multidrug-resistant (MDR Acinetobacter baumannii as a pilot study from the Hamad Medical Corporation (HMC, Qatar. Results of our report will be used to study carbapenemases using molecular techniques in all isolated MDR A. baumannii. Forty-eight MDR A. baumannii were randomly selected from isolates preserved at HMC. Identification of all isolates was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antibiotic resistance was tested phenotypically by Phoenix and confirmed by Etest. The molecular support of carbapenemases (blaOXA-23, blaOXA-24, blaOXA-58, blaNDM was investigated by real-time PCR. The epidemiologic relatedness of the isolates was verified by phylogenetic analysis based on partial sequences of CsuE and blaOXA-51 genes. All 48 isolates were identified as A. baumannii and were confirmed to be resistant to most antibiotics, especially meropenem, imipenems, ciprofloxacin, levofloxacin, amikacin, gentamicin and most of the β-lactams; they were sensitive to colistin. All the isolates were positive for blaOXA-23 and negative for the other tested carbapenemase genes. Clonality analysis demonstrated that different lineages were actually circulating in Qatar; and we suggest that an outbreak occurred in the medical intensive care unit of HMC between 2011 and 2012. Here we report the emergence of MDR A. baumannii producing the carbapenemase OXA-23 in Qatar.
Wu, Congming; Wang, Yingchao; Shi, Xiaomin; Wang, Shuang; Ren, Hongwei; Shen, Zhangqi; Wang, Yang; Lin, Juchun; Wang, Shaolin
Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) strains are emerging around the world as a source of resistance to β-lactam antibiotics such as ampicillin, cefotaxime, and ceftazidime. mcr-1 is a novel plasmid-mediated gene conferring resistance to colistin. The aim of this study was to investigate the prevalence of ESBL-EC mcr-1 of chicken origin in the different provinces of China during 2008-2014. Overall, 341 of 821 isolates were determined to be ESBL-EC strains, and the proportion of ESBL-positive strains almost doubled from 2008 to 2014. The findings of our study revealed regional differences, with significantly more ESBL-EC isolates from stockbreeding in concentrated poultry industry areas in Shandong than from the other four provinces. The ESBL type analysis showed that bla CTX-M was the most prevalent ESBL-encoding gene (92.7%). In total, twelve subtypes of CTX-M genes were detected, among which, bla CTX-M-55 (34.3%) and bla CTX-M-65 (17.9%) were the major identified genotypes. In addition, bla TEM and pAmpC genes were carried by 86.0% and 8.5% of isolates, respectively. In this study, we also observed 44 E. coli isolates with multiple ST types (ST46, ST1286, ST10, ST29, ST101, and ST354) carrying mcr-1, and the majority of mcr-1-carrying plasmids were IncI2. The whole-genome sequencing analysis indicated the co-existence of bla CTX-M and mcr-1 in ESBL-EC of both animal and human origin, and phylogenetic analysis further revealed their close relationship, especially several isolates sharing a small number of SNPs, which suggested the increasing trend of co-existence and transmission of ESBL and mcr-1 in both clinical medicine and veterinary medicine.
Retrospective Analysis of Bacterial Cultures Sampled in German Chicken-Fattening Farms During the Years 2011–2012 Revealed Additional VIM-1 Carbapenemase-Producing Escherichia coli and a Serologically Rough Salmonella enterica Serovar Infantis
Roschanski, Nicole; Fischer, Jennie; Falgenhauer, Linda; Pietsch, Michael; Guenther, Sebastian; Kreienbrock, Lothar; Chakraborty, Trinad; Pfeifer, Yvonne; Guerra, Beatriz; Roesler, Uwe H.
Carbapenems are last-resort antibiotics used in human medicine. The increased detection of carbapenem-resistant Enterobacteriaceae (CRE) is therefore worrying. In 2011 we reported the first livestock-associated VIM-1-producing Salmonella (S.) enterica serovar Infantis (R3) isolate from dust, sampled in a German chicken fattening farm. Due to this observation we retrospectively investigated more than 536 stored bacterial cultures, isolated from 45 chicken fattening farms during the years 2011 and 2012. After a non-selective overnight incubation, the bacteria were transferred to selective media. Escherichia (E.) coli and Salmonella growing on these media were further investigated, including antibiotic susceptibility testing, carbapenemase gene screening and whole genome sequencing (WGS). In total, four CRE were found in three out of 45 investigated farms: Besides R3, one additional Salmonella (G-336-1a) as well as two E. coli isolates (G-336-2, G-268-2). All but G-268-2 harbored the blaVIM-1 gene. Salmonella isolates R3 and G-336-1 were closely related although derived from two different farms. All three blaVIM-1-encoding isolates possessed identical plasmids and the blaVIM-1- containing transposon showed mobility at least in vitro. In isolate G-268-2, the AmpC beta-lactamase gene blaCMY-2 but no known carbapenemase gene was identified. However, a transfer of the phenotypic resistance was possible. Furthermore, G-268-2 contained the mcr-1 gene, combining phenotypical carbapenem- as well as colistin resistance in one isolate. Carbapenem-resistant Enterobacteriaceae have been found in three out of 45 investigated chicken flocks. This finding is alarming and emphasizes the importance of intervention strategies to contain the environmental spread of resistant bacteria in animals and humans. PMID:29636734
Retrospective Analysis of Bacterial Cultures Sampled in German Chicken-Fattening Farms During the Years 2011-2012 Revealed Additional VIM-1 Carbapenemase-Producing Escherichia coli and a Serologically Rough Salmonella enterica Serovar Infantis.
Roschanski, Nicole; Fischer, Jennie; Falgenhauer, Linda; Pietsch, Michael; Guenther, Sebastian; Kreienbrock, Lothar; Chakraborty, Trinad; Pfeifer, Yvonne; Guerra, Beatriz; Roesler, Uwe H
Carbapenems are last-resort antibiotics used in human medicine. The increased detection of carbapenem-resistant Enterobacteriaceae (CRE) is therefore worrying. In 2011 we reported the first livestock-associated VIM-1-producing Salmonella ( S .) enterica serovar Infantis (R3) isolate from dust, sampled in a German chicken fattening farm. Due to this observation we retrospectively investigated more than 536 stored bacterial cultures, isolated from 45 chicken fattening farms during the years 2011 and 2012. After a non-selective overnight incubation, the bacteria were transferred to selective media. Escherichia (E.) coli and Salmonella growing on these media were further investigated, including antibiotic susceptibility testing, carbapenemase gene screening and whole genome sequencing (WGS). In total, four CRE were found in three out of 45 investigated farms: Besides R3, one additional Salmonella (G-336-1a) as well as two E. coli isolates (G-336-2, G-268-2). All but G-268-2 harbored the bla VIM-1 gene. Salmonella isolates R3 and G-336-1 were closely related although derived from two different farms. All three bla VIM-1 -encoding isolates possessed identical plasmids and the bla VIM-1- containing transposon showed mobility at least in vitro . In isolate G-268-2, the AmpC beta-lactamase gene bla CMY-2 but no known carbapenemase gene was identified. However, a transfer of the phenotypic resistance was possible. Furthermore, G-268-2 contained the mcr-1 gene, combining phenotypical carbapenem- as well as colistin resistance in one isolate. Carbapenem-resistant Enterobacteriaceae have been found in three out of 45 investigated chicken flocks. This finding is alarming and emphasizes the importance of intervention strategies to contain the environmental spread of resistant bacteria in animals and humans.
Full Text Available Background: Pseudomonas aeruginosa is a severe challenge for antimicrobial therapy, due to the chromosomal mutations or exhibition of intrinsic resistance to various antimicrobial agents such as most β-lactams. We undertook this study to evaluate the existence of SME, IMP, AIM, and VIM metallo-β-lactamases (MBL encoding genes among P. aeruginosa strains isolated from Intensive Care Unit (ICU patients in Al-Zahra Hospital in Isfahan, Iran. Materials and Methods: In a retrospective cross-sectional study that was conducted between March 2012 and April 2013, a total of 48 strains of P. aeruginosa were collected from clinical specimens of bedridden patients in ICU wards. Susceptibility test was performed by disc diffusion method. All of the meropenem-resistant strains were subjected to modified Hodge test for detection of carbapenemases. Multiplex polymerase chain reaction was performed for detection of blaVIM, blaIMP, blaAIM, and blaSME genes. Results: In disk diffusion method, imipenem and meropenem showed the most and colistin the least resistant antimicrobial agents against P. aeruginosa strains. Of the 48 isolates, 36 (75% were multidrug resistant (MDR. Amplification of β-lactamase genes showed the presence of blaVIM genes in 7 (%14.6 strains and blaIMP genes in 15 (31.3% strains. All of the isolates were negative for blaSME and blaAIM genes. We could not find any statistically significant difference among the presence of this gene and MDR positive, age, or source of the specimen. Conclusion: As patients with infections caused by MBL-producing bacteria are at an intensified risk of treatment failure, fast determination of these organisms is necessary. Our findings may provide useful insights in replace of the appropriate antibiotics and may also prevent MBLs mediated resistance problem.
Full Text Available Background:Pseudomonas aeruginosa is a severe challenge for antimicrobial therapy, because of chromosomal mutations or exhibition of intrinsic resistance to various antimicrobial agents such as most β-lactams. We undertook this study to evaluate the existence of SME, AIM and VIM metallo-beta lactamases encoding genes among P. aeruginosa strains isolated from ICU patients in AL- Zahra Hospital in Esfahan-Iran.Methods : In a retrospective cross sectional study that was conducted between March 2012 toApril 2013, in total 48 strains of P. aeruginosa were collected from clinical specimens of bedridden patients in ICU wards. Susceptibility test was performed by disc diffusion method.All of the meropenem resistant strains were subjected to modified Hodge test (MHT for detection of carbapenemases. Multiplex PCR was performed for detection of VIM, blaAIM,blaSME genes.Results : In disk diffusion method imipenem and meropenem showed the most and colistin the least resistant antimicrobial agents against P. aeruginosa strains. Of the 48 isolates 36, (75% were multidrug resistant. Amplification of β –lactamase genes showed the presence of blaVIM genes in 7 (%14.6 strains. All of the isolates were negative for blaSME and blaAIM genes. We ouldn’t find any statistically significance diffe rence among presence of this gene and MDR positive, age or source of the specimen.Conclusion : As patients with infections caused by MBL-producing bacteria are at an intensified risk of treatment failure, fast determination of these organisms is necessary. Our findings may rovide useful insights in replace of the appropriate antibiotics and may also prevent MBLs mediated resistance problem.
Full Text Available Abstract Introduction Pseudomonas aeruginosa and Acinetobacter spp. are found to be associated with biofilm and metallo-β-lactamase production and are the common causes of serious infections mainly in hospitalized patients. So, the main aims of this study were to determine the rates of biofilm production and metallo beta-lactamase production (MBL among the strains of Pseudomonas aeruginosa and Acinetobacter spp. isolated from hospitalized patients. Methods A total of 85 P. aeruginosa isolates and 50 Acinetobacter spp. isolates isolated from different clinical specimens from patients admitted to Shree Birendra Hospital, Kathmandu, Nepal from July 2013 to May 2014 were included in this study. The bacterial isolates were identified with the help of biochemical tests. Modified Kirby-Bauer disc diffusion technique was used for antimicrobial susceptibility testing. Combined disc diffusion technique was used for the detection of MBL production, while Congo red agar method and tube adherence method were used for detection of biofilm production. Results Around 16.4% of P. aeruginosa isolates and 22% of the strains of Acinetobacter spp. were metallo β-lactamase producers. Out of 85 P. aeruginosa isolates, 23 (27.05% were biofilm producers according to tube adherence test while, only 13 (15.29% were biofilm producers as per Congo red agar method. Similarly, out of 50 Acinetobacter spp. 7 (14% isolates were biofilm producers on the basis of tube adherence test, while only 5 (10% were positive for biofilm production by Congo red agar method. Highest rates of susceptibility of P. aeruginosa as well as Acinetobacter spp. were seen toward colistin. Conclusion In our study, biofilm production and metallo beta-lactamase production were observed among Pseudomonas aeruginosa and Acinetobacter spp. However, no statistically significant association could be established between biofilm production and metallo beta-lactamase production.
Hasan, M J; Shamsuzzaman, S M
The adeB gene in Acinetobacter baumannii regulates the bacterial internal drug efflux pump that plays a significant role in drug resistance. The aim of our study was to determine the occurrence of adeB gene in multidrug resistant and New Delhi metallo-beta-lactamase-1 (NDM- 1) gene in imipenem resistant Acinetobacter baumannii isolated from wound swab samples in a tertiary care hospital of Bangladesh. A total of 345 wound swab samples were tested for bacterial pathogens. Acinetobacter baumannii was identified by culture and biochemical tests. Antimicrobial susceptibility pattern was determined by the disc diffusion method according to CLSI standards. Extended spectrum beta-lactamases were screened using the double disc synergy technique. Gene encoding AdeB efflux pump and NDM-1 were detected by Polymerase Chain Reaction (PCR). A total 22 (6.37%) Acinetobacter baumannii were identified from 345 wound swab samples and 20 (91%) of them were multidrug resistant. High resistance rates to some antibiotics were seen namely, cefotaxime (95%), amoxyclavulanic acid (90%) and ceftriaxone (82%). All the identified Acinetobacter baumannii were sensitive to colistin and 82% to imipenem. Two (9%) ESBL producing Acinetobacter baumannii strains were detected. adeB gene was detected in 16 (80%) out of 20 multidrug resistant Acinetobacter baumannii. 4 (18%) of 22 Acinetobacter baumannii were imipenem resistant. NDM-1 gene was detected in 2 (50%) of the imipenem resistant strains of Acinetobacter baumannii. The results of this study provide insight into the role of adeB gene as a potential regulator of drug resistance in Acinetobacter baumanni in Bangladesh. NDM-1 gene also contributes in developing such resistance for Acinetobacter baumannii.
Full Text Available In the nosocomial setting, antimicrobial-resistant Enterobacteriaceae are a growing challenge, and alarming trends in resistance are currently reported all over the world. Isolates of Enterobacteriaceae producing ampC β-lactamases and extended spectrum β-lactamases are endemic in many hospitals, and are frequently resistant also to other classes of antibiotics, such as fluoroquinolones and aminoglycosides. The risk of infections due to multi-drug resistant strains should be considered also for outpatients who have had recent contact with the health system. Both nosocomial and health-care associated infections should be treated with a combination of antibiotics active against multi-drug resistant Gram negative and methicillin-resistant Staphylococcus aureus. In the absence of effective antimicrobial stewardship programs, this aggressive therapeutic approach might lead to abuse of broad-spectrum antibiotics, with consequent increase in resistances. To contain the possible antibiotic overuse, several decisional strategies, often based on risk-score systems supporting the clinical decisions, have been proposed. In this context of high antibiotic selection pressure, carbapenem-resistant pathogens recently began to spread in many hospitals. Carbapenem-resistant Klebsiella pneumoniae, as well as carbapenem-resistant Acinetobacter baumannii and P. aeruginosa, represent the new major challenges to patient safety. Against these organisms the initial empiric treatment is generally ineffective. The poor clinical outcome associated with carbapenem- resistant K. pneumoniae infections is probably due to the delete in the beginning of an appropriate antibiotic treatment, rather than to the increased virulence of pathogens. Only few therapeutic options are available, including colistin, tigecycline, aminoglycosides and carbapenems in selected cases. Several combinations of these antibiotics have been used, but no ideal regimen has been currently established.
Khorvash, Farzin; Yazdani, Mohammadreza; Shabani, Shiva; Soudi, Aliasghar
Pseudomonas aeruginosa is a severe challenge for antimicrobial therapy, due to the chromosomal mutations or exhibition of intrinsic resistance to various antimicrobial agents such as most β-lactams. We undertook this study to evaluate the existence of SME, IMP, AIM, and VIM metallo-β-lactamases (MBL) encoding genes among P. aeruginosa strains isolated from Intensive Care Unit (ICU) patients in Al-Zahra Hospital in Isfahan, Iran. In a retrospective cross-sectional study that was conducted between March 2012 and April 2013, a total of 48 strains of P. aeruginosa were collected from clinical specimens of bedridden patients in ICU wards. Susceptibility test was performed by disc diffusion method. All of the meropenem-resistant strains were subjected to modified Hodge test for detection of carbapenemases. Multiplex polymerase chain reaction was performed for detection of blaVIM, blaIMP, blaAIM, and blaSME genes. In disk diffusion method, imipenem and meropenem showed the most and colistin the least resistant antimicrobial agents against P. aeruginosa strains. Of the 48 isolates, 36 (75%) were multidrug resistant (MDR). Amplification of β-lactamase genes showed the presence of blaVIM genes in 7 (%14.6) strains and blaIMP genes in 15 (31.3%) strains. All of the isolates were negative for blaSME and blaAIM genes. We could not find any statistically significant difference among the presence of this gene and MDR positive, age, or source of the specimen. As patients with infections caused by MBL-producing bacteria are at an intensified risk of treatment failure, fast determination of these organisms is necessary. Our findings may provide useful insights in replace of the appropriate antibiotics and may also prevent MBLs mediated resistance problem.
Gasparini, Giorgio; De Gori, Marco; Calonego, Giovanni; Della Bora, Tommaso; Caroleo, Benedetto; Galasso, Olimpio
High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing peri-prosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians toward alternative antimicrobial formulations loaded into acrylic bone cement. The aim of this in vitro study was to determine the elution kinetics of 14 different high-dose ALACs. All ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing over time, and elution curves strictly adhered to a nonlinear regression analysis formula. Among aminoglycosides, commonly seen as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, a class of antibiotics that should be considered to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution than teicoplanin. Clindamycin, which can be associated with aminoglycosides to prepare ALACs and represents a useful option against the most common pathogens responsible for PJIs, showed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multidrug-resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics not routinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent a useful option for physicians to eradicate PJIs. In vivo testing should be considered in the future to confirm the results of this study. Copyright 2014, SLACK Incorporated.
Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena; Szulowski, Krzysztof
Monitoring of antimicrobial resistance in commensal Escherichia coli (N = 3430) isolated from slaughtered broilers, laying hens, turkeys, swine, and cattle in Poland has been run between 2009 and 2012. Based on minimal inhibitory concentration (MIC) microbiological resistance to each of 14 tested antimicrobials was found reaching the highest values for tetracycline (43.3%), ampicillin (42.3%), and ciprofloxacin (39.0%) whereas the lowest for colistin (0.9%), cephalosporins (3.6 ÷ 3.8%), and florfenicol (3.8%). The highest prevalence of resistance was noted in broiler and turkey isolates, whereas it was rare in cattle. That finding along with resistance patterns specific to isolation source might reflect antimicrobial consumption, usage preferences or management practices in specific animals. Regression analysis has identified changes in prevalence of microbiological resistance and shifts of MIC values. Critically important fluoroquinolone resistance was worrisome in poultry isolates, but did not change over the study period. The difference (4.7%) between resistance to ciprofloxacin and nalidixic acid indicated the scale of plasmid-mediated quinolone resistance. Cephalosporin resistance were found in less than 3.8% of the isolates but an increasing trends were observed in poultry and MIC shift in the ones from cattle. Gentamycin resistance was also increasing in E. coli of turkey and cattle origin although prevalence of streptomycin resistance in laying hens decreased considerably. Simultaneously, decreasing MIC for phenicols observed in cattle and layers isolates as well as tetracycline values in E. coli from laying hens prove that antimicrobial resistance is multivariable phenomenon not only directly related to antimicrobial usage. Further studies should elucidate the scope of commensal E. coli as reservoirs of resistance genes, their spread and possible threats for human and animal health. PMID:23935596
Full Text Available Antimicrobials have been used in a prophylactic way to decrease the incidence of digestive disorders during the piglet post-weaning period. Nowadays, it is urgent to reduce their consumption in livestock to address the problem of antimicrobial resistance. In this study, the effect of a product on piglet microbiota has been investigated as an alternative to antimicrobials. Three groups of ten post-weaning pigs were sampled at 0, 15 and 30 days one week post-weaning; the control, antibiotic and feed additive group received a standard post-weaning diet without antibiotics or additives, the same diet as the control group but with amoxicillin and colistin sulphate and the same diet as the control group but with a feed additive (Sanacore-EN, Nutriad International N.V., respectively. The total DNA extracted from faeces was used to amplify the 16S RNA gene for massive sequencing under manufacturer's conditions. Sequencing data was quality filtered and analyzed using QIIME software and suitable statistical methods. In general terms, age modifies significantly the microbiota of the piglets. Thus, the oldest the animal, the highest bacterial diversity observed for the control and the feed additive groups. However, this diversity was very similar in the antibiotic group throughout the trial. Interestingly, a clear increase in abundance of Bacillus and Lactobacillus spp was detected within the feed additive group versus the antibiotic and control groups. In conclusion, the feed additive group had a positive effect in the endogenous microbiota of post-weaning pigs increasing both, the diversity of bacterial families and the abundance of lactic acid bacteria during the post-weaning period.
Retrospective Analysis of Bacterial Cultures Sampled in German Chicken-Fattening Farms During the Years 2011–2012 Revealed Additional VIM-1 Carbapenemase-Producing Escherichia coli and a Serologically Rough Salmonella enterica Serovar Infantis
Full Text Available Carbapenems are last-resort antibiotics used in human medicine. The increased detection of carbapenem-resistant Enterobacteriaceae (CRE is therefore worrying. In 2011 we reported the first livestock-associated VIM-1-producing Salmonella (S. enterica serovar Infantis (R3 isolate from dust, sampled in a German chicken fattening farm. Due to this observation we retrospectively investigated more than 536 stored bacterial cultures, isolated from 45 chicken fattening farms during the years 2011 and 2012. After a non-selective overnight incubation, the bacteria were transferred to selective media. Escherichia (E. coli and Salmonella growing on these media were further investigated, including antibiotic susceptibility testing, carbapenemase gene screening and whole genome sequencing (WGS. In total, four CRE were found in three out of 45 investigated farms: Besides R3, one additional Salmonella (G-336-1a as well as two E. coli isolates (G-336-2, G-268-2. All but G-268-2 harbored the blaVIM-1 gene. Salmonella isolates R3 and G-336-1 were closely related although derived from two different farms. All three blaVIM-1-encoding isolates possessed identical plasmids and the blaVIM-1- containing transposon showed mobility at least in vitro. In isolate G-268-2, the AmpC beta-lactamase gene blaCMY-2 but no known carbapenemase gene was identified. However, a transfer of the phenotypic resistance was possible. Furthermore, G-268-2 contained the mcr-1 gene, combining phenotypical carbapenem- as well as colistin resistance in one isolate. Carbapenem-resistant Enterobacteriaceae have been found in three out of 45 investigated chicken flocks. This finding is alarming and emphasizes the importance of intervention strategies to contain the environmental spread of resistant bacteria in animals and humans.
Nicole L Podnecky
Full Text Available Several members of the genus Burkholderia are prominent pathogens. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. Virtually all Burkholderia species are also resistant to polymyxin, prohibiting use of drugs like colistin that are available for treatment of infections caused by most other drug resistant Gram-negative bacteria. Despite clinical significance and antibiotic resistance of Burkholderia species, characterization of efflux pumps lags behind other non-enteric Gram-negative pathogens such as Acinetobacter baumannii and Pseudomonas aeruginosa. Although efflux pumps have been described in several Burkholderia species, they have been best studied in B. cenocepacia and B. pseudomallei. As in other non-enteric Gram-negatives, efflux pumps of the resistance nodulation cell division (RND family are the clinically most significant efflux systems in these two species. Several efflux pumps were described in B. cenocepacia, which when expressed confer resistance to clinically significant antibiotics, including aminoglycosides, chloramphenicol, fluoroquinolones, and tetracyclines. Three RND pumps have been characterized in B. pseudomallei, two of which confer either intrinsic or acquired resistance to aminoglycosides, macrolides, chloramphenicol, fluoroquinolones, tetracyclines, trimethoprim, and in some instances trimethoprim+sulfamethoxazole. Several strains of the host-adapted B. mallei, a clone of B. pseudomallei, lack AmrAB-OprA and are therefore aminoglycoside and macrolide susceptible. B. thailandensis is closely related to B. pseudomallei, but non-pathogenic to humans. Its pump repertoire and ensuing drug resistance profile parallels that of B. pseudomallei. An efflux pump in B. vietnamiensis plays a significant role in acquired aminoglycoside resistance. Summarily, efflux pumps are significant players in Burkholderia drug resistance.
Wang, Mingyu; Shen, Weitao; Yan, Lei; Wang, Xin-Hua; Xu, Hai
Bacteria, antibiotics, and antibiotic resistance determinants are key biological pollutants in aquatic systems, which may lead to bacterial infections or prevent the cure of bacterial infections. In this study, we investigated how the wastewater treatment processes in wastewater treatment plants (WWTPs) affect these pollutants. We found that the addition of oxygen, polyaluminum chloride (PAC), and polyacrylamide (PAM), as well as ultraviolet (UV) disinfection could significantly alter the bacterial communities in the water samples. An overall shift from Gram-negative bacteria to Gram-positive bacteria was observed throughout the wastewater treatment steps, but the overall bacterial biomass was not reduced in the WWTP samples. The antibiotic contents were reduced by the WWTP, but the size of the reduction and the step when antibiotic degradation occurred differed among antibiotics. Ciprofloxacin, sulfamethoxazole and erythromycin could be removed completely by the WWTP, whereas cephalexin could not. The removal of ciprofloxacin, cephalexin, and erythromycin occurred in the anaerobic digester, whereas the removal of sulfamethoxazole occurred after the addition of PAC and PAM, and UV disinfection. Antimicrobial resistance determinants were highly prevalent in all of the samples analyzed, except for those targeting vancomycin and colistin. However, wastewater treatment was ineffective at removing antimicrobial resistance determinants from wastewater. There were strong correlations between intI1, floR, sul1, and ermB, thereby suggesting the importance of integrons for the spread of these antimicrobial resistance genes. In general, this study comprised a stepwise analysis of the impact of WWTPs on three biological pollutants: bacteria, antibiotics, and antimicrobial resistance determinants, where our results suggest that the design of WWTPs needs to be improved to address the threats due to these pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.
Grzybowski, J; Antos-Bielska, M; Ołdak, E; Trafny, E A
Our new collagen dressing has been developed recently. Three types (A, B, and C) of the dressing were prepared in this study. Each type contained bacitracin, neomycin or colistin. The antibiotic was input into: i. collagen sponge (CS)--type A, ii. layer of limited hydrophobicity (LLH)--type B, and iii. into both CS and LLH layers--type C. The final concentration of the antibiotic that resulted from the loading level was 2 mg/cm2 for the dressings of type A and B and 4 mg/cm2 for the dressing of type C. The antibiotics were then extracted from the pieces of dressings for two days through dialysis membrane. Susceptibility of 54 bacterial strains (S. aureus, P. aeruginosa, and Acinetobacter) isolated from burn wounds were tested to the three antibiotics used for preparation of the dressings. The results of the study evidenced that efficiency of released of antibiotics into the extracts depended on the kind of antibiotic and on the type of dressing. The concentration of the antibiotics proved to be much higher than MIC90 values of the bacterial isolates tested in respect to their susceptibility. The dressing containing mixture of the three antibiotics in two layers--CS and LLH is now considered as potentially effective for care of infected wounds. It may be useful for the treatment of infected wounds or for profilaxis of contaminated wounds, ensuring: i. sufficient antimicrobial activity in wound, and ii. optimal wound environment for the presence of collagenic biomaterial on the damaged tissue.
Alonso, C A; Zarazaga, M; Ben Sallem, R; Jouini, A; Ben Slama, K; Torres, C
In the last few years, different surveillances have been published in Africa, especially in northern countries, regarding antimicrobial resistance among husbandry animals. Information is still scarce, but the available data show a worrying picture. Although the highest resistance rates have been described against tetracycline, penicillins and sulphonamides, prevalence of plasmid-mediated quinolone resistance genes and extended spectrum β-lactamase (ESBL) are being increasingly reported. Among ESBLs, the CTX-M-1 group was dominant in most African surveys. Within this group, CTX-M-15 was the main variant both in animals and humans, except in Tunisia where CTX-M-1 was more frequently detected among Escherichia coli from poultry. Certain bla CTX -M-15 -harbouring clones (ST131/B2 or ST405/D) are mainly identified in humans, but they have also been reported in livestock species from Tanzania, Nigeria or Tunisia. Moreover, several reports suggest an inter-host circulation of specific plasmids (e.g. bla CTX -M-1 -carrying IncI1/ST3 in Tunisia, IncY- and Inc-untypeable replicons co-harbouring qnrS1 and bla CTX -M-15 in Tanzania and the worldwide distributed bla CTX -M-15 -carrying IncF-type plasmids). International trade of poultry meat seems to have contributed to the spread of other ESBL variants, such as CTX-M-14, and clones. Furthermore, first descriptions of OXA-48- and OXA-181-producing E. coli have been recently documented in cattle from Egypt, and the emergent plasmid-mediated colistin resistance mcr-1 gene has been also identified in chickens from Algeria, Tunisia and South Africa. These data reflect the urgent need of a larger regulation in the use of veterinary drugs and the implementation of surveillance programmes in order to decelerate the advance of antimicrobial resistance in this continent. © 2017 The Society for Applied Microbiology.
Djordjevic, Z M; Folic, M M; Jankovic, S M
Regular surveillance of antimicrobial resistance is an important component of multifaceted interventions directed at the problem with resistance of bacteria causing healthcare-associated infections (HAIs) in intensive care units (ICUs). Our aim was to analyse antimicrobial consumption and resistance among isolates of Pseudomonas aeruginosa and Acinetobacter spp. causing HAIs, before and after the introduction of mandatory reporting of resistance patterns to prescribers. A retrospective observational study was conducted between January 2011 and December 2015, at an interdisciplinary ICU of the Clinical Centre Kragujevac, Serbia. The intervention consisted of continuous resistance monitoring of all bacterial isolates from ICU patients and biannual reporting of results per isolate to prescribers across the hospital. Both utilization of antibiotics and density of resistant isolates of P. aeruginosa and Acinetobacter spp. were followed within the ICU. Resistance densities of P. aeruginosa to all tested antimicrobials were lower in 2015, in comparison with 2011. Although isolates of Acinetobacter spp. had lower resistance density in 2015 than in 2011 to the majority of investigated antibiotics, a statistically significant decrease was noted only for piperacillin/tazobactam. Statistically significant decreasing trends of consumption were recorded for third-generation cephalosporins, aminoglycosides and fluoroquinolones, whereas for the piperacillin/tazobactam, ampicillin/sulbactam and carbapenems, utilization trends were decreasing, but without statistical significance. In the same period, increasing trends of consumption were observed for tigecycline and colistin. Regular monitoring of resistance of bacterial isolates in ICUs and reporting of summary results to prescribers may lead to a significant decrease in utilization of some antibiotics and slow restoration of P. aeruginosa and Acinetobacter spp. susceptibility. © 2017 John Wiley & Sons Ltd.
Wood, G Christopher; Swanson, Joseph M
A significant percentage of patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have poor outcomes with intravenous antibiotics. It is not clear if adding aerosolized antibiotics improves treatment. This review is an update on using aerosolized antibiotics for treating HAP/VAP in adults. PubMed search using the terms "aerosolized antibiotics pneumonia," "nebulized antibiotics pneumonia," and "inhaled antibiotics pneumonia." Reference lists from identified articles were also searched. Clinical studies of aerosolized antibiotics for treating HAP/VAP in adults from July 2010 to March 2017. This article updates a previous review on this topic written in mid-2010. The size and quality of studies have improved dramatically in the recent time period compared to previous studies. However, there still are not large randomized controlled trials available. Colistin and aminoglycosides were the most commonly studied agents, and the most common pathogens were Pseudomonas and Acinetobacter. The clinical efficacy of adding aerosolized antibiotics was mixed. Approximately half of the studies showed better outcomes, and none showed worse outcomes. Aerosolized antibiotics appear to be relatively safe, though pulmonary adverse events can occur. Attention to proper administration technique in mechanically ventilated patients is required, including the use of vibrating plate nebulizers. Adding aerosolized antibiotics to intravenous antibiotics may improve the outcomes of adult patients with HAP/VAP in some settings. It seems reasonable to add aerosolized antibiotics in patients with multidrug-resistant organisms or who appear to be failing therapy. Clinicians should pay attention to potential adverse events and proper administration technique.
Saseedharan, Sanjith; Sahu, Manisa; Pathrose, Edwin Joseph; Shivdas, Sarita
Carbapenem-resistant Enterobacteriaceae (CRE) are drug-resistant Gram-negative bacteria that are present in the community as well as in hospitals. Their infection and colonisation puts critically ill patients at high risk due to the drug-resistant nature of the strains and possible spreading of these organisms, even in a hospital environment. To examine the presence and types of Enterobacteriaceae species in patients admitted directly from the community. The present study was a one-month pilot conducted in the ICU of a tertiary care hospital in Mumbai, India in 2015. Faecal samples of patients admitted from the community directly to the ICU were analysed using tests like MHT (Modified Hodge) and EDTA for the presence of IMP (action on Imipenem) and KPC ( Klebsiella Test Pneumoniae Carbapenemase) producing strains of Enterobacteriaceae . Polymerase Chain Reaction (PCR) was performed to look for VIM , IMP , NDM 1, OXA , and KPC genes. Antibiotic Sensitivity Test was carried out as per CLSI guidelines. The results showed an alarming level of faecal carriage rates in adult ICU patients. Klebsiella pneumonia was the most common carbapenem-resistant isolate, closely followed by Escherichia coli . PCR results revealed nine strains were positive for bla (KPC) gene, from which 7 were Klebsiella pneumoniae and one each of Escherichia coli and Klebsiella oxytoca was observed. Antibiotic Sensitivity Test results showed that the isolates had maximum sensitivity to Colistin (100%) and Tigecycline (95%). These levels indicate that in the absence of CRE screenings, proper isolation of carrier patients is not possible, leading to possible spreading of these resistant bacteria strains in ICUs. A longer period of study is required to obtain more substantial data to validate the results of this pilot.
Bassetti, Matteo; Repetto, Ernestina
Among Gram negative bacteria, Pseudomonas aeruginosa, the extended spectrum beta-lactamases (ESBL)-producing strains, Acinetobacter spp, in particular the multiresistant Acinetobacter baumannii, and Stenotrophomonas maltophilia are the most implicated micrororganisms in the ever more increasing problem of bacterial resistance. Possible solutions have to be searched, on one hand, in the use of new drugs but, on the other hand, in the re-evaluation of those already available drugs, possibly considering a new role for old drugs such as colistine and fosfomycin. Concerning ESBL-producing strains, the most recent data provided by EARSS report, in Italy, an incidence rate of 10-25 percent. The insurgence of an infection sustained by an ESBL+ve strain is strictly related to some well known risk factors, like the hospital stay itself, the disease severity, the length of stay in ICU, intubation and mechanical ventilation, catheterization, urinary or artery, and the past exposure to antibiotics. The raise in ESBL producing strains is closely related to the increasing use of cephalosporins. In the setting of a Gram negative infection, the combination therapy guarantees a higher coverage by reducing insurgence of possible resistance mechanisms, possibly resulting synergistic, and allowing a de-escalation therapy, although to this latter other problems, such as tolerability, costs and compliance, can be related. Another basic aspect to take into account of, in order to achieve the maximal efficacy of the antibiotic treatment, is the right dosage. In the idea to look for the best approach for the antibiotic treatment of a severe infection in a hospital setting, when a Gram negative aetiology is implicated, it can be possibly presumed that the right way consists in avoiding inappropriate antibiotic therapies, making therapeutic choices based on guidelines resulted from local epidemiological data, initiating the therapy promptly, avoiding excessive use of antibiotics, possibly
Full Text Available Clinical and paraclinical investigations (morpho-pathologic, bacterioscopic, bacteriologic and sensitiveness test toantibodies done on 20 fish (rainbow trout, dead or in agony state, taken from a furunculosis pesthole in Salmonidaeand proceeded from an intensive exploitation unit of trout, in Cluj county, put in evidence the following aspects :Toclinical exam, in breeding basins, it appears individuals (5 % which have presented locomotor troubles, listless anduntidy swimming in water surface, lateral swimming anorexia, and on tegument it is observed diffuse hemorrhagiczones, lost of fish scale and necrosis of fins. It appears also secondary infections with fungi of Saprolegnia genusunder the form of a white- dirty, downy film. From the 20 trut corpses were isolated 2 bacterial strains, from anteriorkidney and from raclage in fin basis, with congestive lesions. Bacteria isolated are developing only after anincubation at 20 – 250 C and does not grow up to 370 C, and to microscopic exam directly from sauce, the mobility isabsent Classic biochemical tests put in evidence the following positive biochemic properties: cataloze, oxidaze,indolal and the presence of hemolytic activity. Biochemical properties testing on API20E gallery also puts inevidence properties as : positive gelatinousis and sucraze fermentation. Based on bacterial strains developmentisolated only to 20 - 250C and the above mentioned biochemic properties, respectively the absence of pigment,bacterial strains isolated are appointed in Aeromonas genus, Aeromonas salmonicida species, achromogenessubspecies. By sensitiveness test in different medicine substances, using antibiogram technique, bacterial strainsisolated from pesthole are sensitive in a decreasing order to: nalidixic acid, oxitetracycline, florfenicol andeurofloxacin and resistant to ampicyline, amoxiclav and colistin.
Full Text Available Monitoring of antimicrobial resistance in commensal Escherichia coli (N = 3430 isolated from slaughtered broilers, laying hens, turkeys, swine, and cattle in Poland has been run between 2009 and 2012. Based on minimal inhibitory concentration (MIC microbiological resistance to each of 14 tested antimicrobials was found reaching the highest values for tetracycline (43.3%, ampicillin (42.3%, and ciprofloxacin (39.0% whereas the lowest for colistin (0.9%, cephalosporins (3.6 ÷ 3.8%, and florfenicol (3.8%. The highest prevalence of resistance was noted in broiler and turkey isolates, whereas it was rare in cattle. That finding along with resistance patterns specific to isolation source might reflect antimicrobial consumption, usage preferences or management practices in specific animals. Regression analysis has identified changes in prevalence of microbiological resistance and shifts of MIC values. Critically important fluoroquinolone resistance was worrisome in poultry isolates, but did not change over the study period. The difference (4.7% between resistance to ciprofloxacin and nalidixic acid indicated the scale of plasmid-mediated quinolone resistance. Cephalosporin resistance were found in less than 3.8% of the isolates but an increasing trends were observed in poultry and MIC shift in the ones from cattle. Gentamycin resistance was also increasing in E. coli of turkey and cattle origin although prevalence of streptomycin resistance in laying hens decreased considerably. Simultaneously, decreasing MIC for phenicols observed in cattle and layers isolates as well as tetracycline values in E. coli from laying hens prove that antimicrobial resistance is multivariable phenomenon not only directly related to antimicrobial usage. Further studies should elucidate the scope of commensal E. coli as reservoirs of resistance genes, their spread and possible threats for human and animal health.
Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny
To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to
Appropriateness of antibiotic prescription for targeted therapy of infections caused by multidrug-resistant bacteria: assessment of the most common improper uses in a tertiary hospital in southern Italy.
Viceconte, Giulio; Maraolo, Alberto Enrico; Iula, Vita Dora; Catania, Maria Rosaria; Tosone, Grazia; Orlando, Raffaele
A huge proportion of antibiotic therapies for infections caused by multidrug-resistant bacteria (MDR) are inappropriate. In this study, we described the most common causes of inappropriateness of definitive antibiotic regimes in a large university hospital in southern Italy and we evaluated the impact on microbial eradication, length of stay, 30-day readmission and mortality. We retrospectively assessed 45 patients who received a definitive antibiotic therapy after isolation of multidrug-resistant Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. strains between 2014 and 2015. From the literature, we set a series of criteria to retrospectively determine the appropriateness of the therapy. In all, 61% of the prescribed antibiotic regimes were found to be inappropriate, especially due to incorrect drug dosage. It emerged that meropenem was the antibiotic most frequently inappropriately used. In 46% of infections caused by MDR but not extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenems were inappropriately administered. Microbial eradication was achieved in 87% of the appropriate therapy group compared to 31% of the inappropriate therapy group (chi-square=6.750, p<0.027). No statistically significant association was found between inappropriate therapy and the length of stay (chi-square=3.084, p=0.101) and 30-day readmission (p=0.103). Definitive antibiotic therapy in infections caused by multidrug-resistant bacteria in a large university hospital is often inappropriate, especially due to the drug dosing regimen, particularly in the case of meropenem and colistin. This inappropriateness has a significant impact on post-treatment microbial eradication in specimens collected after antibiotic therapy.
Fleming, Erin; Heil, Emily L; Hynicka, Lauren M
To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in