Gram negative wound infection in hospitalised adult burn patients--systematic review and metanalysis-.

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Ernest A Azzopardi

Full Text Available BACKGROUND: Gram negative infection is a major determinant of morbidity and survival. Traditional teaching suggests that burn wound infections in different centres are caused by differing sets of causative organisms. This study established whether Gram-negative burn wound isolates associated to clinical wound infection differ between burn centres. METHODS: Studies investigating adult hospitalised patients (2000-2010 were critically appraised and qualified to a levels of evidence hierarchy. The contribution of bacterial pathogen type, and burn centre to the variance in standardised incidence of Gram-negative burn wound infection was analysed using two-way analysis of variance. PRIMARY FINDINGS: Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumanni, Enterobacter spp., Proteus spp. and Escherichia coli emerged as the commonest Gram-negative burn wound pathogens. Individual pathogens' incidence did not differ significantly between burn centres (F (4, 20 = 1.1, p = 0.3797; r2 = 9.84. INTERPRETATION: Gram-negative infections predominate in burn surgery. This study is the first to establish that burn wound infections do not differ significantly between burn centres. It is the first study to report the pathogens responsible for the majority of Gram-negative infections in these patients. Whilst burn wound infection is not exclusive to these bacteria, it is hoped that reporting the presence of this group of common Gram-negative "target organisms" facilitate clinical practice and target research towards a defined clinical demand.

Black-pigmented gram-negative anaerobes in endodontic infections.

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Haapasalo, M

1993-03-01

Necrotic dental root canal infections are polymicrobial infections dominated by anaerobic bacteria. The number of different species in one canal is usually low, approx. 4-7 species. The species isolated most frequently belong to the genera Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Eubacterium and Streptococcus. The frequency of isolation of black-pigmented Gram-negative anaerobes in endodontic infections varies from 25% to > 50%. Pr. intermedia is the most commonly found pigmented species, followed by Pr. denticola and two Porphyromonas species, P. gingivalis and P. endodontalis. Several studies have shown that P. gingivalis and P. endodontalis are closely related to the presence of acute symptoms in endodontic infections, whereas other black-pigmented Gram-negative anaerobes are not. However, several other species may also be involved in acute infections. Moreover, Porphyromonas species have occasionally been isolated from cases with no symptoms. Although Porphyromonas spp. are clearly related to symptoms at the beginning of therapy, they are not important for the prognosis of the treatment.

In vitro activity of aminoglycosides against clinical isolates of Acinetobacter baumannii complex and other nonfermentative Gram-negative bacilli causing healthcare-associated bloodstream infections in Taiwan.

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Liu, Jyh-You; Wang, Fu-Der; Ho, Mao-Wang; Lee, Chen-Hsiang; Liu, Jien-Wei; Wang, Jann-Tay; Sheng, Wang-Huei; Hseuh, Po-Ren; Chang, Shan-Chwen

2016-12-01

Aminoglycosides possess in vitro activity against aerobic and facultative Gram-negative bacilli. However, nationwide surveillance on susceptibility data of Acinetobacter baumannii complex and Pseudomonas aeruginosa to aminoglycosides was limited, and aminoglycoside resistance has emerged in the past decade. We study the in vitro susceptibility of A. baumannii complex and other nonfermentative Gram-negative bacilli (NFGNB) to aminoglycosides. A total of 378 NFGNB blood isolates causing healthcare-associated bloodstream infections during 2008 and 2013 at four medical centers in Taiwan were tested for their susceptibilities to four aminoglycosides using the agar dilution method (gentamicin, amikacin, tobramycin, and isepamicin) and disc diffusion method (isepamicin). A. baumannii was highly resistant to all four aminoglycosides (range of susceptibility, 0-4%), whereas >80% of Acinetobacter nosocomialis and Acinetobacter pittii blood isolates were susceptible to amikacin (susceptibility: 96% and 91%, respectively), tobramycin (susceptibility: 92% and 80%, respectively), and isepamicin (susceptibility: 96% and 80%, respectively). All aminoglycosides except gentamicin possessed good in vitro activity (>94%) against P. aeruginosa. Amikacin has the best in vitro activity against P. aeruginosa (susceptibility, 98%), followed by A. nosocomialis (96%), and A. pittii (91%), whereas tobramycin and isepamicin were less potent against A. pittii (both 80%). Aminoglycoside resistances were prevalent in Stenotrophomonas maltophilia and Burkholderia cepacia complex blood isolates in Taiwan. Genospecies among the A. baumannii complex had heterogeneous susceptibility profiles to aminoglycosides. Aminoglycosides, except gentamicin, remained good in vitro antimicrobial activity against P. aeruginosa. Further in vivo clinical data and continuous resistance monitoring are warranted for clinical practice guidance. Copyright © 2015. Published by Elsevier B.V.

Risk factors for multidrug-resistant Gram-negative infection in burn patients.

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Vickers, Mark L; Dulhunty, Joel M; Ballard, Emma; Chapman, Paul; Muller, Michael; Roberts, Jason A; Cotta, Menino O

2018-05-01

Infection with multidrug-resistant (MDR) Gram-negative organisms leads to poorer outcomes in the critically ill burn patient. The aim of this study was to identify the risk factors for MDR Gram-negative pathogen infection in critically ill burn patients admitted to a major tertiary referral intensive care unit (ICU) in Australia. A retrospective case-control study of all adult burn patients admitted over a 7-year period was conducted. Twenty-one cases that cultured an MDR Gram-negative organism were matched with 21 controls of similar age, gender, burn size and ICU stay. Multivariable conditional logistic regression was used to individually assess risk factors after adjusting for Acute Burn Severity Index. Adjusted odds ratios (ORs) were reported. P-values negative infection included superficial partial thickness burn size (OR: 1.08; 95% confidence interval (CI): 1.01-1.16; P-value: 0.034), prior meropenem exposure (OR: 10.39; 95% CI: 0.96-112.00; P-value: 0.054), Gram-negative colonization on admission (OR: 9.23; 95% CI: 0.65-130.15; P-value: 0.10) and escharotomy (OR: 2.66; 95% CI: 0.52-13.65; P-value: 0.24). For cases, mean age was 41 (SD: 13) years, mean total body surface area burned was 47% (SD: 18) and mean days in ICU until MDR specimen collection was 17 (SD: 10) days. Prior meropenem exposure, Gram-negative colonization on admission, escharotomy and superficial partial thickness burn size may be potentially important factors for increasing the risk of MDR Gram-negative infection in the critically ill burn patient. © 2017 Royal Australasian College of Surgeons.

[Influence of serious infections due to Gram-negative bacteria on the hospital economy].

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Martínez, B; Gómez, J; Gómez Vargas, J; Guerra, B; Ruiz Gómez, J; Simarro, E; Baños, V; Canteras, M; Valdes, M

2000-12-01

Nosocomial infections due to Gram-negative bacteria are very important since they are associated with high morbidity and high hospital costs. A prospective study of 250 inpatients was carried out, 200 of whom had Gram-negative bacterial infections. Patients were divided into groups of 50 according to the localization of the infection (urinary, surgical wound, respiratory tract and bacteremia), with a control group of 50 patients with similar characteristics but no infection. We calculated the cost for the different groups by multiplying the average length of hospital stay in days by the daily cost of the stay. Significant differences were observed in the average length of stay per patient according to the type of infection and how it was acquired. In terms of cost, nosocomial infection due to Gram-negative bacteria was 1,049,139 pesetas more expensive than community-acquired infection. The cost of the stay for patients with postsurgical infection due to Gram-negative bacteria was 1,108, 252 pesetas more expensive than for the group of control patients. Nosocomial infection due to Gram-negative bacteria is associated with a prolongation in hospital stay of 9 to 28 days, which is the factor that most reflects the cost that can be attributed to nosocomial infection. Consensual and protocolized measures which allow for better clinical management need to be developed.

Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria.

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Yan, Sheng Tao; Sun, Li Chao; Jia, Hong Bing; Gao, Wen; Yang, Jian Ping; Zhang, Guo Qiang

2017-04-01

The aim of this study was to evaluate procalcitonin (PCT) diagnostic accuracy in discriminating gram-negative (GN) from gram-positive (GP) bloodstream infections and determining the relationship between PCT levels, infection sites, and pathogen types. Clinical and laboratory data were collected from patients with blood culture (BC)-positive sepsis between January 2014 and December 2015. PCT levels at different infection sites were compared, as was the presence of GN and GP bloodstream infection. A receiver operating characteristic (ROC) curve was generated to assess diagnostic accuracy. Of the 486 monomicrobial BCs, 254 (52.26%) were positive for GN bacteria (GNB), and 202 (42.18%) for GP bacteria (GPB). Median PCT levels were higher in BCs positive for GN (2.42ng/ml, IQR: 0.38-15.52) than in those positive for GPB (0.49ng/ml, IQR: 0.13-5.89) (PAcinetobacter baumanni/Burkholderia cepacia, Klebsiella pneumonia and Acinetobacter baumanni. PCT levels caused by GPB differed between Staphylococcus epidermidis/Staphylococcus aureus and Staphylococcus hominis/Staphylococcus haemolyticus, Enterococcus faecium and Enterococcus faecalis/S.hominis/S. haemolyticus. Among patients with known infection sites, there were statistical differences in PCT levels between abdominal infection and pneumonia/infective endocarditis, urinary tract infection and pneumonia/catheter-related infection/infective endocarditis. PCT can distinguish between GNB and GPB infection, as well as between different bacterial species and infection sites. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of blood culture systems in the evaluation of epidemiological features of coagulase-negative staphylococcal bloodstream infection in critically ill patients.

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Oud, L; Krimerman, S; Salam, N; Srugo, I

1999-12-01

The impact of blood culture systems on the detection of coagulase-negative staphylococcal bloodstream infections in critically ill patients prior to and following the introduction of the Bactec 9240 blood culture system (Becton Dickinson Diagnostic Instrument Systems, USA), which replaced the Bactec NR 730 (Becton Dickinson Diagnostic Instrument Systems), was investigated over a 3-year period. Following the introduction of the new culture system, the incidence of bloodstream infections doubled (P<0.001). Patient demographics, severity of illness, and mortality remained unchanged, while the annual standardized mortality ratio decreased significantly. These data suggest that blood culture systems may have a major impact on the perceived incidence of coagulase-negative staphylococcal bloodstream infections in this population.

Nosocomial Bloodstream Infections in Brazilian Pediatric Patients: Microbiology, Epidemiology, and Clinical Features

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Pereira, Carlos Alberto Pires; Marra, Alexandre R.; Camargo, Luis Fernando Aranha; Pignatari, Antônio Carlos Campos; Sukiennik, Teresa; Behar, Paulo Renato Petersen; Medeiros, Eduardo Alexandrino Servolo; Ribeiro, Julival; Girão, Evelyne; Correa, Luci; Guerra, Carla; Carneiro, Irna; Brites, Carlos; Reis, Marise; de Souza, Marta Antunes; Tranchesi, Regina; Barata, Cristina U.; Edmond, Michael B.

2013-01-01

Background Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients. Methods We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project). Results In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem. Conclusions In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients. PMID:23861860

Inhaled Antibiotics for Gram-Negative Respiratory Infections

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Fraidenburg, Dustin R.; Scardina, Tonya

2016-01-01

SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

STUDY ON SURGICAL SITE INFECTIONS CAUSED BY ESBL PRODUCING GRAM NEGATIVE BACTERIA

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Rambabu

2015-09-01

Full Text Available Surgical site infections have been a major problem, because of the emergence of drug resistant bacteria, in particular B - lactamase producing bacteria. Extended spectrum beta lactamase producing gram negative organisms pose a great challenge in treatment o f SSI present study is aimed at determining multiple drug resistance in gram negative bacteria & to find out ESBL producers, in correlation with treatment outcome. A total of 120 wound infected cases were studied. Staphylococcus aureus was predominant bact erium - 20.Among gram negative bacteria, Pseudomonas species is predominant (14 followed by Escherichia coli (13 , Klebsiella species (12 , Proteus (9 Citrobacter (4 Providencia (2 & Acinetobacter species (2 . Out of 56 gramnegative bacteria isolated, 20 were i dentified as ESBL producers, which was statistically significant. Delay in wound healing correlated with infection by ESBL producers, which alarms the need of abstinence from antibiotic abuse

Neither Single nor a Combination of Routine Laboratory Parameters can Discriminate between Gram-positive and Gram-negative Bacteremia

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Ratzinger, Franz; Dedeyan, Michel; Rammerstorfer, Matthias; Perkmann, Thomas; Burgmann, Heinz; Makristathis, Athanasios; Dorffner, Georg; Loetsch, Felix; Blacky, Alexander; Ramharter, Michael

2015-01-01

Adequate early empiric antibiotic therapy is pivotal for the outcome of patients with bloodstream infections. In clinical practice the use of surrogate laboratory parameters is frequently proposed to predict underlying bacterial pathogens; however there is no clear evidence for this assumption. In this study, we investigated the discriminatory capacity of predictive models consisting of routinely available laboratory parameters to predict the presence of Gram-positive or Gram-negative bacteremia. Major machine learning algorithms were screened for their capacity to maximize the area under the receiver operating characteristic curve (ROC-AUC) for discriminating between Gram-positive and Gram-negative cases. Data from 23,765 patients with clinically suspected bacteremia were screened and 1,180 bacteremic patients were included in the study. A relative predominance of Gram-negative bacteremia (54.0%), which was more pronounced in females (59.1%), was observed. The final model achieved 0.675 ROC-AUC resulting in 44.57% sensitivity and 79.75% specificity. Various parameters presented a significant difference between both genders. In gender-specific models, the discriminatory potency was slightly improved. The results of this study do not support the use of surrogate laboratory parameters for predicting classes of causative pathogens. In this patient cohort, gender-specific differences in various laboratory parameters were observed, indicating differences in the host response between genders. PMID:26522966

Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

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Ruolin Li

2016-05-01

Full Text Available OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1 patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2 patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman’s correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01. The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01 at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%; a specificity of 73.7% (56.9-86.6%; positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the

[Diagnostic and therapeutic management of Gram-negative infections].

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Bassetti, Matteo; Repetto, Ernestina

2008-04-01

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

Performance of Gram staining on blood cultures flagged negative by an automated blood culture system.

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Peretz, A; Isakovich, N; Pastukh, N; Koifman, A; Glyatman, T; Brodsky, D

2015-08-01

Blood is one of the most important specimens sent to a microbiology laboratory for culture. Most blood cultures are incubated for 5-7 days, except in cases where there is a suspicion of infection caused by microorganisms that proliferate slowly, or infections expressed by a small number of bacteria in the bloodstream. Therefore, at the end of incubation, misidentification of positive cultures and false-negative results are a real possibility. The aim of this work was to perform a confirmation by Gram staining of the lack of any microorganisms in blood cultures that were identified as negative by the BACTEC™ FX system at the end of incubation. All bottles defined as negative by the BACTEC FX system were Gram-stained using an automatic device and inoculated on solid growth media. In our work, 15 cultures that were defined as negative by the BACTEC FX system at the end of the incubation were found to contain microorganisms when Gram-stained. The main characteristic of most bacteria and fungi growing in the culture bottles that were defined as negative was slow growth. This finding raises a problematic issue concerning the need to perform Gram staining of all blood cultures, which could overload the routine laboratory work, especially laboratories serving large medical centers and receiving a large number of blood cultures.

Combating multidrug-resistant Gram-negative bacterial infections.

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Xu, Ze-Qi; Flavin, Michael T; Flavin, John

2014-02-01

Multidrug-resistant (MDR) bacterial infections, especially those caused by Gram-negative pathogens, have emerged as one of the world's greatest health threats. The development of novel antibiotics to treat MDR Gram-negative bacteria has, however, stagnated over the last half century. This review provides an overview of recent R&D activities in the search for novel antibiotics against MDR Gram-negatives. It provides emphasis in three key areas. First, the article looks at new analogs of existing antibiotic molecules such as β-lactams, tetracyclines, and aminoglycoside as well as agents against novel bacterial targets such as aminoacyl-tRNA synthetase and peptide deformylase. Second, it also examines alternative strategies to conventional approaches including cationic antimicrobial peptides, siderophores, efflux pump inhibitors, therapeutic antibodies, and renewed interest in abandoned treatments or those with limited indications. Third, the authors aim to provide an update on the current clinical development status for each drug candidate. The traditional analog approach is insufficient to meet the formidable challenge brought forth by MDR superbugs. With the disappointing results of the genomics approach for delivering novel targets and drug candidates, alternative strategies to permeate the bacterial cell membrane, enhance influx, disrupt efflux, and target specific pathogens via therapeutic antibodies are attractive and promising. Coupled with incentivized business models, governmental policies, and a clarified regulatory pathway, it is hoped that the antibiotic pipeline will be filled with an effective armamentarium to safeguard global health.

Bloodstream Infections in a Neonatal Intensive Care Unit

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Mehmet Sah Ižpek

2016-09-01

Full Text Available Aim: To determine the pattern of bloodstream infections (BSIs and antimicrobial susceptibility of pathogens in a neonatal intensive care unit (NICU.Material and Method: Positive hemoculture of neonates diagnosed with nosocomial sepsis from March 2011 to March 2014 in the NICU of Diyarbakir Maternity and Children%u2019s Hospital, in the southeastern region of Anatolia, Turkey, were retrospectively reviewed. Results: A total of 148 pathogens were isolated in 142 neonates. The most common microorganisms isolated were Klebsiella pneumoniae (40.5% and Acinetobacter baumannii (29.7% which was a result of a hospital outbreak. Multi-drug resistant (MDR strains accounted for 20.0% of K. pneumoniae isolates and 93.2% of A. baumannii isolates. The sepsis-attributable mortality rate was higher in cases infected with MDR strains than in cases infected without MDR strains or Candida spp (24% vs. 9.7%, p=0.032. Discussion: In our unit, BSIs were more often caused by Gram negative bacteria. BSIs caused by MDR strains were associated with a higher rate of sepsis-attributable mortality.

Nosocomial bloodstream infection in a tertiary care paediatric intensive care unit

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Hamid, M.H.; Maqbool, S.

2007-01-01

To determine the frequency, causative organisms and susceptibility pattern of nosocomial bloodstream infections in children. All children admitted to the unit during the study period were daily evaluated for features suggestive of nosocomial infection. In addition to other investigations, blood cultures were done in all suspected cases for the confirmation of nosocomial bloodstream infection (BSI). Nosocomial infection was defined according to the criteria set by Centre for Disease Control and Prevention. Demographic, microbiological and other variables were carefully studied to analyze frequency, incidence rate, spectrum of isolates and susceptibility pattern. Children with and without nosocomial BSI were compared with regard to age, duration of stay in hospital, need and duration of ventilation and the outcome. Of the total 406 admissions, 134 children were suspected to have nosocomial infection on at least 214 occasions (episodes). Blood cultures yielded growth of pathological organisms in 62 of these episodes, giving the frequency of nosocomial BSI as 15.2 per 100 admissions (62/406 episodes). Children with nosocomial bloodstream infection were found to have younger mean age (2.1 vs. 4.1 years), longer average duration of stay (13.1 vs. 6.6 days), more frequent need for ventilation (64% vs. 34%) and longer duration of ventilation (9.7 vs. 4.8 days). Majority of isolates (77%) were gram-negative bacteria; Klebsiella being the most common isolate (n= 23). Aztreonam, Ceftiazidime, Ceforuxime and Ciprofloxacin showed high resistance pattern (33-50%). Isolates showed good sensitivity to Vancomycin (100%), Imipenem (80%), Meropenem (100%) and Co-amoxiclav (88%). The frequency of nosocomial BSI in the observed setting was quite high, having marked impact on the duration of stay and outcome. Emergence of resistant pathogens is alarming. (author)

Bloodstream infection following 217 consecutive systemic-enteric drained pancreas transplants

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Mark Walter

2006-08-01

Full Text Available Abstract Background Combined kidney pancreas transplantation (PTx evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications. Methods 217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole. Results One year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16% with a median onset on day 12 (range 1–45 post transplant. Sepsis source was intraabdominal infection (IAI (n = 21, a contaminated central venous line (n = 10, wound infection (n = 5, urinary tract infection (n = 2 and graft transmitted (n = 2. Nine patients (4% experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11 were isolated from blood. Gram positive cocci accounted for 50 isolates (77%: Coagulase negative staphylococci (n = 28, i.e. 43% (nine multi-resistant, Staphylococcus aureus (n = 11, i.e. 17% (four multi-resistant, enterococci (n = 9, i.e. 14% (one E. faecium. Gram negative rods were cultured in twelve cases (18%. Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036, patient survival was not affected. Conclusion Sepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.

The Growing Threat of Multidrug-Resistant Gram-Negative Infections in Patients with Hematologic Malignancies

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Baker, Thomas M.; Satlin, Michael J.

2016-01-01

Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts. This review characterizes the epidemiology, risk factors, resistance mechanisms, recommended treatments, and outcomes of the MDR Gram-negative bacteria that commonly cause infections in patients with hematologic malignancies. We also examine infection prevention strategies in hematology patients, such as infection control practices, antimicrobial stewardship, and targeted decolonization. Finally, we assess strategies to improve outcomes of infected patients, including gastrointestinal screening to guide empirical antibiotic therapy, new rapid diagnostic tools for expeditious identification of MDR pathogens, and use of two new antimicrobial agents, ceftolozane/tazobactam and ceftazidime/avibactam. PMID:27339405

Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean

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Carlos M. Luna

2014-01-01

Full Text Available This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs. A systematic search of the biomedical literature (PubMed was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%. Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

Gram-negative diabetic foot osteomyelitis: risk factors and clinical presentation.

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Aragón-Sánchez, Javier; Lipsky, Benjamin A; Lázaro-Martínez, Jose L

2013-03-01

Osteomyelitis frequently complicates infections in the feet of patients with diabetes. Gram-positive cocci, especially Staphylococcus aureus, are the most commonly isolated pathogens, but gram-negative bacteria also cause some cases of diabetic foot osteomyelitis (DFO). These gram-negatives require different antibiotic regimens than those commonly directed at gram-positives. There are, however, few data on factors related to their presence and how they influence the clinical picture. We conducted a retrospective study to determine the variables associated with the isolation of gram-negative bacteria from bone samples in cases of DFO and the clinical presentation of these infections. Among 341 cases of DFO, 150 had a gram-negative isolate (alone or combined with a gram-positive isolate) comprising 44.0% of all patients and 50.8% of those with a positive bone culture. Compared with gram-positive infections, wounds with gram-negative organisms more often had a fetid odor, necrotic tissue, signs of soft tissue infection accompanying osteomyelitis, and clinically severe infection. By multivariate analysis, the predictive variables related to an increased likelihood of isolating gram-negatives from bone samples were glycated hemoglobin gram-negatives had a statistically significantly higher prevalence of leukocytosis and higher white blood cell counts than those without gram-negatives. In conclusion, gram-negative organisms were isolated in nearly half of our cases of DFO and were associated with more severe infections, higher white blood cell counts, lower glycated hemoglobin levels, and wounds of traumatic etiology.

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

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Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel

2015-11-01

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.

Associations Between Enteral Colonization With Gram-Negative Bacteria and Intensive Care Unit-Acquired Infections and Colonization of the Respiratory Tract.

Science.gov (United States)

Frencken, Jos F; Wittekamp, Bastiaan H J; Plantinga, Nienke L; Spitoni, Cristian; van de Groep, Kirsten; Cremer, Olaf L; Bonten, Marc J M

2018-02-01

Enteral and respiratory tract colonization with gram-negative bacteria may lead to subsequent infections in critically ill patients. We aimed to clarify the interdependence between gut and respiratory tract colonization and their associations with intensive care unit (ICU)-acquired infections in patients receiving selective digestive tract decontamination (SDD). Colonization status of the rectum and respiratory tract was determined using twice-weekly microbiological surveillance in mechanically ventilated subjects receiving SDD between May 2011 and June 2015 in a tertiary medical-surgical ICU in the Netherlands. Acquisition of infections was monitored daily by dedicated observers. Marginal structural models were used to determine the associations between gram-negative rectal colonization and respiratory tract colonization, ICU-acquired gram-negative infection, and ICU-acquired gram-negative bacteremia. Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram-negative carriage in the rectum during ICU stay. Cumulative incidences of ICU-acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n = 44), respectively. Rectal colonization was an independent risk factor for both respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95% confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95% CI, 1.09-6.03], respectively). Similar associations were observed when Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed separately. Gram-negative rectal colonization tends to be stronger associated with subsequent ICU-acquired gram-negative infections than gram-negative respiratory tract colonization. Gram-negative rectal colonization seems hardly associated with subsequent ICU-acquired gram-negative respiratory tract

Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli.

Science.gov (United States)

Hsu, Jui-Feng; Chang, Hsu-Liang; Tsai, Ming-Ju; Tsai, Ying-Ming; Lee, Yen-Lung; Chen, Pei-Huan; Fan, Wen-Chieh; Su, Yu-Chung; Yang, Chih-Jen

2015-09-30

Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95% confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946-11.447), p port infections. We also found that no local sign of infection was significantly associated with the growth of gram-negative bacilli (p = 0.031). TYCO venous ports, age > 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

The Antibiotic Resistance Profiles of Bacterial Strains Isolated from Patients with Hospital-Acquired Bloodstream and Urinary Tract Infections

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Hamed Ghadiri

2012-01-01

Full Text Available Treatment of nosocomial infections is becoming difficult due to the increasing trend of antibiotics resistance. Current knowledge on antibiotic resistance pattern is essential for appropriate therapy. We aimed to evaluate antibiotic resistance profiles in nosocomial bloodstream and urinary tract pathogens. A total of 129 blood stream and 300 urinary tract positive samples were obtained from patients referring to Besat hospital over a two-year period (2009 and 2010. Antibiotic sensitivity was ascertained using the Kirby-Bauer disk diffusion technique according to CLSI guidelines. Patient's data such as gender and age were recorded. The ratio of gram-negative to gram-positive bacteria in BSIs was 1.6 : 1. The most prevalent BSI pathogen was Coagulase-Negative Staphylococci (CoNS. The highest resistance rate of CoNS was against penicillin (91.1% followed by ampicillin (75.6%, and the lowest rate was against vancomycin (4.4%. Escherichia coli was the most prevalent pathogen isolated from urinary tract infections (UTIs. Ratio of gram-negative to gram-positive bacteria was 3.2 : 1. The highest resistance rate of E. coli isolates was against nalidixic acid (57.7%. The present study showed that CoNS and E. coli are the most common causative agents of nosocomial BSIs and UTIs, and control of infection needs to be addressed in both antibiotic prescription and general hygiene.

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.

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Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J; Zhou, Pei; Sebbane, Florent

2017-07-25

The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria. IMPORTANCE The rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are active in vitro against a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad-spectrum antibiotic targeting LpxC. Hence, the data highlight the therapeutic potential of Lpx

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

Energy Technology Data Exchange (ETDEWEB)

Lemaître, Nadine; Liang, Xiaofei; Najeeb, Javaria; Lee, Chul-Jin; Titecat, Marie; Leteurtre, Emmanuelle; Simonet, Michel; Toone, Eric J.; Zhou, Pei; Sebbane, Florent; Nacy, Carol A.

2017-07-25

The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effectivein vitroagainst a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacteriumYersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

IMPORTANCEThe rapid spread of antimicrobial resistance among Gram-negative bacilli highlights the urgent need for new antibiotics. Here, we describe a new class of antibiotics lacking cross-resistance with conventional antibiotics. The compounds inhibit LpxC, a key enzyme in the lipid A biosynthetic pathway in Gram-negative bacteria, and are activein vitroagainst a broad panel of clinical isolates of Gram-negative bacilli involved in nosocomial and community infections. The present study also constitutes the first demonstration of the curative treatment of bubonic plague by a novel, broad

Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia

Directory of Open Access Journals (Sweden)

Mindy M. Sampson

2017-01-01

Full Text Available Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC

Directory of Open Access Journals (Sweden)

Nadine Lemaître

2017-07-01

Full Text Available The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram-negative bacterial infections. However, experimental proof of this concept is lacking. Here, we describe our discovery and characterization of a biphenylacetylene-based inhibitor of LpxC, an essential enzyme in the biosynthesis of the lipid A component of the outer membrane of Gram-negative bacteria. The compound LPC-069 has no known adverse effects in mice and is effective in vitro against a broad panel of Gram-negative clinical isolates, including several multiresistant and extremely drug-resistant strains involved in nosocomial infections. Furthermore, LPC-069 is curative in a murine model of one of the most severe human diseases, bubonic plague, which is caused by the Gram-negative bacterium Yersinia pestis. Our results demonstrate the safety and efficacy of LpxC inhibitors as a new class of antibiotic against fatal infections caused by extremely virulent pathogens. The present findings also highlight the potential of LpxC inhibitors for clinical development as therapeutics for infections caused by multidrug-resistant bacteria.

Sinus surgery postpones chronic Gram-negative lung infection

DEFF Research Database (Denmark)

Alanin, M C; Aanaes, K; Høiby, N

2016-01-01

of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined......BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency....... The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three...

Rapid and reliable identification of Gram-negative bacteria and Gram-positive cocci by deposition of bacteria harvested from blood cultures onto the MALDI-TOF plate.

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Barnini, Simona; Ghelardi, Emilia; Brucculeri, Veronica; Morici, Paola; Lupetti, Antonella

2015-06-18

Rapid identification of the causative agent(s) of bloodstream infections using the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) methodology can lead to increased empirical antimicrobial therapy appropriateness. Herein, we aimed at establishing an easier and simpler method, further referred to as the direct method, using bacteria harvested by serum separator tubes from positive blood cultures and placed onto the polished steel target plate for rapid identification by MALDI-TOF. The results by the direct method were compared with those obtained by MALDI-TOF on bacteria isolated on solid media. Identification of Gram-negative bacilli was 100 % concordant using the direct method or MALDI-TOF on isolated bacteria (96 % with score > 2.0). These two methods were 90 % concordant on Gram-positive cocci (32 % with score > 2.0). Identification by the SepsiTyper method of Gram-positive cocci gave concordant results with MALDI-TOF on isolated bacteria in 87 % of cases (37 % with score > 2.0). The direct method herein developed allows rapid identification (within 30 min) of Gram-negative bacteria and Gram-positive cocci from positive blood cultures and can be used to rapidly report reliable and accurate results, without requiring skilled personnel or the use of expensive kits.

Multiplex identification of sepsis-causing Gram-negative pathogens from the plasma of infected blood.

Science.gov (United States)

Chung, Boram; Park, Chulmin; Cho, Sung-Yeon; Shin, Juyoun; Shin, Sun; Yim, Seon-Hee; Lee, Dong-Gun; Chung, Yeun-Jung

2018-02-01

Early and accurate detection of bacterial pathogens in the blood is the most crucial step for sepsis management. Gram-negative bacteria are the most common organisms causing severe sepsis and responsible for high morbidity and mortality. We aimed to develop a method for rapid multiplex identification of clinically important Gram-negative pathogens and also validated whether our system can identify Gram-negative pathogens with the cell-free plasm DNA from infected blood. We designed five MLPA probe sets targeting the genes specific to major Gram-negative pathogens (uidA and lacY for E. coli, ompA for A. baumannii, phoE for K. pneumoniae, and ecfX for P. aeruginosa) and one set targeting the CTX-M group 1 to identify the ESBL producing Gram-negative pathogens. All six target-specific peaks were clearly separated without any non-specific peaks in a multiplex reaction condition. The minimum detection limit was 100 fg of pathogen DNA. When we tested 28 Gram-negative clinical isolates, all of them were successfully identified without any non-specific peaks. To evaluate the clinical applicability, we tested seven blood samples from febrile patients. Three blood culture positive cases showed E. coli specific peaks, while no peak was detected in the other four culture negative samples. This technology can be useful for detection of major sepsis-causing, drug-resistant Gram-negative pathogens and also the major ESBL producing Gram-negatives from the blood of sepsis patients in a clinical setting. This system can help early initiation of effective antimicrobial treatment against Gram-negative pathogens for sepsis patients, which is very crucial for better treatment outcomes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bloodstream Infections with Mycobacterium tuberculosis among HIV patients

Centers for Disease Control (CDC) Podcasts

This podcast looks at bloodstream infections with Mycobacterium tuberculosis and other pathogens among outpatients infected with HIV in Southeast Asia. CDC health scientist Kimberly McCarthy discusses the study and why bloodstream infections occur in HIV-infected populations.

Exploring the hidden potential of fosfomycin for the fight against severe Gram-negative infections

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P V Saiprasad

2016-01-01

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.

Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection

International Nuclear Information System (INIS)

Ramsay, Stuart C.; Maggs, Jacqueline A.; Ketheesan, Natkunam; Norton, Robert; LaBrooy, Justin

2005-01-01

Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid ( 99m Tc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99m Tc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

Science.gov (United States)

Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

2014-12-01

We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

Silver enhances antibiotic activity against gram-negative bacteria.

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Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

2013-06-19

A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

Synergistic antibacterial effect of silver and ebselen against multidrug-resistant Gram-negative bacterial infections.

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Zou, Lili; Lu, Jun; Wang, Jun; Ren, Xiaoyuan; Zhang, Lanlan; Gao, Yu; Rottenberg, Martin E; Holmgren, Arne

2017-08-01

Multidrug-resistant (MDR) Gram-negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult-to-treat MDR Gram-negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria. Silver ions were identified as strong inhibitors of Escherichia coli thioredoxin and thioredoxin reductase, which are required for ribonucleotide reductase and DNA synthesis and defense against oxidative stress. The bactericidal efficacy of silver and ebselen was further verified in the treatment of mild and acute MDR E. coli peritonitis in mice. These results demonstrate that thiol-dependent redox systems in bacteria can be targeted in the design of new antibacterial drugs. The silver and ebselen combination offers a proof of concept in targeting essential bacterial systems and might be developed for novel efficient treatments against MDR Gram-negative bacterial infections. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Development of a Multiplexed Microsphere PCR for Culture-Free Detection and Gram-Typing of Bacteria in Human Blood Samples.

Science.gov (United States)

Liang, Fang; Browne, Daniel J; Gray, Megan J; Gartlan, Kate H; Smith, David D; Barnard, Ross T; Hill, Geoffrey R; Corrie, Simon R; Markey, Kate A

2018-05-11

Bloodstream infection is a significant clinical problem, particularly in vulnerable patient groups such as those undergoing chemotherapy and bone marrow transplantation. Clinical diagnostics for suspected bloodstream infection remain centered around blood culture (highly variable timing, in the order of hours to days to become positive), and empiric use of broad-spectrum antibiotics is therefore employed for patients presenting with febrile neutropenia. Gram-typing provides the first opportunity to target therapy (e.g., combinations containing vancomycin or teicoplanin for Gram-positives; piperacillin-tazobactam or a carbapenem for Gram-negatives); however, current approaches require blood culture. In this study, we describe a multiplexed microsphere-PCR assay with flow cytometry readout, which can distinguish Gram-positive from Gram-negative bacterial DNA in a 3.5 h time period. The combination of a simple assay design (amplicon-dependent release of Gram-type specific Cy3-labeled oligonucleotides) and the Luminex-based readout (for quantifying each specific Cy3-labeled sequence) opens opportunities for further multiplexing. We demonstrate the feasibility of detecting common Gram-positive and Gram-negative organisms after spiking whole bacteria into healthy human blood prior to DNA extraction. Further development of DNA extraction methods is required to reach detection limits comparable to blood culture.

The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients

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Mücahit Yemişen

2016-08-01

Full Text Available Objective: Patients receiving hematopoietic stem cell transplantation (HSCT are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62% and allogeneic (38% HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28% and Hodgkin lymphoma (21.5%. A total of 142 (45% patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011, and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2% and Acinetobacter baumannii (8.8% were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

Blood culture gram stain, acridine orange stain and direct sensitivity-based antimicrobial therapy of bloodstream infection in patients with trauma.

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Behera, B; Mathur, P; Gupta, B

2010-01-01

The purpose of this study was to ascertain if the simple practice of Gram stain, acridine orange stain and direct sensitivity determination of positive blood culture bottles could be used to guide early and appropriate treatment in trauma patients with clinical suspicion of sepsis. The study also aimed to evaluate the error in interpreting antimicrobial sensitivity by direct method when compared to standard method and find out if specific antibiotic-organism combination had more discrepancies. Findings from consecutive episodes of blood stream infection at an Apex Trauma centre over a 12-month period are summarized. A total of 509 consecutive positive blood cultures were subjected to Gram staining. AO staining was done in BacT/ALERT-positive Gram-stain negative blood cultures. Direct sensitivity was performed from 369 blood culture broths, showing single type of growth in Gram and acridine orange staining. Results of direct sensitivity were compared to conventional sensitivity for errors. No 'very major' discrepancy was found in this study. About 5.2 and 1.8% minor error rates were noted in gram-positive and gram-negative bacteria, respectively, while comparing the two methods. Most of the discrepancies in gram-negative bacteria were noted in beta lactam - beta lactamase inhibitor combinations. Direct sensitivity testing was not reliable for reporting of methicillin and vancomycin resistance in Staphylococci. Gram stain result together with direct sensitivity testing is required for optimizing initial antimicrobial therapy in trauma patients with clinical suspicion of sepsis. Gram staining and AO staining proved particularly helpful in the early detection of candidaemia.

Bloodstream Infections with Mycobacterium tuberculosis among HIV patients

Centers for Disease Control (CDC) Podcasts

2010-09-23

This podcast looks at bloodstream infections with Mycobacterium tuberculosis and other pathogens among outpatients infected with HIV in Southeast Asia. CDC health scientist Kimberly McCarthy discusses the study and why bloodstream infections occur in HIV-infected populations.  Created: 9/23/2010 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/23/2010.

DMPD: Lipopolysaccharide sensing an important factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of LPShypersensitivity. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available se toGram-negative bacterial infections: benefits and hazards of LPShypersensitivity. Freudenberg MA, Tchapt...portant factor in the innate immune response toGram-negative bacterial infections: benefits and hazards of L...une response toGram-negative bacterial infections: benefits and hazards of LPShyp

An optimized staining technique for the detection of Gram positive and Gram negative bacteria within tissue.

Science.gov (United States)

Becerra, Sandra C; Roy, Daniel C; Sanchez, Carlos J; Christy, Robert J; Burmeister, David M

2016-04-12

Bacterial infections are a common clinical problem in both acute and chronic wounds. With growing concerns over antibiotic resistance, treatment of bacterial infections should only occur after positive diagnosis. Currently, diagnosis is delayed due to lengthy culturing methods which may also fail to identify the presence of bacteria. While newer costly bacterial identification methods are being explored, a simple and inexpensive diagnostic tool would aid in immediate and accurate treatments for bacterial infections. Histologically, hematoxylin and eosin (H&E) and Gram stains have been employed, but are far from optimal when analyzing tissue samples due to non-specific staining. The goal of the current study was to develop a modification of the Gram stain that enhances the contrast between bacteria and host tissue. A modified Gram stain was developed and tested as an alternative to Gram stain that improves the contrast between Gram positive bacteria, Gram negative bacteria and host tissue. Initially, clinically relevant strains of Pseudomonas aeruginosa and Staphylococcus aureus were visualized in vitro and in biopsies of infected, porcine burns using routine Gram stain, and immunohistochemistry techniques involving bacterial strain-specific fluorescent antibodies as validation tools. H&E and Gram stain of serial biopsy sections were then compared to a modification of the Gram stain incorporating a counterstain that highlights collagen found in tissue. The modified Gram stain clearly identified both Gram positive and Gram negative bacteria, and when compared to H&E or Gram stain alone provided excellent contrast between bacteria and non-viable burn eschar. Moreover, when applied to surgical biopsies from patients that underwent burn debridement this technique was able to clearly detect bacterial morphology within host tissue. We describe a modification of the Gram stain that provides improved contrast of Gram positive and Gram negative microorganisms within host

Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram-negative pathogens

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Hsu Wei-Hsiu

2011-01-01

Full Text Available Abstract Background Monomicrobial necrotizing fasciitis is rapidly progressive and life-threatening. This study was undertaken to ascertain whether the clinical presentation and outcome for patients with this disease differ for those infected with a gram-positive as compared to gram-negative pathogen. Methods Forty-six patients with monomicrobial necrotizing fasciitis were examined retrospectively from November 2002 to January 2008. All patients received adequate broad-spectrum antibiotic therapy, aggressive resuscitation, prompt radical debridement and adjuvant hyperbaric oxygen therapy. Eleven patients were infected with a gram-positive pathogen (Group 1 and 35 patients with a gram-negative pathogen (Group 2. Results Group 2 was characterized by a higher incidence of hemorrhagic bullae and septic shock, higher APACHE II scores at 24 h post-admission, a higher rate of thrombocytopenia, and a higher prevalence of chronic liver dysfunction. Gouty arthritis was more prevalent in Group 1. For non-survivors, the incidences of chronic liver dysfunction, chronic renal failure and thrombocytopenia were higher in comparison with those for survivors. Lower level of serum albumin was also demonstrated in the non-survivors as compared to those in survivors. Conclusions Pre-existing chronic liver dysfunction, chronic renal failure, thrombocytopenia and hypoalbuminemia, and post-operative dependence on mechanical ventilation represent poor prognostic factors in monomicrobial necrotizing fasciitis. Patients with gram-negative monobacterial necrotizing fasciitis present with more fulminant sepsis.

Distribution of multi-resistant Gram-negative versus Gram-positive bacteria in the hospital inanimate environment.

Science.gov (United States)

Lemmen, S W; Häfner, H; Zolldann, D; Stanzel, S; Lütticken, R

2004-03-01

We prospectively studied the difference in detection rates of multi-resistant Gram-positive and multi-resistant Gram-negative bacteria in the inanimate environment of patients harbouring these organisms. Up to 20 different locations around 190 patients were surveyed. Fifty-four patients were infected or colonized with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) and 136 with multi-resistant Gram-negative bacteria. The environmental detection rate for MRSA or VRE was 24.7% (174/705 samples) compared with 4.9% (89/1827 samples) for multi-resistant Gram-negative bacteria (PGram-positive bacteria were isolated more frequently than Gram-negatives from the hands of patients (PGram-positive and Gram-negative isolates. Our results suggest that the inanimate environment serves as a secondary source for MRSA and VRE, but less so for Gram-negative bacteria. Thus, strict contact isolation in a single room with complete barrier precautions is recommended for MRSA or VRE; however, for multi-resistant Gram-negative bacteria, contact isolation with barrier precautions for close contact but without a single room seems sufficient. This benefits not only the patients, but also the hospital by removing some of the strain placed on already over-stretched resources.

Costs and length of stay associated with antimicrobial resistance in acute kidney injury patients with bloodstream infection.

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Vandijck, D M; Blot, S I; Decruyenaere, J M; Vanholder, R C; De Waele, J J; Lameire, N H; Claus, S; De Schuijmer, J; Dhondt, A W; Verschraegen, G; Hoste, E A

2008-01-01

Antimicrobial resistance negatively impacts on prognosis. Intensive care unit (ICU) patients, and particularly those with acute kidney injury (AKI), are at high risk for developing nosocomial bloodstream infections (BSI) due to multi-drug-resistant strains. Economic implications in terms of costs and length of stay (LOS) attributable to antimicrobial resistance are underevaluated. This study aimed to assess whether microbial susceptibility patterns affect costs and LOS in a well-defined cohort of ICU patients with AKI undergoing renal replacement therapy (RRT) who developed nosocomial BSI. Historical study (1995-2004) enrolling all adult RRT-dependent ICU patients with AKI and nosocomial BSI. Costs were considered as invoiced in the Belgian reimbursement system, and LOS was used as a surrogate marker for hospital resource allocation. Of the 1330 patients with AKI undergoing RRT, 92 had microbiologic evidence of nosocomial BSI (57/92, 62% due to a multi-drug-resistant microorganism). Main patient characteristics were equal in both groups. As compared to patients with antimicro-4 bial-susceptible BSI, patients with antimicrobial-resistant BSI were more likely to acquire Gram-positive infection (72.6% vs 25.5%, P0.05) or hospital costs (all P>0.05) when comparing patients with antimicrobial-resistant vs antimicrobial-susceptible BSI. However, although not statistically significant, patients with BSI caused by resistant Gram-negative-, Candida-, or anaerobic bacteria incurred substantial higher costs than those without. In a cohort of ICU patients with AKI and nosocomial BSI undergoing RRT, patients with antimicrobial-resistant vs antimicrobial-susceptible Gram-positive BSI did not have longer hospital stays, or higher hospital costs. Patients with resistant "other" (i.e. Gram-negative, Candida, or anaerobic) BSI were found to have a distinct trend towards increased resources use as compared to patients with susceptible "other" BSI, respectively.

Candida Infection of the Bloodstream - Candidemia

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Candida Infection of the Bloodstream– Candidemia Fungal Disease Series #4 Candida is the single most important cause of fungal infections worldwide. In the U.S., Candida is the 4th most common cause of bloodstream ...

Long-term outcome of acute prosthetic joint infections due to gram-negative bacilli treated with retention of prosthesis.

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Jaén, N; Martínez-Pastor, J C; Muñoz-Mahamud, E; García-Ramiro, S; Bosch, J; Mensa, J; Soriano, A

2012-09-01

To update the clinical information of the 47 patients with a prosthetic joint infection due to Gram-negative bacilli included in a previous study and to reassess the predictors of failure after a longer follow-up. Using the electronic files of our hospital, all the information regarding readmissions to the hospital, new surgical procedures and the reason for the new surgery (infection, aseptic loosening), and the last visit in the hospital were registered. The medical chart of the 35 patients that were considered in remission in the previous publication was reviewed. In 30 patients no clinical evidence of failure was detected and no additional surgery on the previously infected prosthesis was necessary and they were considered in long-term remission. In 5 cases a late complication was identified. One case had a reinfection due to coagulase-negative staphylococci after 22 months from the open debridement and required a 2-stage revision surgery. The other 4 cases developed an aseptic loosening and it was necessary to perform a 1-stage exchange. Receiving a fluoroquinolone when all the Gram-negatives involved in the infection were susceptible to fluoroquinolones was the only factor associated with remission in the univariate analysis (p=0.002). After a long-term follow-up, our results support the importance of using fluoroquinolones in acute PJI due to Gram-negative bacilli.

Drug-resistant gram-negative uropathogens: A review.

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Khoshnood, Saeed; Heidary, Mohsen; Mirnejad, Reza; Bahramian, Aghil; Sedighi, Mansour; Mirzaei, Habibollah

2017-10-01

Urinary tract infection(UTI) caused by Gram-negative bacteria is the second most common infectious presentation in community medical practice. Approximately 150 million people are diagnosed with UTI each year worldwide. Drug resistance in Gram-negative uropathogens is a major global concern which can lead to poor clinical outcomes including treatment failure, development of bacteremia, requirement for intravenous therapy, hospitalization, and extended length of hospital stay. The mechanisms of drug resistance in these bacteria are important due to they are often not identified by routine susceptibility tests and have an exceptional potential for outbreaks. Treatment of UTIs depends on the access to effective drugs, which is now threatened by antibiotic resistant Gram-negative uropathogens. Although several effective antibiotics with activity against highly resistant Gram-negatives are available, there is not a unique antibiotic with activity against the high variety of resistance. Therefore, antimicrobial susceptibility tests, correlation between clinicians and laboratories, development of more rapid diagnostic methods, and continuous monitoring of drug resistance are urgent priorities. In this review, we will discuss about the current global status of drug-resistant Gram-negative uropathogens and their mechanisms of drug resistance to provide new insights into their treatment options. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Catheter-related bloodstream infection.

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Goede, Matthew R; Coopersmith, Craig M

2009-04-01

Catheter-related bloodstream infections (CR-BSIs) are a common, frequently preventable complication of central venous catheterization. CR-BSIs can be prevented by strict attention to insertion and maintenance of central venous catheters and removing unneeded catheters as soon as possible. Antiseptic- or antibiotic-impregnated catheters are also an effective tool to prevent infections. The diagnosis of CR-BSI is made largely based on culture results. CR-BSIs should always be treated with antibiotics, and except in rare circumstances the infected catheter needs to be removed.

Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

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McNicholas, Sinead; Talento, Alida Fe; O'Gorman, Joanne; Hannan, Margaret M; Lynch, Maureen; Greene, Catherine M; Humphreys, Hilary; Fitzgerald-Hughes, Deirdre

2014-11-15

The clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patients with different clinical courses of infection. A prospective study was carried out in 61 patients with S. aureus bloodstream infection and circulating levels of IL-6, GRO-γ, RANTES and leptin were assessed over the course of the infection. Levels were compared in patients with complicated courses of infection (e.g. infective endocarditis) versus uncomplicated courses of S. aureus bloodstream infection and methicillin-resistant S. aureus Vs methicillin-susceptible S. aureus infection. Significantly lower leptin levels (p < 0.05) and significantly higher IL-6 levels (p < 0.05) were detected at laboratory diagnosis in patients with complicated compared to uncomplicated S. aureus bloodstream infection. Significantly higher levels of GRO-γ were associated with MRSA infection compared to MSSA infection. IL-6 may be an early inflammatory marker of complicated S. aureus bloodstream infection. Leptin may be protective against the development of a complicated S. aureus bloodstream infection.

Should gram stains have a role in diagnosing hip arthroplasty infections?

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Johnson, Aaron J; Zywiel, Michael G; Stroh, D Alex; Marker, David R; Mont, Michael A

2010-09-01

The utility of Gram stains in diagnosing periprosthetic infections following total hip arthroplasty has recently been questioned. Several studies report low sensitivity of the test, and its poor ability to either confirm or rule out infection in patients undergoing revision total hip arthroplasty. Despite this, many institutions including that of the senior author continue to perform Gram stains during revision total hip arthroplasty. We assessed the sensitivity, specificity, accuracy, and positive and negative predictive values of Gram stains from surgical-site samplings taken from procedures on patients with both infected and aseptic revision total hip arthroplasties. A review was performed on patients who underwent revision total hip arthroplasty between 2000 and 2007. Eighty-two Gram stains were performed on patients who had infected total hip arthroplasties and underwent revision procedures. Additionally, of the 410 revision total hip arthroplasties performed on patients who were confirmed infection-free, 120 Gram stains were performed. Patients were diagnosed as infected using multiple criteria at the time of surgery. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated from these Gram stain results. The Gram stain demonstrated a sensitivity and specificity of 9.8% and 100%, respectively. In this series, the Gram stain had a negative predictive value of 62%, a positive predictive value of 100%, and an accuracy of 63%. Gram stains obtained from surgical-site samples had poor sensitivity and poor negative predictive value. Based on these findings, as well as those of other authors, we believe that Gram stains should no longer be considered for diagnosing infections in revision total hip arthroplasty. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

[Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias].

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Duszyńska, Wiesława

2010-01-01

Multidrug-resistant Gram-negative bacteria pose a serious and rapidly emerging threat to patients in healthcare settings, and are especially prevalent and problematic in intensive therapy units. Recently, the emergence of pandrug-resistance in Gram-negative bacteria poses additional concerns. This review examines the clinical impact and epidemiology of multidrug-resistant Gram-negative bacteria as a cause of increased morbidity and mortality among ITU patients. Beta-lactamases, cephalosporinases and carbapenemases play the most important role in resistance to antibiotics. Despite the tendency to increased resistance, carbapenems administered by continuous infusion remain the most effective drugs in severe sepsis. Drug concentration monitoring, albeit rarely used in practice, is necessary to ensure an effective therapeutic effect.

Ten-year surveillance of nosocomial bloodstream infections: trends of aetiology and antimicrobial resistance in a comprehensive cancer centre.

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Passerini, R; Ghezzi, Tl; Sandri, Mt; Radice, D; Biffi, R

2011-01-01

Bloodstream infections (BSIs) are one of the major life-threatening infectious conditions in cancer patients and are responsible for prolonged hospital stays, high healthcare costs and significant mortality. Several clinical trials have reported an improved survival in patients treated with appropriate empirical broad-spectrum antibiotic therapy. Early detection of pathogens and determination of their susceptibility are essential for the optimization of treatment. Variability between hospitals is substantial and requires the individual analysis of local trends. The aim of this study is to assess the local epidemiology of BSI in a single cancer centre over a 10-year period. Retrospective microbiological surveillance of all febrile/infective episodes occurring in oncological and surgical patients in a high-volume cancer centre between January 1999 and December 2008 were considered. Patients' data were collected, processed and analyzed using the epidemiological resource of the Virtuoso Plus software (Metafora Informatica Srl, Milano, Italy). Spearman's rank correlation coefficient, including the two-tailed test of significance, was used to investigate trends of incidence and rate of antibiotic resistance over the 10-year period. A total of 13,058 blood cultures (BCs) were performed in 2,976 patients. BCs were positive in 2,447 tests, representing 740 infective/febrile episodes: 358 (48%) in medical oncology and 382 (52%) in surgical wards. Gram-positives were responsible for the majority of episodes in oncological and surgical divisions (about 63% and 55%, respectively). Gram-positives were also the most common organism in non-catheter-related BSIs (CRBSIs) both in medical oncology (75%) and in surgical divisions (50%). Enterococci showed an increased resistance to levofloxacin, from 5.6% to 25.7% (p = 0.02) and to erythromycin, from 41.7% to 61.4%, (p = 0.05). Similarly, coagulase negative staphylococci (CoNS) developed resistance to levofloxacin and ciprofloxacin

Relationship between neighborhood poverty rate and bloodstream infections in the critically ill.

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Mendu, Mallika L; Zager, Sam; Gibbons, Fiona K; Christopher, Kenneth B

2012-05-01

Poverty is associated with increased risk of chronic illness, but its contribution to bloodstream infections is not well-defined. We performed a multicenter observational study of 14,657 patients, aged 18 yrs or older, who received critical care and had blood cultures drawn between 1997 and 2007 in two hospitals in Boston, Massachusetts. Data sources included 1990 U.S. Census and hospital administrative data. Census tracts were used as the geographic units of analysis. The exposure of interest was neighborhood poverty rate categorized as 40%. Neighborhood poverty rate is the percentage of residents with income below the federal poverty line. The primary end point was bloodstream infection occurring 48 hrs before critical care initiation to 48 hrs after. Associations between neighborhood poverty rate and bloodstream infection were estimated by logistic regression models. Adjusted odds ratios were estimated by multivariable logistic regression models. Two thousand four-hundred thirty-five patients had bloodstream infections. Neighborhood poverty rate was a strong predictor of risk of bloodstream infection, with a significant risk gradient across neighborhood poverty rate quintiles. After multivariable analysis, neighborhood poverty rate in the highest quintiles (20%-40% and >40%) were associated with a 26% and 49% increase in bloodstream infection risk, respectively, relative to patients with neighborhood poverty rate of poverty rate, a proxy for decreased socioeconomic status, appears to be associated with risk of bloodstream infection among patients who receive critical care.

Sinus surgery postpones chronic gram-negative lung infection

DEFF Research Database (Denmark)

Alanin, M C; Aanaes, K; Høiby, N

2016-01-01

Background: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency...

The comparison of pyrosequencing molecular Gram stain, culture, and conventional Gram stain for diagnosing orthopaedic infections.

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Kobayashi, Naomi; Bauer, Thomas W; Tuohy, Marion J; Lieberman, Isador H; Krebs, Viktor; Togawa, Daisuke; Fujishiro, Takaaki; Procop, Gary W

2006-08-01

We have developed a combined real-time PCR and pyrosequencing assay that successfully differentiated the vast majority of gram-positive and gram-negative bacteria when bacterial isolates were tested. The purpose of this study was to evaluate this assay on clinical specimens obtained from orthopedic surgeries, and to prospectively compare the results of "molecular Gram stain" with culture and conventional direct Gram stain. Forty-five surgical specimens were obtained from patients who underwent orthopedic surgery procedures. The DNA was extracted and a set of broad-range PCR primers that targeted a part of the 16S rDNA gene was used for pan-bacterial PCR. The amplicons were submitted for pyrosequencing and the resulting molecular Gram stain characteristics were recorded. Culture and direct Gram staining were performed using standard methods for all cases. Surgical specimens were reviewed histologically for all cases that had a discrepancy between culture and molecular results. There was an 86.7% (39/45) agreement between the traditional and molecular methods. In 12/14 (85.7%) culture-proven cases of bacterial infection, molecular Gram stain characteristics were in agreement with the culture results, while the conventional Gram stain result was in agreement only for five cases (35.7%). In the 31 culture negative cases, 27 cases were also PCR negative, whereas 4 were PCR positive. Three of these were characterized as gram negative and one as gram positive by this molecular method. Molecular determination of the Gram stain characteristics of bacteria that cause orthopedic infections may be achieved, in most instances, by this method. Further studies are necessary to understand the clinical importance of PCR-positive/culture-negative results.

Temporal Trends in Enterobacter Species Bloodstream Infection: A Population-Based Study, 1998-2007

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Al-Hasan, Majdi N.; Lahr, Brian D.; Eckel-Passow, Jeanette E.; Baddour, Larry M.

2010-01-01

Enterobacter species are the fourth most common cause of gram-negative bloodstream infection (BSI). We examined temporal changes and seasonal variation in the incidence rate of Enterobacter spp. BSI, estimated 28-day and 1-year mortality, and determined in vitro antimicrobial resistance rates of Enterobacter spp. bloodstream isolates in Olmsted County, Minnesota, from 1/1/1998 to 12/31/2007. Multivariable Poisson regression was used to examine temporal changes and seasonal variation in incidence rate and Kaplan-Meier method to estimate 28-day and 1-year mortality. The median age of patients with Enterobacter spp. BSI was 58 years and 53% were female. The overall age- and gender-adjusted incidence rate of Enterobacter spp. BSI was 3.3/100,000 person-years (95% confidence interval [CI]: 2.3-4.4). There was a linear trend of increasing incidence rate from 0.8 (95% CI: 0-1.9) to 6.2 (95% CI: 3.0-9.3) per 100,000 person-years between 1998 and 2007 (p=0.002). There was no significant difference in the incidence rate of Enterobacter spp. BSI during the warmest four months compared to the remainder of the year (incidence rate ratio 1.06 [95% CI: 0.47-2.01]). The overall 28-day and 1-year mortality rates of Enterobacter spp. BSI were 21% (95% CI: 8-34%) and 38% (95% CI: 22-53%), respectively. Up to 13% of Enterobacter spp. bloodstream isolates were resistant to third-generation cephalosporins. To our knowledge, this is the first population-based study to describe the epidemiology and outcome of Enterobacter spp. BSI. The increase in incidence rate of Enterobacter spp. BSI over the past decade, coupled with its associated antimicrobial resistance, dictate more investigation of this syndrome. PMID:20518795

Bloodstream infection in patients with end-stage renal disease in a teaching hospital in central-western Brazil

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Tamara Trelha Gauna

2013-08-01

Full Text Available Introduction Vascular access in patients undergoing hemodialysis is considered a critical determinant of bloodstream infection (BSI and is associated with high morbidity and mortality. The purpose of this study was to investigate the occurrence of BSI in patients with end-stage renal disease using central venous catheters for hemodialysis. Methods A cohort study was conducted in a public teaching hospital in central-western Brazil from April 2010 to December 2011. For every patient, we noted the presence of hyperemia/exudation upon catheter insertion, as well as fever, shivering, and chills during hemodialysis. Results Fifty-nine patients were evaluated. Thirty-five (59.3% patients started dialysis due to urgency, 37 (62.7% had BSI, and 12 (20% died. Hyperemia at the catheter insertion site (64.9% was a significant clinical manifestation in patients with BSI. Statistical analysis revealed 1.7 times more cases of BSI in patients with hypoalbuminemia compared with patients with normal albumin levels. The principal infective agents identified in blood cultures and catheter-tip cultures were Staphylococcus species (24 cases, non-fermentative Gram-negative bacilli (7 cases of Stenotrophomonas maltophilia and 5 cases of Chryseobacterium indologenes, and Candida species (6. Among the Staphylococci identified, 77.7% were methicillin-resistant, coagulase-negative Staphylococci. Of the bacteria isolated, the most resistant were Chryseobacterium indologenes and Acinetobacter baumannii. Conclusions Blood culture was demonstrated to be an important diagnostic test and identified over 50% of positive BSI cases. The high frequency of BSI and the isolation of multiresistant bacteria were disturbing findings. Staphylococcus aureus was the most frequently isolated microorganism, although Gram-negative bacteria predominated overall. These results highlight the importance of infection prevention and control measures in dialysis units.

Pediatric bloodstream infections in Cambodia, 2007 to 2011.

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Stoesser, Nicole; Moore, Catrin E; Pocock, Joanna M; An, Khun Peng; Emary, Kate; Carter, Michael; Sona, Soeng; Poda, Sar; Day, Nicholas; Kumar, Varun; Parry, Christopher M

2013-07-01

Pediatric bacterial bloodstream infections (BSIs) are a major cause of morbidity and mortality worldwide. Epidemiological data from resource-limited settings in southeast Asia, such as Cambodia, are sparse but have important implications for treatment and public health strategies. We retrospectively investigated BSI in children at a pediatric hospital and its satellite clinic in Siem Reap, Cambodia, from January 1, 2007, to July 31, 2011. The range of bacterial pathogens and their antimicrobial susceptibility patterns were analyzed in conjunction with demographic, clinical and outcome data. Of 7682 blood cultures with results (99.9% of cultures taken), 606 (7.9%) episodes of BSI were identified in 588 children. The incidence of BSI increased from 14 to 50/1000 admissions (P < 0.001); this was associated with an increased sampling rate. Most BSI were community acquired (89.1%). Common pathogens included Salmonella Typhi (22.8% of all isolates), Staphylococcus aureus (12.2%), Streptococcus pneumoniae (10.0%), Klebsiella pneumoniae (6.4%) and Escherichia coli (6.3%). 21.5% of BSI were caused by a diverse group of uncommon organisms, the majority of which were environmental Gram-negative species. No Listeria monocytogenes or Group B streptococcal BSI were identified. Antimicrobial resistance, particularly among the Enterobacteriaceae, was common. Overall mortality was substantial (19.0%), higher in neonates (36.9%) and independently associated with meningitis/meningoencephalitis and K. pneumoniae infection. BSI is a common problem in Cambodian children attending hospital and associated with significant mortality. Further studies are needed to clarify the epidemiology of neonatal sepsis, the contribution of atypical organisms and the epidemiology of pneumococcal disease before the introduction of vaccine.

Resistance trends in gram-negative bacteria: surveillance results from two Mexican hospitals, 2005–2010

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Morfin-Otero Rayo

2012-06-01

Full Text Available Abstract Background Hospital-acquired infections caused by multiresistant gram-negative bacteria are difficult to treat and cause high rates of morbidity and mortality. The analysis of antimicrobial resistance trends of gram-negative pathogens isolated from hospital-acquired infections is important for the development of antimicrobial stewardship programs. The information obtained from antimicrobial resistant programs from two hospitals from Mexico will be helpful in the selection of empiric therapy for hospital-acquired gram-negative infections. Findings Two thousand one hundred thirty two gram-negative bacteria collected between January 2005 and December 2010 from hospital-acquired infections occurring in two teaching hospitals in Mexico were evaluated. Escherichia coli was the most frequently isolated gram-negative bacteria, with >50% of strains resistant to ciprofloxacin and levofloxacin. Klebsiella spp. showed resistance rates similar to Escherichia coli for ceftazidime (33.1% vs 33.2%, but exhibited lower rates for levofloxacin (18.2% vs 56%. Of the samples collected for the third most common gram-negative bacteria, Pseudomonas aeruginosa, >12.8% were resistant to the carbapenems, imipenem and meropenem. The highest overall resistance was found in Acinetobacter spp. Enterobacter spp. showed high susceptibility to carbapenems. Conclusions E. coli was the most common nosocomial gram-negative bacilli isolated in this study and was found to have the second-highest resistance to fluoroquinolones (>57.9%, after Acinetobacter spp. 81.2%. This finding represents a disturbing development in a common nosocomial and community pathogen.

Community-acquired multidrug-resistant Gram-negative bacterial infective endocarditis.

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Naha, Sowjanya; Naha, Kushal; Acharya, Vasudev; Hande, H Manjunath; Vivek, G

2014-08-05

We describe two cases of bacterial endocarditis secondary to multidrug-resistant Gram-negative organisms. In both cases, the diagnosis was made in accordance with the modified Duke's criteria and confirmed by histopathological analysis. Furthermore, in both instances there were no identifiable sources of bacteraemia and no history of contact with hospital or other medical services prior to the onset of symptoms. The patients were managed in similar fashion with prolonged broad-spectrum antibiotic therapy and surgical intervention and made complete recoveries. These cases highlight Gram-negative organisms as potential agents for endocarditis, as well as expose the dissemination of such multidrug-resistant bacteria into the community. The application of an integrated medical and surgical approach and therapeutic dilemmas encountered in managing these cases are described. 2014 BMJ Publishing Group Ltd.

Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.

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Bunke, C M; Brier, M E; Golper, T A

1997-08-01

The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus

Extended spectrum beta-lactamases in urinary gram-negative bacilli and their susceptibility pattern

International Nuclear Information System (INIS)

Mumtaz, S.

2008-01-01

Beta-lactamases of gram-negative bacteria are the most important mechanism of resistance against beta lactams. Two types of beta-lactamases can confer resistance against third generation cephalosporins inducible Chromosomal beta -lactamases and extended-spectrum beta-lactamases. The extended-spectrum beta lactamases producing Strains of Enterobacteriaceae have emerged as a major problem in hospitalized as well as community based infections resulting in range of infections from uncomplicated urinary tract infection to life threatening sepsis. The study was conducted at the Microbiology Department of Fauji Foundation Hospital, Rawalpindi over a period of two years (April 2004-March 2006). Multidrug resistance and extended spectrum beta-lactamases production was studied in 111 enteric Gram-negative bacilli isolated from urine of symptomatic patients (1- 70 years) including males and females from indoor and outdoor patients by using double disc diffusion technique. Prevalence of extended-spectrum beta-lactamases production was seen in 71 (61.2%) enteric gram-negative organisms, the most prevalent gram-negative organism was Klebsiella pneumoniae 40 (71.4%) followed by Escherichia coli 27 (62.8%) and Pseudomonas aeruginosa 3 (25%). The extended-spectrum beta-lactamases producers were more prevalent in indoor patients 63 (88.7%) compared to outdoor patients 8 (11.3%), more in females 43 (60.6%) than males, 28 (39.4%). The extended-spectrum beta-lactamases producing gram-negative rods had more antibiotic-resistant profile than non-producers. All enteric gram negative rods should be tested for the production of extended-spectrum beta-lactamases in routine microbiology laboratory. (author)

Impact of removing mucosal barrier injury laboratory-confirmed bloodstream infections from central line-associated bloodstream infection rates in the National Healthcare Safety Network, 2014.

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See, Isaac; Soe, Minn M; Epstein, Lauren; Edwards, Jonathan R; Magill, Shelley S; Thompson, Nicola D

2017-03-01

Central line-associated bloodstream infection (CLABSI) event data reported to the National Healthcare Safety Network from 2014, the first year of required use of the mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI) definition, were analyzed to assess the impact of removing MBI-LCBI events from CLABSI rates. CLABSI rates decreased significantly in some location types after removing MBI-LCBI events, and MBI-LCBI events will be removed from publicly reported CLABSI rates. Published by Elsevier Inc.

Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

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Singh, Nina; Wagener, Marilyn M; Obman, Asia; Cacciarelli, Thomas V; de Vera, Michael E; Gayowski, Timothy

2004-07-01

During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.

The changing epidemiology of Staphylococcus aureus bloodstream infection

DEFF Research Database (Denmark)

Laupland, K.B.; Lyytikäinen, O.; Søgaard, Mette

2013-01-01

Clin Microbiol Infect ABSTRACT: Although the epidemiology of Staphylococcus aureus bloodstream infection (BSI) has been changing, international comparisons are lacking. We sought to determine the incidence of S. aureus BSI and assess trends over time and by region. Population-based surveillance w...

Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle

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Gniadek, Thomas J.; Carroll, Karen C.

2016-01-01

The non-glucose-fermenting Gram-negative bacilli Pseudomonas aeruginosa and Acinetobacter baumannii are increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF. PMID:26912753

Emerging trends of bloodstream infection: A six-year study at a paediatric tertiary care hospital in kabul

International Nuclear Information System (INIS)

Tariq, T.M.; Rasool, E.

2016-01-01

To determine the frequency of pathogens causing bloodstream infections and evaluate their trends and antibiogram patterns among in-patients in a paediatric tertiary care centre. Study Design: Descriptive study. Place and Duration of Study: French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan in two phases, from January 2010 to December 2015. Methodology: Results of blood cultures from suspected cases of sepsis admitted in the FMIC, from January 2010 to December 2012 (Period-1), and from January 2013 to December 2015 (Period-2) were completed. Standard microbiological methods were followed for blood culture and antibiotic sensitivity testing. Results: Out of total 1,040 cases of culture proven sepsis, 528 (50.77%) Gram-negative bacilli (GNB), 474 (45.58%) Gram-positive cocci (GPC), and 38 (3.65%) Candida species were isolated during the entire study period. Out of 528 GNB isolates, 373 (70.64%) belonged to the Enterobacteriaceae and 155 (29.36%) were non-fermenters. Among Enterobacteriaceae, 168 (31.82%) were Klebsiella species (K. pneumoniae=124, K. oxytoca=44), 70 (13.26%) were Enterobacter species (E. cloacae=52, E. aerogenes=18), 65 (12.31%) were E. coli, 37 (7.01%) were Serratia marcescens and 31 (5.87%) were others. Out of 155 non-fermenters, 88 (16.67%) were Pseudomonas aeruginosa, 39 (7.39%) were Burkholderia cepacia and 18 (3.41%) were Stenotrophomonas maltophilia. There was a drop in the frequency of Enterobacteriaceae from 85% in Period-1 to 58.68% in Period-2. There was an increase in the frequency of nonuniformities from 15% to 41.32%, particularly 18 new cases of sepsis caused by Stenotrophomonas maltophilia during Period-2. Among GPC, there was an overall rise of 16.14% in the prevalence of Staphylococcus epidermidis during Period-2 and a drop of 9.64% in the frequency of Staphylococcus aureus during Period-2. The majority of Gram-negative isolates were multidrug-resistant to commonly used antibiotics. However, most of the

Epidemiology of infections caused by multiresistant gram-negatives: ESBLs, MBLs, panresistant strains.

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Rossolini, Gian Maria; Mantengoli, Elisabetta; Docquier, Jean-Denis; Musmanno, Rosa Anna; Coratza, Grazietta

2007-07-01

Microbial drug resistance is a growing problem of global magnitude. In gram-negative pathogens, the most important resistance problems are encountered in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter, with increasing trends observed for all major anti-gram-negative agents (beta-lactams, fluoroquinolones and aminoglycosides). A matter of major concern is the emergence of new beta-lactamases capable of degrading the expanded-spectrum cephalosporins and/or carbapenems, such as the extended-spectrum beta-lactamases (ESBLs) and the carbapenemases. These beta-lactamase genes are often associated with resistance determinants to non-beta-lactam agents (e.g. aminoglycosides and fluoroquinolones), and strains producing ESBLs or carbapenemases often exhibit complex multidrug resistant phenotypes and sometimes are panresistant. The problem is worsened by the dearth of new agents active on multidrug-resistant Gram-negatives in the pipeline. The importance to develop better strategies to control resistance is underscored.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

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Lanini, Simone; Costa, Alessandro Nanni; Puro, Vincenzo; Procaccio, Francesco; Grossi, Paolo Antonio; Vespasiano, Francesca; Ricci, Andrea; Vesconi, Sergio; Ison, Michael G; Carmeli, Yehuda; Ippolito, Giuseppe

2015-01-01

Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

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Simone Lanini

Full Text Available Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients.Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively. Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days. Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%. Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not.The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant

Will new antimicrobials overcome resistance among Gram-negatives?

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Bassetti, Matteo; Ginocchio, Francesca; Mikulska, Małgorzata; Taramasso, Lucia; Giacobbe, Daniele Roberto

2011-10-01

The spread of resistance among Gram-positive and Gram-negative bacteria represents a growing challenge for the development of new antimicrobials. The pace of antibiotic drug development has slowed during the last decade and, especially for Gram-negatives, clinicians are facing a dramatic shortage in the availability of therapeutic options to face the emergency of the resistance problem throughout the world. In this alarming scenario, although there is a shortage of compounds reaching the market in the near future, antibiotic discovery remains one of the keys to successfully stem and maybe overcome the tide of resistance. Analogs of already known compounds and new agents belonging to completely new classes of antimicrobials are in early stages of development. Novel and promising anti-Gram-negative antimicrobials belong both to old (cephalosporins, carbapenems, β-lactamase inhibitors, monobactams, aminoglycosides, polymyxin analogues and tetracycline) and completely new antibacterial classes (boron-containing antibacterial protein synthesis inhibitors, bis-indoles, outer membrane synthesis inhibitors, antibiotics targeting novel sites of the 50S ribosomal subunit and antimicrobial peptides). However, all of these compounds are still far from being introduced into clinical practice. Therefore, infection control policies and optimization in the use of already existing molecules are still the most effective approaches to reduce the spread of resistance and preserve the activity of antimicrobials.

[Uncommon non-fermenting Gram-negative rods as pathogens of lower respiratory tract infection].

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Juhász, Emese; Iván, Miklós; Pongrácz, Júlia; Kristóf, Katalin

2018-01-01

Glucose non-fermenting Gram-negative bacteria are ubiquitous environmental organisms. Most of them are identified as opportunistic, nosocomial pathogens in patients. Uncommon species are identified accurately, mainly due to the introduction of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology practice. Most of these uncommon non-fermenting rods are isolated from lower respiratory tract samples. Their significance in lower respiratory tract infections, such as rules of their testing are not clarified yet. The aim of this study was to review the clinical microbiological features of these bacteria, especially their roles in lower respiratory tract infections and antibiotic treatment options. Lower respiratory tract samples of 3589 patients collected in a four-year period (2013-2016) were analyzed retrospectively at Semmelweis University (Budapest, Hungary). Identification of bacteria was performed by MALDI-TOF MS, the antibiotic susceptibility was tested by disk diffusion method. Stenotrophomonas maltophilia was revealed to be the second, whereas Acinetobacter baumannii the third most common non-fermenting rod in lower respiratory tract samples, behind the most common Pseudomonas aeruginosa. The total number of uncommon non-fermenting Gram-negative isolates was 742. Twenty-three percent of isolates were Achromobacter xylosoxidans. Beside Chryseobacterium, Rhizobium, Delftia, Elizabethkingia, Ralstonia and Ochrobactrum species, and few other uncommon species were identified among our isolates. The accurate identification of this species is obligatory, while most of them show intrinsic resistance to aminoglycosides. Resistance to ceftazidime, cefepime, piperacillin-tazobactam and carbapenems was frequently observed also. Ciprofloxacin, levofloxacin and trimethoprim-sulfamethoxazole were found to be the most effective antibiotic agents. Orv Hetil. 2018; 159(1): 23-30.

ESRD QIP - NHSN Bloodstream Infection - Payment Year 2018

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U.S. Department of Health & Human Services — This dataset includes facility details, performance ratio, measure score, and the state and national average measure scores for the NHSN bloodstream infection...

Association between preterm labor and genitourinary tract infections caused by Trichomonas vaginalis, Mycoplasma hominis, Gram-negative bacilli, and coryneforms

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Alaa El-Dien M.S. Hosny

2017-09-01

Conclusion: Our study demonstrated that the main risk factors for PTL were vaginal infection with T. vaginalis, M. hominis, coryneforms, and Gram-negative bacilli, and their determinants (vaginal pH>5, positive whiff test, heavy vaginal bleeding. Both young age (< 20 years and poor obstetric history were also the risk factors. Therefore, screening for genitourinary tract infections is strongly recommended to be included in prenatal care.

The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila.

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Duneau, David F; Kondolf, Hannah C; Im, Joo Hyun; Ortiz, Gerardo A; Chow, Christopher; Fox, Michael A; Eugénio, Ana T; Revah, J; Buchon, Nicolas; Lazzaro, Brian P

2017-12-21

Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection. We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria. We found that both virgin and mated females are more susceptible than mated males to most, but not all, infections. We investigated in more detail the lower resistance of females to infection with Providencia rettgeri, a Gram-negative bacterium that naturally infects D. melanogaster. We found that females have a higher number of phagocytes than males and that ablation of hemocytes does not eliminate the dimorphism in resistance to P. rettgeri, so the observed dimorphism does not stem from differences in the cellular response. The Imd pathway is critical for the production of antimicrobial peptides in response to Gram-negative bacteria, but mutants for Imd signaling continued to exhibit dimorphism even though both sexes showed strongly reduced resistance. Instead, we found that the Toll pathway is responsible for the dimorphism in resistance. The Toll pathway is dimorphic in genome-wide constitutive gene expression and in induced response to infection. Toll signaling is dimorphic in both constitutive signaling and in induced activation in response to P. rettgeri infection. The dimorphism in pathway activation can be specifically attributed to Persephone-mediated immune stimulation, by which the Toll pathway is triggered in response to pathogen-derived virulence factors. We additionally found that, in absence of Toll signaling, males become more susceptible than females to the Gram-positive Enterococcus faecalis. This reversal in susceptibility between male and female Toll

Gram-negative, but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes.

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Hessle, Christina C; Andersson, Bengt; Wold, Agnes E

2003-12-01

Gram-positive and Gram-negative bacteria induce different cytokine patterns in human mononuclear cells. We have seen that Gram-positives preferentially induce IL-12 and TNF-alpha, whereas Gram-negatives induce more IL-10, IL-6, and IL-8. In this study, we compared the capacity of these two groups of bacteria to induce PGE2. Monocytes stimulated with Gram-negative bacterial species induced much more PGE2 than did Gram-positive bacteria (5600 +/- 330 vs. 1700 +/- 670 pg/mL, p Gram-positive and Gram-negative bacteria. We suggest that Gram-positive and Gram-negative bacteria may stimulate different innate effector functions; Gram-positive bacteria promoting cell-mediated effector functions whereas Gram-negative bacteria inducing mediators inhibiting the same.

Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact.

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Mukerji, Shewli; O'Dea, Mark; Barton, Mary; Kirkwood, Roy; Lee, Terence; Abraham, Sam

2017-02-28

Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015.

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Karlowsky, James A; Hoban, Daryl J; Hackel, Meredith A; Lob, Sibylle H; Sahm, Daniel F

Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (%) for K. pneumoniae (92.2, 92.3), Enterobacter spp. (97.5, 92.1), and P. aeruginosa (85.3, 75.2) isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6) and imipenem (79.2, 75.9) showed substantially higher rates of susceptibility (%) than other β-lactams, including piperacillin-tazobactam (35.9, 37.4) against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013–2015

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James A. Karlowsky

2017-05-01

Full Text Available Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI and 970 isolates from urinary tract infections (UTI were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (% for K. pneumoniae (92.2, 92.3, Enterobacter spp. (97.5, 92.1, and P. aeruginosa (85.3, 75.2 isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6 and imipenem (79.2, 75.9 showed substantially higher rates of susceptibility (% than other β-lactams, including piperacillin-tazobactam (35.9, 37.4 against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed.

Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

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Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

2013-01-01

Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID

Glycosaminoglycans are involved in pathogen adherence to corneal epithelial cells differently for Gram-positive and Gram-negative bacteria

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Beatriz García

2016-11-01

Full Text Available The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies.

Molecular epidemiology of carbapenem resistant gram-negative bacilli from infected pediatric population in tertiary - care hospitals in Medellín, Colombia: an increasing problem.

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Vanegas, Johanna M; Parra, O Lorena; Jiménez, J Natalia

2016-09-01

Gram-negative bacilli are a cause of serious infections in the pediatric population. Carbapenem are the treatment of choice for infections caused by multidrug-resistant Gram-negative bacilli, but the emergence of carbapenem resistance has substantially reduced access to effective antimicrobial regimens. Children are a population vulnerable to bacterial infections and the emergence of resistance can worsen prognosis. The aim of this study is to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant Gram-negative bacilli in pediatric patients from five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to June 2014. All pediatric patients infected by carbapenem-resistant Gram-negative bacilli were included. Clinical information for each patient was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP bla NDM, bla OXA-48 and bla KPC genes and PFGE and MLST for molecular typing. A total of 59 patients were enrolled, most of them less than 1 year old (40.7 % n = 24), with a previous history of antibiotic use (94.9 %; n = 56) and healthcare-associated infections - predominately urinary tract infections (31.0 %; n = 18). Klebsiella pneumoniae was the most frequent bacteria (47.4 %), followed by Enterobacter cloacae (40.7 %) and Pseudomonas aeruginosa (11.9 %). For K. pneumoniae, KPC was the predominant resistance mechanism (85.7 %; n = 24) and ST14 was the most common clone (39.3 % n = 11), which included strains closely related by PFGE. In contrast, E. cloacae and P. aeruginosa were prevailing non-carbapenemase-producing isolates (only KPC and VIM were detected in 1 and 3 isolates, respectively) and high genetic diversity according to PFGE and MLST was found in the majority of the cases. In recent years, increasing carbapenem-resistant bacilli in children has become in a matter

Veillonella, Firmicutes: Microbes disguised as Gram negatives

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Vesth, Tammi Camilla; Ozen, Asli; Andersen, Sandra Christine

2013-01-01

Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared......, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely...... related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the (mainly) Gram positive phylum of the Firmicutes. Further studies are required to unveil the evolutionary history...

Restriction of cephalosporins and control of extended spectrum beta-lactamase producing gram negative bacteria in a neonatal intensive care unit.

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Murki, Srinivas; Jonnala, Sravanthi; Mohammed, Faheemuddin; Reddy, Anupama

2010-09-01

This interventional study with historical controls was conducted to study the effect of cephalosporin restriction on the incidence of extended spectrum beta-lactamase (ESBL) gram negative infections in neonates admitted to intensive care unit. All gram negative isolates from the blood were evaluated for beta lactamase production. The incidence of ESBL production was compared before (year 2007) and after cephalosporin restriction (year 2008). Thirty two neonates (3% of NICU admissions) in the year 2007 and fifty six (5.2%) in the year 2008, had gram negative septicemia. The incidence of ESBL gram negatives decreased by 22% (47% to 25%, P=0.03). Restriction of all class of cephalosporins significantly decreased the incidence of ESBL gram negative infections.

Efficacy of an infection control programme in reducing nosocomial bloodstream infections in a Senegalese neonatal unit.

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Landre-Peigne, C; Ka, A S; Peigne, V; Bougere, J; Seye, M N; Imbert, P

2011-10-01

Neonatal nosocomial infections are public health threats in the developing world, and successful interventions are rarely reported. A before-and-after study was conducted in the neonatal unit of the Hôpital Principal de Dakar, Senegal to assess the efficacy of a multi-faceted hospital infection control programme implemented from March to May 2005. The interventions included clustering of nursing care, a simple algorithm for empirical therapy of suspected early-onset sepsis, minimal invasive care and promotion of early discharge of neonates. Data on nosocomial bloodstream infections, mortality, bacterial resistance and antibiotic use were collected before and after implementation of the infection control programme. One hundred and twenty-five infants were admitted immediately before the programme (Period 1, January-February 2005) and 148 infants were admitted immediately after the programme (Period 2, June-July 2005). The two groups of infants were comparable in terms of reason for admission and birth weight. After implementation of the infection control programme, the overall rate of nosocomial bloodstream infections decreased from 8.8% to 2.0% (P=0.01), and the rate of nosocomial bloodstream infections/patient-day decreased from 10.9 to 2.9/1000 patient-days (P=0.03). Overall mortality rates did not differ significantly. The proportion of neonates who received antimicrobial therapy for suspected early-onset sepsis decreased significantly from 100% to 51% of at-risk infants (Punit, simple, low-cost and sustainable interventions led to the control of a high incidence of bacterial nosocomial bloodstream infections, and the efficacy of these interventions was long-lasting. Such interventions could be extended to other low-income countries. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Antiseptic and antibiotic resistance in Gram-negative bacteria causing urinary tract infection.

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Stickler, D J; Thomas, B

1980-01-01

A collection of 802 isolates of Gram-negative bacteria causing urinary tract infections was made from general practice, antenatal clinics, and local hospitals. The organisms were tested for their sensitivity to chlorhexidine, cetrimide, glutaraldehyde, phenyl mercuric nitrate, a phenolic formulation, and a proprietary antiseptic containing a mixture of picloxydine, octyl phenoxy polyethoxyethanol, and benzalkonium chloride. Escherichia coli, the major species isolated, proved to be uniformly sensitive to these agents. Approximately 10% of the total number of isolates, however, exhibited a degree of resistance to the cationic agents. These resistant organisms were members of the genera Proteus, Providencia, and Pseudomonas; they were also generally resistant to five, six, or seven antibiotics. It is proposed therefore that an antiseptic policy which involves the intensive use of cationic antiseptics might lead to the selection of a flora of notoriously drug-resistant species. PMID:6769972

Rapid and cost-effective identification and antimicrobial susceptibility testing in patients with Gram-negative bacteremia directly from blood-culture fluid.

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Sakarikou, Christina; Altieri, Anna; Bossa, Maria Cristina; Minelli, Silvia; Dolfa, Camilla; Piperno, Micol; Favalli, Cartesio

2018-03-01

Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) in bacteremia cases or sepsis could improve patient prognosis. Thus, it is important to provide timely reports, which make it possible for clinicians to set up appropriate antibiotic therapy during the early stages of bloodstream infection (BSI). This study evaluates an in-house microbiological protocol for early ID as well as AST on Gram negative bacteria directly from positive monomicrobial and polymicrobial blood cultures (BCs). A total of 102 non-duplicated positive BCs from patients with Gram-negative bacteremia were tested. Both IDs and ASTs were performed from bacterial pellets extracted directly from BCs using our protocol, which was applied through the combined use of a MALDI-TOF MS and Vitek2 automated system. The results of our study showed a 100% agreement in bacterial ID and 98.25% categorical agreement in AST when compared to those obtained by routine conventional methods. We recorded only a 0.76% minor error (mE), 0.76% major error (ME) and a 0.20% very major error (VME). Moreover, the turnaround time (TAT) regarding the final AST report was significantly shortened (ΔTAT = 8-20 h, p patient management, by early and appropriate antimicrobial treatment and could potentially optimize antimicrobial stewardship programs. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk of vancomycin-resistant enterococci bloodstream infection among patients colonized with vancomycin-resistant enterococci

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Ahu Kara

2015-01-01

Conclusion: In conclusion, our study found that 1.55% of vancomycin-resistant enterococci-colonized children had developed vancomycin-resistant enterococci bloodstream infection among the pediatric intensive care unit and hematology/oncology patients; according to our findings, we suggest that immunosupression is the key point for developing vancomycin-resistant enterococci bloodstream infections.

Investigational drugs for the treatment of infections caused by multidrug-resistant Gram-negative bacteria.

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Avery, Lindsay M; Nicolau, David P

2018-04-01

Infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) are associated with significant mortality and costs. New drugs in development to combat these difficult-to-treat infections primarily target carbapenem-resistant Enterobacteriaceae, MDR Pseudomonas aeruginosa, and MDR Acinetobacter baumannii. Areas covered: The authors summarize in vitro and in vivo efficacy studies, as well as available clinical trial findings, for new agents in development for treatment of infection caused by MDR-GNB. Information regarding dosage regimens utilized in clinical trials and key pharmacokinetic and pharmacodynamic considerations are provided if available. A summary of recently approved agents, delafloxacin and meropenem/vaborbactam, is also included. Expert opinion: The development of multiple novel agents to fight MDR-GNB is promising to help save the lives of patients who acquire infection, and judicious use of these agents is imperative once they come to market to prevent the development of resistance. The other component paramount to this field of research is implementation of effective infection control policies and carbapenem-resistant Enterobacteriaceae (CRE) carrier screening protocols to mitigate the worldwide spread of MDR-GNB. Further investigation of anti-infective synergistic combinations will also be important, as well as support for economic research to reveal the true cost-benefit of utilization of the new agents discussed herein.

[Catheter-associated bloodstream infections: implementation of a new consensus protocol].

Science.gov (United States)

Urrea Ayala, M; Rozas Quesada, L

2009-07-01

Catheter-associated bloodstream infection is highly prevalent and often associated with fatal complications. Some studies have shown that applying preventive interventions could help to reduce and control this type of infection. To determine whether a new consensus protocol for the manipulation and maintenance of central venous catheters would decrease catheter-associated bloodstream infections (CA-BSIs) in paediatric patients. To evaluate its compliance in intensive care units. Prospective study in the paediatric (PICU) and neonatal (NICU) intensive cares units, haematology, oncology and hospital wards in a Maternal and Paediatric reference Hospital in Barcelona. The study period is divided into two periods: before (first semester) and after the start of the new protocol (second semester) in 2007. The most important changes have been the insertion of the hermetic connection in the proximal and distal site (between the line and the syringe) of the central venous catheter (CVC), the labelling of the medication line and the CVC with the date of placement. A check-list to evaluate compliance was introduced in both intensive care units (paediatrics and neonatal) during the second study period. The rates of bloodstream infection per 1000 catheter-days were assessed. The rate of bloodstream infections per 1000 catheter-days before and after the start of the new protocol was 5.7 and 4.9 in PICU; 24.6 and 18.0 in NICU; 7.6 and 4.6 in haematology-oncology, and 11.9 and 10.3 in hospital wards. As regards compliance to the protocol, we found that proximal sealed connectors were used in more than 95% of the cases and up to 85% of the central venous catheter were labelled with the insertion date in both intensive care units. A consensus protocol for the use and maintenance of central venous catheters and healthcare worker training helped to control the rate of CA-BSIs. We reaffirm the importance of epidemiological surveillance as a measure for controlling nosocomial infections.

The Causes of Post-Operative Meningitis: The Comparison Of Gram-Negative and Gram-Positive Pathogens.

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Kurtaran, Behice; Kuscu, Ferit; Ulu, Aslihan; Inal, Ayse Seza; Komur, Suheyla; Kibar, Filiz; Cetinalp, Nuri Eralp; Ozsoy, Kerem Mazhar; Arslan, Yusuf Kemal; Aksu, Hasan Salih; Tasova, Yesim

2017-06-20

In this study, we aim to determine the microbiological etiology in critically ill neurosurgical patients with nosocomial meningitis (NM) and show the impact of Gram-negative rods and differences of patient's characteristics, clinical and prognostic measures between Gram-negative and Gram-positive meningitis. In this prospective, one center study we reviewed all adult patients hospitalized during a 12-year period and identified pathogens isolated from post-neurosurgical cases of NM. Demographic, clinical, and treatment characteristics were noted from the medical records. Of the 134 bacterial NM patients, 78 were male and 56 were female, with a mean age of 46±15.9 and median age of 50 (18-80) years. 141 strains isolated; 82 (58.2%) were Gram negative, 59 (41.8%) were Gram positive. Most common isolated microorganism was Acinetobacter baumannii (%34.8). In comparison of mortality data shows that the patients who have meningitis with Gram-negative pathogens have higher mortality than with Gram positives (p=0.034). The duration between surgery and meningitis was shorter in Gram negative meningitis cases compared to others (p=0.045) but the duration between the diagnosis and death was shorter in Gram-positive meningitis cases compared to Gram negatives (p= 0.017). CSF protein and lactate level were higher and glucose level was lower in cases of NM with Gram negatives (p value were respectively, 0.022, 0.039 and 0.049). As conclusions; in NM, Gram-negative pathogens were seen more frequently; A.baumanni was the predominant pathogen; and NM caused by Gram negatives had worse clinical and laboratory characteristic and prognostic outcome than Gram positives.

Different Use of Cell Surface Glycosaminoglycans As Adherence Receptors to Corneal Cells by Gram Positive and Gram Negative Pathogens

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García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F.; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M.

2016-01-01

The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies. PMID:27965938

Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria.

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Arzanlou, Mohsen; Chai, Wern Chern; Venter, Henrietta

2017-02-28

Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Specific Clinical Profile and Risk Factors for Mortality in General Surgery Patients with Infections by Multi-Drug-Resistant Gram-Negative Bacteria.

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Rubio-Perez, Ines; Martin-Perez, Elena; Domingo-García, Diego; Garcia-Olmo, Damian

2017-07-01

The incidence of gram-negative multi-drug-resistant (MDR) infections is increasing worldwide. This study sought to determine the incidence, clinical profiles, risk factors, and mortality of these infections in general surgery patients. All general surgery patients with a clinical infection by gram-negative MDR bacteria were studied prospectively for a period of five years (2007-2011). Clinical, surgical, and microbiologic parameters were recorded, with a focus on the identification of risk factors for MDR infection and mortality. Incidence of MDR infections increased (5.6% to 15.2%) during the study period; 106 patients were included, 69.8% presented nosocomial infections. Mean age was 65 ± 15 years, 61% male. Extended-spectrum β-lactamases (ESBL) Escherichia coli was the most frequent MDR bacteria. Surgical site infections and abscesses were the most common culture locations. The patients presented multiple pre-admission risk factors and invasive measures during hospitalization. Mortality was 15%, and related to older age (odds ratio [OR] 1.07), malnutrition (OR 13.5), chronic digestive conditions (OR 4.7), chronic obstructive pulmonary disease (OR 3.9), and surgical re-intervention (OR 9.2). Multi-drug resistant infections in the surgical population are increasing. The most common clinical profile is a 65-year-old male, with previous comorbidities, who has undergone a surgical intervention, intensive care unit (ICU) admission, and invasive procedures and who has acquired the MDR infection in the nosocomial setting.

Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness.

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Skovbjerg, Susann; Martner, Anna; Hynsjö, Lars; Hessle, Christina; Olsen, Ingar; Dewhirst, Floyd E; Tham, Wilhelm; Wold, Agnes E

2010-01-01

Upon bacterial stimulation, tissue macrophages produce a variety of cytokines that orchestrate the immune response that clears the infection. We have shown that Gram-positives induce higher levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMCs) than do Gram-negatives, which instead induce more of IL-6, IL-8, and IL-10. Here, we study whether these patterns follows or crosses taxonomic borders. PBMCs from blood donors were incubated with UV-inactivated bacteria representing 37 species from five phyla. IL-12, TNF, IL-1beta, IL-6, IL-8, and IL-10 were measured in the supernatants after 24 h and IFN-gamma after 5 days. Irrespective of phylogenetic position, Gram-positive bacteria induced much more IL-12 (nine times more on average) and IFN-gamma (seven times), more TNF (three times), and slightly more IL-1beta (1.5 times) than did Gram-negatives, which instead induced more IL-6 (1.5 times), IL-8 (1.9 times), and IL-10 (3.3 times) than did Gram-positives. A notable exception was the Gram-positive Listeria monocytogenes, which induced very little IL-12, IFN-gamma, and TNF. The results confirm the fundamental difference in innate immune responses to Gram-positive and Gram-negative bacteria, which crosses taxonomic borders and probably reflects differences in cell wall structure.

Prevalence of AmpC β-lactamase among Gram-negative bacteria ...

African Journals Online (AJOL)

Purpose: Infections caused by AmpC-positive bacteria results in high patient morbidity and mortality making their detection clinically important as they cannot be detected in routine susceptibility testing. This study aim to determine the prevalence of AmpC β-lactamase among Gram negative bacteria recovered from clinical ...

Breaking barriers: expansion of the use of endolysins as novel antibacterials against Gram-negative bacteria.

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Briers, Yves; Lavigne, Rob

2015-01-01

The emergence and spread of antibiotic-resistant bacteria drives the search for novel classes of antibiotics to replenish our armamentarium against bacterial infections. This is particularly critical for Gram-negative pathogens, which are intrinsically resistant to many existing classes of antibiotics due to the presence of a protective outer membrane. In addition, the antibiotics development pipeline is mainly oriented to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus. A promising novel class of antibacterials is endolysins. These enzymes encoded by bacterial viruses hydrolyze the peptidoglycan layer with high efficiency, resulting in abrupt osmotic lysis and cell death. Their potential as novel antibacterials to treat Gram-positive bacteria has been extensively demonstrated; however, the Gram-negative outer membrane has presented a formidable barrier for the use of endolysins against Gram-negatives until recently. This review reports on the most recent advances in the development of endolysins to kill Gram-negative species with a special focus on endolysin-engineered Artilysins(®).

Gram-negative prosthetic joint infection: outcome of a debridement, antibiotics and implant retention approach. A large multicentre study.

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Rodríguez-Pardo, D; Pigrau, C; Lora-Tamayo, J; Soriano, A; del Toro, M D; Cobo, J; Palomino, J; Euba, G; Riera, M; Sánchez-Somolinos, M; Benito, N; Fernández-Sampedro, M; Sorli, L; Guio, L; Iribarren, J A; Baraia-Etxaburu, J M; Ramos, A; Bahamonde, A; Flores-Sánchez, X; Corona, P S; Ariza, J

2014-11-01

We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement>30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68-81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13-0.40; pInfection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

[Clinical features of invasive candidiasis and risk factors for Candida bloodstream infection in children: a multicenter study in Urumqi, China].

Science.gov (United States)

Ai Er Ken, Ai Bi Bai; Ma, Zhi-Hua; Xiong, Dai-Qin; Xu, Pei-Ru

2017-04-01

To investigate the clinical features of invasive candidiasis in children and the risk factors for Candida bloodstream infection. A retrospective study was performed on 134 children with invasive candidiasis and hospitalized in 5 tertiary hospitals in Urumqi, China, between January 2010 and December 2015. The Candida species distribution was investigated. The clinical data were compared between the patients with and without Candida bloodstream infection. The risk factors for Candida bloodstream infection were investigated using multivariate logistic regression analysis. A total of 134 Candida strains were isolated from 134 children with invasive candidiasis, and non-albicans Candida (NAC) accounted for 53.0%. The incidence of invasive candidiasis in the PICU and other pediatric wards were 41.8% and 48.5% respectively. Sixty-eight patients (50.7%) had Candida bloodstream infection, and 45 patients (33.6%) had Candida urinary tract infection. There were significant differences in age, rate of use of broad-spectrum antibiotics, and incidence rates of chronic renal insufficiency, heart failure, urinary catheterization, and NAC infection between the patients with and without Candida bloodstream infection (Pcandidiasis is similar between the PICU and other pediatric wards. NAC is the most common species of invasive candidiasis. Candida bloodstream infection is the most common invasive infection. Younger age (1-24 months) and NAC infection are the risk factors for Candida bloodstream infection.

Neonatal bloodstream infections in a pediatric hospital in Vietnam

DEFF Research Database (Denmark)

Kruse, Alexandra Yasmin; Thieu Chuong, Do Huu; Phuong, Cam Ngoc

2013-01-01

Septicemia and bloodstream infections (BSIs) are major causes of neonatal morbidity and mortality in developing countries. We prospectively recorded all positive blood cultures (BSI) among neonates admitted consecutively to a tertiary pediatric hospital in Vietnam during a 12-month period. Among...

Prevention of bloodstream infections by photodynamic inactivation of multiresistant Pseudomonas aeruginosa in burn wounds

Science.gov (United States)

Hashimoto, M. C. E.; Prates, R. A.; Toffoli, D. J.; Courrol, L. C.; Ribeiro, M. S.

2010-02-01

Bloodstream infections are potentially life-threatening diseases. They can cause serious secondary infections, and may result in endocarditis, severe sepsis or toxic-shock syndrome. Pseudomonas aeruginosa is an opportunistic pathogen and one of the most important etiological factors responsible for nosocomial infections, mainly in immuno-compromissed hosts, characteristic of patients with severe burns. Its multiresistance to antibiotics produces many therapeutic problems, and for this reason, the development of an alternative method to antibiotic therapy is needed. Photodynamic inactivation (PDI) may be an effective and alternative therapeutic option to prevent bloodstream infections in patients with severe burns. In this study we report the use of PDI to prevent bloodstream infections in mice with third-degree burns. Burns were produced on the back of the animals and they were infected with 109 cfu/mL of multi-resistant (MR) P. aeruginosa. Fifteen animals were divided into 3 groups: control, PDT blue and PDT red. PDT was performed thirty minutes after bacterial inoculation using 10μM HB:La+3 and a light-emitting diode (LED) emitting at λ=460nm+/-20nm and a LED emitting at λ=645 nm+/-10nm for 120s. Blood of mice were colected at 7h, 10h, 15h, 18h and 22h pos-infection (p.i.) for bacterial counting. Control group presented 1×104 cfu/mL in bloodstream at 7h p.i. increasing to 1×106 at 22h, while mice PDT-treated did not present any bacteria at 7h; only at 22h p.i. they presented 1×104cfu/mL. These results suggest that HB:La+3 associated to blue LED or red LED is effective to delay and diminish MR P.aeruginosa bloodstream invasion in third-degree-burned mice.

Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria.

Science.gov (United States)

Pallett, Ann; Hand, Kieran

2010-11-01

Resistance in Gram-negative bacteria has been increasing, particularly over the last 6 years. This is mainly due to the spread of strains producing extended-spectrum β-lactamases (ESBLs) such as CTX-M enzymes or AmpC β-lactamases. Many of the isolates producing these enzymes are also resistant to trimethoprim, quinolones and aminoglycosides, often due to plasmid co-expression of other resistance mechanisms. CTX-M-producing Escherichia coli often occurs in the community and as E. coli is one of the commonest organisms causing urinary tract infections (UTIs) the choice of agents to treat these infections is diminishing. Novel combinations of antibiotics are being used in the community and broad-spectrum agents such as carbapenems are being used increasingly as empirical treatment for severe infections. Of particular concern therefore are reports in the UK of organisms that produce carbapenemases. As resistance is becoming more widespread, prudent use of antimicrobials is imperative and, as asymptomatic bacteriuria is typically benign in the elderly, antibiotics should not be prescribed without clinical signs of UTI. The use of antibiotics as suppressive therapy or long-term prophylaxis may no longer be defensible.

Prevalence of bloodstream pathogens is higher in neonatal encephalopathy cases vs. controls using a novel panel of real-time PCR assays.

Science.gov (United States)

Tann, Cally J; Nkurunziza, Peter; Nakakeeto, Margaret; Oweka, James; Kurinczuk, Jennifer J; Were, Jackson; Nyombi, Natasha; Hughes, Peter; Willey, Barbara A; Elliott, Alison M; Robertson, Nicola J; Klein, Nigel; Harris, Kathryn A

2014-01-01

In neonatal encephalopathy (NE), infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda. Multiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV), herpes simplex virus(HSV) and P. falciparum) were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC) was performed for all cases and unwell controls. Prevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028) using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae). Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively). This real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting.

Prevalence of bloodstream pathogens is higher in neonatal encephalopathy cases vs. controls using a novel panel of real-time PCR assays.

Directory of Open Access Journals (Sweden)

Cally J Tann

Full Text Available In neonatal encephalopathy (NE, infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda.Multiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV, herpes simplex virus(HSV and P. falciparum were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC was performed for all cases and unwell controls.Prevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028 using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae. Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively.This real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting.

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

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Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

2010-02-01

Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

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Zelenitsky, Sheryl A; Ariano, Robert E

2010-08-01

Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Significant factors with regard to treatment failure were low ciprofloxacin AUC(24)/MIC (P AUC(24) (P = 0.01). AUC(24)/MIC (P = 0.012) and MIC (P = 0.019) were significant variables in multivariate analyses; however, only the former remained significant (P = 0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC(24)/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P = 0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC(24)/MIC >or=250 (P = 0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC(24)/MIC >or=250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or=250, rather than the conventional target of >or=125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range.

Resistance to oral antibiotics in 4569 Gram-negative rods isolated from urinary tract infection in children.

Science.gov (United States)

Calzi, Anna; Grignolo, Sara; Caviglia, Ilaria; Calevo, Maria Grazia; Losurdo, Giuseppe; Piaggio, Giorgio; Bandettini, Roberto; Castagnola, Elio

2016-09-01

To investigate antibiotic resistance among pathogens isolated from urines in a tertiary care children's hospital in Italy. Retrospective analysis of prospectively collected data on antibiotic susceptibility of Gram-negatives isolated from urines at the Istituto Giannina Gaslini, Genoa - Italy from 2007 to 2014. Antibiotic susceptibility was evaluated. By means of CLSI criteria from 2007 to 2010, while from 2011 EUCAST criteria were adopted. Data on susceptibility to amoxicillin-clavulanate, co-trimoxazole, cefuroxime, nitrofurantoin, fosfomycin and ciprofloxacin were evaluated for Escherichia coli, while for other Enterobacteriaceae data were collected for amoxicillin-clavulanate, co-trimoxazole and ciprofloxacin and for ciprofloxacin against Pseudomonas aeruginosa. Univariate and multivariable analyses were performed for risk factors associated with resistance. A total of 4596 Gram-negative strains were observed in 3364 patients. A significant increase in the proportion of resistant strains was observed for E.coli against amoxicillin-clavulanate, cefuroxime and ciprofloxacin and for others Enterobacteriaceae against co-trimoxazole and ciprofloxacin. Resistance to nitrofurantoin and fosfomycin was very infrequent in E.coli. Logistic regression analysis showed that repeated episode of urinary tract infections was a risk factor for E.coli resistance to amoxicillin-clavulanate, co-trimoxazole and cefuroxime, while admission in one of the Units usually managing children with urinary tract malformations was significantly associated to resistance to amoxicillin-clavulanate and cefuroxime. In conclusion the present study shows an increase in antibiotic resistance in pediatric bacteria isolated from urines in children, especially in presence of repeated episodes and/or urinary tract malformations. This resistance is worrisome for beta-lactams and cotrimoxazole, and start to increase also for fluoroquinolones while nitrofurantoin and fosfomycin still could represent useful

Epidemiological investigation of Candida species causing bloodstream infection in paediatric small bowel transplant recipients.

Science.gov (United States)

Suhr, Mallory J; Gomes-Neto, João Carlos; Banjara, Nabaraj; Florescu, Diana F; Mercer, David F; Iwen, Peter C; Hallen-Adams, Heather E

2017-06-01

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterise the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidaemia in seven paediatric patients. Candida species from the recipients' ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harboured at least one Candida species. Fungaemia were caused by Candida parapsilosis, Candida albicans, Candida glabrata, Candida orthopsilosis and Candida pelliculosa. All but three bloodstream isolates showed susceptibility to all the antifungals tested. One C. glabrata isolate showed multidrug resistance to itraconazole, amphotericin B and posaconazole and intermediate resistance to caspofungin. Results are congruent with both endogenous (C. albicans, C. glabrata) and exogenous (C. parapsilosis) infections; results also suggest two patients were infected by the same strain of C. parapsilosis. Continuing to work towards a better understanding of sources of infection-particularly the exogenous sources-would lead to targeted prevention strategies. © 2017 Blackwell Verlag GmbH.

Comparison of beta-lactam regimens for the treatment of gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics.

Science.gov (United States)

Burgess, David S; Frei, Christopher R

2005-11-01

This study utilized pharmacokinetics/pharmacodynamics to compare beta-lactam regimens for the empirical and definitive treatment of gram-negative pulmonary infections in the ICU. Susceptibility data were extracted from the 2002 Intensive Care Unit Surveillance System (ISS) and pharmacokinetic parameters were obtained from published human studies. Monte Carlo simulation was used to model the free percent time above the MIC (free %T > MIC) for 18 beta-lactam regimens against all gram-negative isolates, Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. The cumulative fraction of response (CFR) was determined for bacteriostatic and bactericidal targets (free %T > MIC): penicillins (> or = 30/50%), cephalosporins/monobactams (> or = 40/70%) and carbapenems (> or = 20/40%). The 2002 ISS database contained MICs for 2408 gram-negative isolates including 1430 Enterobacteriaceae, 799 P. aeruginosa, and 179 A. baumannii. Imipenem had the highest percentage susceptible for all gram-negatives, Enterobacteriaceae and A. baumannii, while piperacillin/tazobactam had the highest percentage susceptible for P. aeruginosa. For empirical therapy, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h demonstrated the highest CFR. For definitive therapy, imipenem 0.5 g every 6 h, ertapenem 1 g daily and cefepime 2 g every 8 h, cefepime 1 g every 8 h and cefepime 1 g every 12 h had the highest bactericidal CFR against Enterobacteriaceae; ceftazidime 2 g every 8 h, cefepime 2 g every 8 h, piperacillin/tazobactam 3.375 g every 4 h, ceftazidime 1 g every 8 h and aztreonam 1 g every 8 h against P. aeruginosa; and imipenem 0.5 g every 6 h, ticarcillin/clavulanate 3.1 g every 4 h, ceftazidime 2 g every 8 h, cefepime 2 g every 8 h and ticarcillin/clavulanate 3.1 g every 6 h against A. baumannii. Based on pharmacokinetics/pharmacodynamics, imipenem 0.5 g every 6 h, cefepime 2 g every 8 h and ceftazidime 2 g every 8 h should be the preferred beta

Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

Science.gov (United States)

Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

2015-01-01

Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

Risk factors for laboratory-confirmed bloodstream infection in neonates undergoing surgical procedures

Directory of Open Access Journals (Sweden)

Roberta Maia de Castro Romanelli

2014-07-01

Conclusions: Shortening time on parenteral nutrition whenever possible and preference for non-invasive ventilation in neonates undergoing surgery should be considered in the assistance of these patients, with the goal of reducing Healthcare Associated Infections, especially laboratory-confirmed bloodstream infection.

Antimicrobial Activity of Ephedra pachyclada Methanol Extract on Some Enteric Gram Negative Bacteria Which Causes Nosocomial Infections by Agar Dilution Method

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Amin Sadeghi Dosari

2016-10-01

Full Text Available Background Past history indicates that plants were served as an important source of medicine. Otherwise, in developing countries people use medicinal plants against infectious disease because they cannot afford expensive drugs. Due to increasing rate of drug-resistant diseases, there is an urgent need to detect novel antimicrobial compounds from medicinal plants. Objectives The aim of the present study was to determine Antimicrobial activity of Ephedra pachyclada methanol extract on some enteric Gram-negative bacteria which causes nosocomial infections by agar dilution method. Methods In this cross-sectional study, in order to examine the antimicrobial effects of Ephedra pachyclada extract on intestinal Gram-negative bacteria, we exposed them to 0/128, 0/25, 0/5, 1, 2, 4 and 8 mg/mL of the extract. Ephedra pachyclada was collected from Jiroft Heights and methanolic extract was prepared with maceration method, during which, 50 gr powder of Ephedra pachyclada was dissolved in 300 mL of 80% methanol. Results In this study, the antibacterial effects of Ephedra pachyclada extract on Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli (PTCC-O157, Escherichia coli (ATCC-25922, Klebsiella pnemoniae, Serratia marcescens was investigated, defining the minimum inhibitory concentration (MIC by agar dilution method. It has been demonstrated that methanolic extract of Ephedra pachyclada affect intestinal Gram-negative bacteria. Conclusions The result showed that, Ephedra pachyclada extract has effective antimicrobial ingredients which are cheap and readily available. It can be used for medicinal purposes in the production of antimicrobial drug.

Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China: SMART China 2011.

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Zhang, Hui; Yang, Qiwen; Xiao, Meng; Chen, Minjun; Badal, Robert E; Xu, Yingchun

2014-01-01

The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli (GNBs) from intra-abdominal infections (IAIs) in patients worldwide. In 2011, 1 929 aerobic and facultative GNBs from 21 hospitals in 16 cities in China were collected. All isolates were tested using a panel of 12 antimicrobial agents, and susceptibility was determined following the Clinical Laboratory Standards Institute guidelines. Among the Gram-negative pathogens causing IAIs, Escherichia coli (47.3%) was the most commonly isolated, followed by Klebsiella pneumoniae (17.2%), Pseudomonas aeruginosa (10.1%), and Acinetobacter baumannii (8.3%). Enterobacteriaceae comprised 78.8% (1521/1929) of the total isolates. Among the antimicrobial agents tested, ertapenem and imipenem were the most active agents against Enterobacteriaceae, with susceptibility rates of 95.1% and 94.4%, followed by amikacin (93.9%) and piperacillin/tazobactam (87.7%). Susceptibility rates of ceftriaxone, cefotaxime, ceftazidime, and cefepime against Enterobacteriaceae were 38.3%, 38.3%, 61.1%, and 50.8%, respectively. The leastactive agent against Enterobacteriaceae was ampicillin/sulbactam (25.9%). The extended-spectrum β-lactamase (ESBL) rates among E. coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis were 68.8%, 38.1%, 41.2%, and 57.7%, respectively. Enterobacteriaceae were the major pathogens causing IAIs, and the most active agents against the study isolates (including those producing ESBLs) were ertapenem, imipenem, and amikacin. Including the carbapenems, most agents exhibited reduced susceptibility against ESBL-positive and multidrug-resistant isolates.

Raman Spectroscopy of Xylitol Uptake and Metabolism in Gram-Positive and Gram-Negative Bacteria▿

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Palchaudhuri, Sunil; Rehse, Steven J.; Hamasha, Khozima; Syed, Talha; Kurtovic, Eldar; Kurtovic, Emir; Stenger, James

2011-01-01

Visible-wavelength Raman spectroscopy was used to investigate the uptake and metabolism of the five-carbon sugar alcohol xylitol by Gram-positive viridans group streptococcus and the two extensively used strains of Gram-negative Escherichia coli, E. coli C and E. coli K-12. E. coli C, but not E. coli K-12, contains a complete xylitol operon, and the viridans group streptococcus contains an incomplete xylitol operon used to metabolize the xylitol. Raman spectra from xylitol-exposed viridans group streptococcus exhibited significant changes that persisted even in progeny grown from the xylitol-exposed mother cells in a xylitol-free medium for 24 h. This behavior was not observed in the E. coli K-12. In both viridans group streptococcus and the E. coli C derivative HF4714, the metabolic intermediates are stably formed to create an anomaly in bacterial normal survival. The uptake of xylitol by Gram-positive and Gram-negative pathogens occurs even in the presence of other high-calorie sugars, and its stable integration within the bacterial cell wall may discontinue bacterial multiplication. This could be a contributing factor for the known efficacy of xylitol when taken as a prophylactic measure to prevent or reduce occurrences of persistent infection. Specifically, these bacteria are causative agents for several important diseases of children such as pneumonia, otitis media, meningitis, and dental caries. If properly explored, such an inexpensive and harmless sugar-alcohol, alone or used in conjunction with fluoride, would pave the way to an alternative preventive therapy for these childhood diseases when the causative pathogens have become resistant to modern medicines such as antibiotics and vaccine immunotherapy. PMID:21037297

Value of Public Health Funding in Preventing Hospital Bloodstream Infections in the United States.

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Whittington, Melanie D; Bradley, Cathy J; Atherly, Adam J; Campbell, Jonathan D; Lindrooth, Richard C

2017-11-01

To estimate the association of 1 activity of the Prevention and Public Health Fund with hospital bloodstream infections and calculate the return on investment (ROI). The activity was funded for 1 year (2013). A difference-in-differences specification evaluated hospital standardized infection ratios (SIRs) before funding allocation (years 2011 and 2012) and after funding allocation (years 2013 and 2014) in the 15 US states that received the funding compared with hospital SIRs in states that did not receive the funding. We estimated the association of the funded public health activity with SIRs for bloodstream infections. We calculated the ROI by dividing cost offsets from infections averted by the amount invested. The funding was associated with a 33% (P < .05) reduction in SIRs and an ROI of $1.10 to $11.20 per $1 invested in the year of funding allocation (2013). In 2014, after the funding stopped, significant reductions were no longer evident. This activity was associated with a reduction in bloodstream infections large enough to recoup the investment. Public health funding of carefully targeted areas may improve health and reduce health care costs.

Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.

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Poulakou, Garyphallia; Giamarellou, Helen

2008-05-01

Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. This drug evaluation focuses on the position of doripenem, a novel forthcoming carbapenem. Mechanisms of resistance and new drugs with anti-Gram-negative activity are also briefly reviewed. Literature search was performed for new carbapenems, new antibiotics, doripenem, metallo-beta-lactamase inhibitors, multidrug-resistant pathogens, antipseudomonal antibiotics and multidrug-resistant epidemiology. Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens. Against P. aeruginosa, doripenem exhibits rapid bactericidal activity with 2 - 4-fold lower MIC values, compared to meropenem. Exploitation of pharmacokinetic/pharmacodynamic applications could offer a treatment opportunity against strains exhibiting borderline resistance to doripenem. Stability against numerous beta-lactamases, low adverse event potential and more potent in vitro antibacterial activity against P. aeruginosa and A. baumanni compared to the existing carbapenems, are its principal features.

Impact of round-the-clock CSF Gram stain on empirical therapy for suspected central nervous system infections.

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Tissot, F; Prod'hom, G; Manuel, O; Greub, G

2015-09-01

The impact of round-the-clock cerebrospinal fluid (CSF) Gram stain on overnight empirical therapy for suspected central nervous system (CNS) infections was investigated. All consecutive overnight CSF Gram stains between 2006 and 2011 were included. The impact of a positive or a negative test on empirical therapy was evaluated and compared to other clinical and biological indications based on institutional guidelines. Bacterial CNS infection was documented in 51/241 suspected cases. Overnight CSF Gram stain was positive in 24/51. Upon validation, there were two false-positive and one false-negative results. The sensitivity and specificity were 41 and 99 %, respectively. All patients but one had other indications for empirical therapy than Gram stain alone. Upon obtaining the Gram result, empirical therapy was modified in 7/24, including the addition of an appropriate agent (1), addition of unnecessary agents (3) and simplification of unnecessary combination therapy (3/11). Among 74 cases with a negative CSF Gram stain and without formal indication for empirical therapy, antibiotics were withheld in only 29. Round-the-clock CSF Gram stain had a low impact on overnight empirical therapy for suspected CNS infections and was associated with several misinterpretation errors. Clinicians showed little confidence in CSF direct examination for simplifying or withholding therapy before definite microbiological results.

A molecular gram stain using broad range PCR and pyrosequencing technology: a potentially useful tool for diagnosing orthopaedic infections.

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Kobayashi, Naomi; Bauer, Thomas W; Togawa, Daisuke; Lieberman, Isador H; Sakai, Hiroshige; Fujishiro, Takaaki; Tuohy, Marion J; Procop, Gary W

2005-06-01

The bacteria associated with orthopaedic infections are usually common gram-positive and gram-negative bacteria. This fundamental grouping of bacteria is a necessary first step in the selection of appropriate antibiotics. Since polymerase chain reaction (PCR) is more rapid and may be more sensitive than culture, we developed a postamplification pyrosequencing method to subcategorize bacteria based on a few nucleotide polymorphisms in the 16S rRNA gene. We validated this method using well-characterized strains of bacteria and applied it to specimens from spinal surgery cases with suspected infections. Lysates of 114 bacteria including 75 species were created following standard cultivation to obtain DNA. The DNA was amplified by a broad-range real-time PCR. The amplicons were evaluated by pyrosequencing and were classified as gram-positive, gram-negative, or acid-fast bacilli based on the first three to five nucleotides sequenced. In addition, clinical cases of suspected infection were obtained from spinal surgery. The results of the "molecular Gram stain" were compared with the results of traditional Gram stain and culture. The lysates of 107 (93.9%) of the bacteria extracts tested were appropriately categorized as gram-positive and gram-negative or as acid-fast bacilli on the basis of this assay. The sensitivity and specificity of this assay were 100% and 97.4% for gram-positive and 88.3% and 100% for gram-negative isolates. All of the five clinical samples were appropriately categorized as containing gram-positive or gram-negative bacteria with this assay. This study demonstrates that high sensitivity and specificity of a molecular gram stain may be achieved using broad-range real-time PCR and pyrosequencing.

Organo-Selenium Coatings Inhibit Gram-Negative and Gram-Positive Bacterial Attachment to Ophthalmic Scleral Buckle Material.

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Tran, Phat; Arnett, Avery; Jarvis, Courtney; Mosley, Thomas; Tran, Khien; Hanes, Rob; Webster, Dan; Mitchell, Kelly; Dominguez, Leo; Hamood, Abdul; Reid, Ted W

2017-09-01

Biofilm formation is a problem for solid and sponge-type scleral buckles. This can lead to complications that require removal of the buckle, and result in vision loss due to related ocular morbidity, primarily infection, or recurrent retinal detachment. We investigate the ability of a covalent organo-selenium coating to inhibit biofilm formation on a scleral buckle. Sponge and solid Labtican brand scleral buckles were coated with organo-selenium coupled to a silyation reagent. Staphylococcus aureus biofilm formation was monitored by a standard colony-forming unit assay and the confocal laser scanning microscopy, while Pseudomonas aeruginosa biofilm formation was examined by scanning electron microscopy. Stability studies were done, by soaking in phosphate buffer saline (PBS) at room temperature for 2 months. Toxicity against human corneal epithelial cell was examined by growing the cells in the presence of organo-selenium-coated scleral buckles. The organo-selenium coating inhibited biofilm formation by gram-negative and gram-positive bacteria. The buckle coatings also were shown to be fully active after soaking in PBS for 2 months. The organo-selenium coatings had no effect on the viability of human corneal epithelial cells. Organo-selenium can be used to covalently coat a scleral buckle, which is stable and inhibits biofilm formation for gram-negative and gram-positive bacteria. The organo-selenium buckle coating was stable and nontoxic to cell culture. This technology provides a means to inhibit bacterial attachment to devices attached to the eye, without damage to ocular cells.

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

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Mularoni, A; Bertani, A; Vizzini, G; Gona, F; Campanella, M; Spada, M; Gruttadauria, S; Vitulo, P; Conaldi, P; Luca, A; Gridelli, B; Grossi, P

2015-10-01

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Gram positive and Gram negative bacteria differ in their sensitivity to cold plasma

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Mai-Prochnow, Anne; Clauson, Maryse; Hong, Jungmi; Murphy, Anthony B.

2016-12-01

Cold atmospheric-pressure plasma (CAP) is a relatively new method being investigated for antimicrobial activity. However, the exact mode of action is still being explored. Here we report that CAP efficacy is directly correlated to bacterial cell wall thickness in several species. Biofilms of Gram positive Bacillus subtilis, possessing a 55.4 nm cell wall, showed the highest resistance to CAP, with less than one log10 reduction after 10 min treatment. In contrast, biofilms of Gram negative Pseudomonas aeruginosa, possessing only a 2.4 nm cell wall, were almost completely eradicated using the same treatment conditions. Planktonic cultures of Gram negative Pseudomonas libanensis also had a higher log10 reduction than Gram positive Staphylococcus epidermidis. Mixed species biofilms of P. aeruginosa and S. epidermidis showed a similar trend of Gram positive bacteria being more resistant to CAP treatment. However, when grown in co-culture, Gram negative P. aeruginosa was more resistant to CAP overall than as a mono-species biofilm. Emission spectra indicated OH and O, capable of structural cell wall bond breakage, were present in the plasma. This study indicates that cell wall thickness correlates with CAP inactivation times of bacteria, but cell membranes and biofilm matrix are also likely to play a role.

Veillonella, Firmicutes: Microbes disguised as Gram negatives.

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Vesth, Tammi; Ozen, Aslı; Andersen, Sandra C; Kaas, Rolf Sommer; Lukjancenko, Oksana; Bohlin, Jon; Nookaew, Intawat; Wassenaar, Trudy M; Ussery, David W

2013-12-20

The Firmicutes represent a major component of the intestinal microflora. The intestinal Firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. Although most Firmicutes are Gram positive, members of the class Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared to 20 other Firmicutes genomes; a further 101 prokaryotic genomes were included, covering 26 phyla. Thus a total of 145 prokaryotic genomes were analyzed by various methods to investigate the apparent conflict of the Veillonella Gram stain and their taxonomic position within the Firmicutes. Comparison of the genome sequences confirms that the Negativicutes are distantly related to Clostridium spp., based on 16S rRNA, complete genomic DNA sequences, and a consensus tree based on conserved proteins. The genus Veillonella is relatively homogeneous: inter-genus pair-wise comparison identifies at least 1,350 shared proteins, although less than half of these are found in any given Clostridium genome. Only 27 proteins are found conserved in all analyzed prokaryote genomes. Veillonella has distinct metabolic properties, and significant similarities to genomes of Proteobacteria are not detected, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the

Revisiting the Gram-negative lipoprotein paradigm.

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LoVullo, Eric D; Wright, Lori F; Isabella, Vincent; Huntley, Jason F; Pavelka, Martin S

2015-05-01

The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

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Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.

2015-01-01

ABSTRACT   Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance  Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. PMID:25564466

Daptomycin treatment in Gram-positive vascular graft infections

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Francisco Arnaiz de las Revillas

2018-03-01

Full Text Available Background: Daptomycin is a bactericidal antibiotic approved for the treatment of skin and soft tissue infections and right-side endocarditis. However, there is a lack of published data outlining its usefulness in vascular graft infections (VGI. The aim of this study was to describe the clinical experience of daptomycin use in the treatment of VGI caused by Gram-positive bacteria. Methods: This was a retrospective cohort study of patients diagnosed with VGI receiving daptomycin at a tertiary care hospital during the period January 2010 to December 2012. Results: Of a total 1066 consecutive patients who had undergone vascular grafts (VG, 25 were diagnosed with VGI. Fifteen of these patients (11 prosthetic VG, three autologous VG, one both types received daptomycin (median dose 6.7 mg/kg/day, range 4.1–7.1 mg/kg/day; median age 69 years, range 45–83 years; 80% male. The infected bypass was removed in 13 cases. The most common reason for selecting daptomycin was kidney failure (53%. The Gram-positive organisms isolated were coagulase-negative Staphylococcus (n = 10, Staphylococcus aureus (n = 3 (two methicillin-resistant S. aureus, Enterococcus faecium (n = 2, and Enterococcus faecalis (n = 1. The mean follow-up was 69 months (interquartile range 48–72 months. Ten patients (66.7% achieved complete healing of the VGI. A recurrence of the infection was observed in 100% of patients in whom the bypass was not removed. Among patients who did not achieve complete healing, one needed a supracondylar amputation and one died as a consequence of infection. Five patients received treatment with rifampicin in addition to daptomycin and they were all cured. Conclusions: The use of daptomycin and surgery for Gram-positive VGI was effective and well tolerated, and this may be a good alternative for the treatment of VGI in patients with peripheral arterial disease in whom renal insufficiency is common. Keywords: Daptomycin, Gram-positive, Vascular

Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

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Lu, Hoang D.; Yang, Shirley S.; Wilson, Brian K.; McManus, Simon A.; Chen, Christopher V. H.-H.; Prud'homme, Robert K.

2017-04-01

Antimicrobial resistance is a healthcare problem of increasing significance, and there is increasing interest in developing new tools to address bacterial infections. Bacteria-targeting nanoparticles hold promise to improve drug efficacy, compliance, and safety. In addition, nanoparticles can also be used for novel applications, such as bacterial imaging or bioseperations. We here present the use of a scalable block-copolymer-directed self-assembly process, Flash NanoPrecipitation, to form zinc(II)-bis(dipicolylamine) modified nanoparticles that bind to both Gram-positive and Gram-negative bacteria with specificity. Particles have tunable surface ligand densities that change particle avidity and binding efficacy. A variety of materials can be encapsulated into the core of the particles, such as optical dyes or iron oxide colloids, to produce imageable and magnetically active bacterial targeting constructs. As a proof-of-concept, these particles are used to bind and separate bacteria from solution in a magnetic column. Magnetic manipulation and separation would translate to a platform for pathogen identification or removal. These magnetic and targeted nanoparticles enable new methods to address bacterial infections.

Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

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Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

2015-01-01

Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

Mid-infrared spectroscopic assessment of nanotoxicity in gram-negative vs. gram-positive bacteria.

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Heys, Kelly A; Riding, Matthew J; Strong, Rebecca J; Shore, Richard F; Pereira, M Glória; Jones, Kevin C; Semple, Kirk T; Martin, Francis L

2014-03-07

Nanoparticles appear to induce toxic effects through a variety of mechanisms including generation of reactive oxygen species (ROS), physical contact with the cell membrane and indirect catalysis due to remnants from manufacture. The development and subsequent increasing usage of nanomaterials has highlighted a growing need to characterize and assess the toxicity of nanoparticles, particularly those that may have detrimental health effects such as carbon-based nanomaterials (CBNs). Due to interactions of nanoparticles with some reagents, many traditional toxicity tests are unsuitable for use with CBNs. Infrared (IR) spectroscopy is a non-destructive, high throughput technique, which is unhindered by such problems. We explored the application of IR spectroscopy to investigate the effects of CBNs on Gram-negative (Pseudomonas fluorescens) and Gram-positive (Mycobacterium vanbaalenii PYR-1) bacteria. Two types of IR spectroscopy were compared: attenuated total reflection Fourier-transform infrared (ATR-FTIR) and synchrotron radiation-based FTIR (SR-FTIR) spectroscopy. This showed that Gram-positive and Gram-negative bacteria exhibit differing alterations when exposed to CBNs. Gram-positive bacteria appear more resistant to these agents and this may be due to the protection afforded by their more sturdy cell wall. Markers of exposure also vary according to Gram status; Amide II was consistently altered in Gram-negative bacteria and carbohydrate altered in Gram-positive bacteria. ATR-FTIR and SR-FTIR spectroscopy could both be applied to extract biochemical alterations induced by each CBN that were consistent across the two bacterial species; these may represent potential biomarkers of nanoparticle-induced alterations. Vibrational spectroscopy approaches may provide a novel means of fingerprinting the effects of CBNs in target cells.

Bloodstream Infections in a Neonatal Intensive Care Unit

OpenAIRE

Mehmet Sah Ipek

2016-01-01

Aim: To determine the pattern of bloodstream infections (BSIs) and antimicrobial susceptibility of pathogens in a neonatal intensive care unit (NICU).Material and Method: Positive hemoculture of neonates diagnosed with nosocomial sepsis from March 2011 to March 2014 in the NICU of Diyarbakir Maternity and Children%u2019s Hospital, in the southeastern region of Anatolia, Turkey, were retrospectively reviewed. Results: A total of 148 pathogens were isolated in 142 neonates. The most common micr...

Infectious tenosynovitis with bloodstream infection caused by Erysipelothrix rhusiopathiae, a case report on an occupational pathogen.

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Hofseth, Kristine; Dalen, Håvard; Kibsgaard, Leif; Nebb, Solrun; Kümmel, Angela; Mehl, Arne

2017-01-05

Erysipelothrix rhusiopathiae is an established animal pathogen, which may cause infections in humans. It is a gram-positive rod and found in the tonsils or the digestive tracts of animals. The bacterium is occupationally related, as usually only people with frequent animal contacts are infected. We report a case of a patient who was admitted with an infectious tenosynovitis with bloodstream infection due to E. rhusiopathiae, and to our knowledge, this is the first report of a tenosynovitis with systemic manifestation associated with this bacterium. A 52-year old Norwegian man, who worked with transportation of swine cadavers, was admitted to the local hospital with sepsis and unknown focus of infection. A few days earlier he had an injury to the skin of one of his fingers that later proved to be infected with E. rhusiopathiae. There were no other causes for his symptoms than the infectious tenosynovitis with systemic manifestation. The infection resolved on treatment with antibiotics and surgery. A transoesophageal echocardiogram was performed to exclude endocarditis, which may be associated with this pathogen. This case report highlights the importance of clinicians being aware of this bacterium, and we describe risk factors for infection, differences in the clinical manifestations of the disease, challenges with diagnosing the bacterium and adverse effects of immunosuppressive drugs. Recommended treatment is appropriate antibiotic therapy and adequate debridement and surgical drainage of the tendon sheath.

Detection and Antibiotic Susceptibility Pattern of Biofilm Producing Gram Positive and Gram Negative Bacteria Isolated From a Tertiary Care Hospital of Pakistan

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Iqbal, M.

2011-01-01

Full Text Available Microorganisms adhere to non-living material or living tissue, and form biofilms made up of extracellular polymers/slime. Biofilm-associated microorganisms behave differently from free-floating bacteria with respect to growth rates and ability to resist antimicrobial treatments and therefore pose a public health problem. The objective of this study is to detect the prevalence of biofilm producers among Gram positive and Gram negative bacteria isolated from clinical specimens, and to study their antimicrobial susceptibility pattern. The study was carried out from October 2009 to March 2010, at the Department of Microbiology, Army Medical College/ National University of Sciences and Technology (NUST, Rawalpindi, Pakistan. Clinical specimens were received from various wards of a tertiary care hospital. These were dealt by standard microbiological procedures. Gram positive and Gram negative bacteria isolated were subjected to biofilm detection by congo red agar method (CRA. Antimicrobial susceptibility testing of those isolates, which showed positive results (slime production, was done according to the Kirby-Bauer disc diffusion technique. A total of 150 isolates were tested for the production of biofilm/slime. Among them, 81 isolates showed positive results. From these 81, 51 were Gram positive and 30 were Gram negative. All the 81(54% slime producers showed reduced susceptibility to majority of antibiotics. Bacterial biofilms are an important virulence factor associated with chronic nosocomial infection. Detection of biofilm forming organisms can help in appropriate antibiotic choice.

Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

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Evelyn D Olthof

Full Text Available Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions.Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

[Left-sided endocarditis due to gram-negative bacilli: epidemiology and clinical characteristics].

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Noureddine, Mariam; de la Torre, Javier; Ivanova, Radka; Martínez, Francisco José; Lomas, Jose María; Plata, Antonio; Gálvez, Juan; Reguera, Jose María; Ruiz, Josefa; Hidalgo, Carmen; Luque, Rafael; García-López, María Victoria; de Alarcón, Arístides

2011-04-01

The aim of this study is to describe the epidemiological, clinical characteristics, and outcome of patients with left-side endocarditis caused by gram-negative bacteria. Prospective multicenter study of left-sided infective endocarditis reported in the Andalusian Cohort for the Study of Cardiovascular Infections between 1984 and 2008. Among the 961 endocarditis, 24 (2.5%) were caused by gram-negative bacilli. The most common pathogens were Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica. Native valves (85.7%) were mainly affected, most of them with previous valve damage (57%). Comorbidity was greater (90% vs 39%; P=.05) than in endocarditis due to other microorganism, the most frequent being, diabetes, hepatic cirrhosis and neoplasm. A previous manipulation was found in 47.6% of the cases, and 37% were considered hospital-acquired. Renal failure (41%), central nervous system involvement (33%) and ventricular dysfunction (45%) were the most frequent complications. Five cases (21%) required cardiac surgery, mostly due to ventricular dysfunction. More than 50% of cases were treated with aminoglycosides, but this did not lead to a better outcome or prognosis. Mortality (10 patients) was higher than that reported with other microorganisms (41% vs 35%; P=.05). Left-sided endocarditis due to gram-negative bacilli is a rare disease, which affects patients with major morbidities and often with a previous history of hospital manipulations. Cardiac, neurological and renal complications are frequent and associated with a high mortality. The association of aminoglycosides in the antimicrobial treatment did not involve a better outcome or prognosis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients.

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Karaaslan, Ayşe; Çağan, Eren; Kadayifci, Eda Kepenekli; Atıcı, Serkan; Akkoç, Gülşen; Yakut, Nurhayat; Demir, Sevliya Öcal; Soysal, Ahmet; Bakır, Mustafa

2016-11-01

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

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

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Ayşe Karaaslan

2016-12-01

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

Risk factors for central line-associated bloodstream infection in pediatric oncology patients with a totally implantable venous access port: A cohort study.

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Viana Taveira, Michelle Ribeiro; Lima, Luciana Santana; de Araújo, Cláudia Corrêa; de Mello, Maria Júlia Gonçalves

2017-02-01

Totally implantable venous access ports (TIVAPs) are used for prolonged central venous access, allowing the infusion of chemotherapy and other fluids and improving the quality of life of children with cancer. TIVAPs were developed to reduce the infection rates associated with central venous catheters; however, infectious events remain common and have not been fully investigated in pediatric oncology patients. A retrospective cohort was formed to investigate risk factors for central line-associated bloodstream infection (CLABSI) in pediatric cancer patients. Sociodemographic, clinical, and TIVAP insertion-related variables were evaluated, with the endpoint being the first CLABSI. A Kaplan-Meier analysis was performed to determine CLABSI-free catheter survival. Overall, 188 children were evaluated over 77,541 catheter days, with 94 being diagnosed with CLABSI (50%). Although coagulase-negative staphylococci were the pathogens most commonly isolated, Gram-negative microorganisms (46.8%) were also prevalent. In the multivariate analysis, factors that increased the risk for CLABSI were TIVAP insertion prior to chemotherapy (risk ratio [RR] = 1.56; P Risk factors for CLABSI in pediatric cancer patients with a TIVAP may be related to the severity of the child's condition at catheter insertion. Insertion of the catheter before chemotherapy and unfavorable conditions such as malnutrition and bone marrow aplasia can increase the risk of CLABSI. Protocols must be revised and surveillance increased over the first 10 weeks of treatment. © 2016 Wiley Periodicals, Inc.

Lack of clinical utility of urine gram stain for suspected urinary tract infection in pediatric patients.

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Cantey, Joseph B; Gaviria-Agudelo, Claudia; McElvania TeKippe, Erin; Doern, Christopher D

2015-04-01

Urinary tract infection (UTI) is one of the most common infections in children. Urine culture remains the gold standard for diagnosis, but the utility of urine Gram stain relative to urinalysis (UA) is unclear. We reviewed 312 pediatric patients with suspected UTI who had urine culture, UA, and urine Gram stain performed from a single urine specimen. UA was considered positive if ≥10 leukocytes per oil immersion field were seen or if either nitrates or leukocyte esterase testing was positive. Urine Gram stain was considered positive if any organisms were seen. Sensitivity, specificity, and positive and negative predictive values were calculated using urine culture as the gold standard. Thirty-seven (12%) patients had a culture-proven UTI. Compared to urine Gram stain, UA had equal sensitivity (97.3% versus 97.5%) and higher specificity (85% versus 74%). Empirical therapy was prescribed before the Gram stain result was known in 40 (49%) patients and after in 42 (51%) patients. The antibiotics chosen did not differ between the two groups (P=0.81), nor did they differ for patients with Gram-negative rods on urine Gram stain compared to those with Gram-positive cocci (P=0.67). From these data, we conclude that UA has excellent negative predictive value that is not enhanced by urine Gram stain and that antibiotic selection did not vary based on the urine Gram stain result. In conclusion, the clinical utility of urine Gram stain does not warrant the time or cost it requires. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dose-Dependent Antimicrobial Activity of Silver Nanoparticles on Polycaprolactone Fibers against Gram-Positive and Gram-Negative Bacteria

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Erick Pazos-Ortiz

2017-01-01

Full Text Available The adhesion ability and adaptability of bacteria, coupled with constant use of the same bactericides, have made the increase in the diversity of treatments against infections necessary. Nanotechnology has played an important role in the search for new ways to prevent and treat infections, including the use of metallic nanoparticles with antibacterial properties. In this study, we worked on the design of a composite of silver nanoparticles (AgNPS embedded in poly-epsilon-caprolactone nanofibers and evaluated its antimicrobial properties against various Gram-positive and Gram-negative microorganisms associated with drug-resistant infections. Polycaprolactone-silver composites (PCL-AgNPs were prepared in two steps. The first step consisted in the reduction in situ of Ag+ ions using N,N-dimethylformamide (DMF in tetrahydrofuran (THF solution, and the second step involved the simple addition of polycaprolactone before electrospinning process. Antibacterial activity of PCL-AgNPs nanofibers against E. coli, S. mutans, K. pneumoniae, S. aureus, P. aeruginosa, and B. subtilis was evaluated. Results showed sensibility of E. coli, K. pneumoniae, S. aureus, and P. aeruginosa, but not for B. subtilis and S. mutans. This antimicrobial activity of PCL-AgNPs showed significant positive correlations associated with the dose-dependent effect. The antibacterial property of the PCL/Ag nanofibers might have high potential medical applications in drug-resistant infections.

Pulmonary infiltrates during community acquired Gram-negative bacteremia

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Fjeldsøe-Nielsen, Hans; Gjeraa, Kirsten; Berthelsen, Birgitte G

2013-01-01

The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark.......The primary aim of this study was to describe the frequency of pulmonary infiltrates on chest X-ray (CXR) during community acquired Gram-negative bacteremia at a single centre in Denmark....

Comparative activity of ceftobiprole against Gram-positive and Gram-negative isolates from Europe and the Middle East: the CLASS study.

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Rossolini, Gian M; Dryden, Matthew S; Kozlov, Roman S; Quintana, Alvaro; Flamm, Robert K; Läuffer, Jörg M; Lee, Emma; Morrissey, Ian; CLASS Study Group

2011-01-01

to assess the in vitro activity of ceftobiprole and comparators against a recent collection of Gram-positive and Gram-negative pathogens, in order to detect potential changes in susceptibility patterns, and to evaluate the Etest assay for ceftobiprole susceptibility testing. contemporary Gram-positive and Gram-negative isolates (excluding extended-spectrum β-lactamase-producing isolates) from across Europe and the Middle East were collected, and their susceptibility to ceftobiprole, vancomycin, teicoplanin, linezolid, ceftazidime and cefepime was assessed using the Etest method. Quality testing [using Etest and broth microdilution (BMD)] was conducted at a central reference laboratory. some 5041 Gram-positive and 4026 Gram-negative isolates were included. Against Gram-positive isolates overall, ceftobiprole had the lowest MIC50 (0.5 mg/L), compared with 1 mg/L for its comparators (vancomycin, teicoplanin and linezolid). Against methicillin-resistant Staphylococcus aureus, all four agents had a similar MIC90 (2 mg/L), but ceftobiprole had a 4-fold better MIC90 (0.5 mg/L) against methicillin-susceptible strains. Only 38 Gram-positive isolates were confirmed as ceftobiprole resistant. Among Gram-negative strains, 86.9%, 91.7% and 95.2% were susceptible to ceftobiprole, ceftazidime and cefepime, respectively. Pseudomonas aeruginosa was less susceptible to all three antimicrobials than any other Gram-negative pathogen. There was generally good agreement between local Etest results and those obtained at the reference laboratory (for ceftobiprole: 86.8% with Gram-negatives; and 94.7% with Gram-positives), as well as between results obtained by BMD and Etest methods (for ceftobiprole: 98.2% with Gram-negatives; and 98.4% with Gram-positives). ceftobiprole exhibits in vitro activity against a wide range of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains. No changes in its known susceptibility profile were identified.

A coagulase-negative and non-haemolytic strain of Staphylococcus aureus for investigating the roles of SrtA in a murine model of bloodstream infection.

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Wang, Lin; Bi, Chongwei; Wang, Tiedong; Xiang, Hua; Chen, Fuguang; Hu, Jinping; Liu, Bingrun; Cai, Hongjun; Zhong, Xiaobo; Deng, Xuming; Wang, Dacheng

2015-08-01

Sortase A (SrtA) is a cysteine transpeptidase and virulence factor from Staphylococcus aureus (S. aureus) that catalyses the attachment and display of surface proteins on the cell wall, thereby mediating bacterial adhesion to host tissues, host-cell entry and evasion of the immune response. As a result, SrtA has become an important target in the development of therapies for S. aureus infections. In this study, we used the new reference strain S. aureus Newman D2C to investigate the role of SrtA in a murine model of bloodstream infection, when the impact of coagulase and haemolysin is excluded. The results suggested that deletion of SrtA reduced the bacterial burden on the heart, liver and kidneys by blunting the host proinflammatory cytokine response at an early point in infection. Kidneys, but not heart or liver, formed abscesses on the sixth day following non-lethal infection, and this effect was diminished by SrtA mutation. These findings indicate that SrtA is a determining virulence factor in lethality and formation of renal abscesses in mice followed by S. aureus bloodstream infection. We have thus established a convenient in vitro and mouse model for developing SrtA-targeted therapeutic strategies. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prediction of lipoprotein signal peptides in Gram-negative bacteria.

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Juncker, Agnieszka S; Willenbrock, Hanni; Von Heijne, Gunnar; Brunak, Søren; Nielsen, Henrik; Krogh, Anders

2003-08-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions by the HMM agree well with the experimentally verified lipoproteins. A neural network-based predictor was developed for comparison, and it gave very similar results. LipoP is available as a Web server at www.cbs.dtu.dk/services/LipoP/.

Incidence of carbapenem resistant nonfermenting gram negative bacilli from patients with respiratory infections in the intensive care units

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Gladstone P

2005-01-01

Full Text Available Resistance to carbapenems is commonly seen in nonfermenting gram negative bacilli (NFGNB. We document herein the prevalence of carbapenem resistance in NFGNB isolated from patients with respiratory tract infections in the intensive care units (ICUs. A total of 460 NFGNB were isolated from 606 endotracheal aspirate specimens during January through December 2003, of which 56 (12.2% were found to be resistant to imipenem and meropenem. Of these, 24 (42.8% were Pseudomonas aeruginosa , 8 (14.2% were Acinetobacter spp. and 24 (42.8% were other NFGNB. Stringent protocols such as antibiotic policies and resistance surveillance programs are mandatory to curb these bacteria in ICU settings.

In vitro activity of XF-73, a novel antibacterial agent, against antibiotic-sensitive and -resistant Gram-positive and Gram-negative bacterial species.

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Farrell, David J; Robbins, Marion; Rhys-Williams, William; Love, William G

2010-06-01

The antibacterial activity of XF-73, a dicationic porphyrin drug, was investigated against a range of Gram-positive and Gram-negative bacteria with known antibiotic resistance profiles, including resistance to cell wall synthesis, protein synthesis, and DNA and RNA synthesis inhibitors as well as cell membrane-active antibiotics. Antibiotic-sensitive strains for each of the bacterial species tested were also included for comparison purposes. XF-73 was active [minimum inhibitory concentration (MIC) 0.25-4 mg/L] against all of the Gram-positive bacteria tested, irrespective of the antibiotic resistance profile of the isolates, suggesting that the mechanism of action of XF-73 is unique compared with the major antibiotic classes. Gram-negative activity was lower (MIC 1 mg/L to > 64 mg/L). Minimum bactericidal concentration data confirmed that the activity of XF-73 was bactericidal. Time-kill kinetics against healthcare-associated and community-associated meticillin-resistant Staphylococcus aureus isolates demonstrated that XF-73 was rapidly bactericidal, with > 5 log(10) kill obtained after 15 min at 2 x MIC, the earliest time point sampled. The post-antibiotic effect (PAE) for XF-73 under conditions where the PAE for vancomycin was 5.4 h. XF-73 represents a novel broad-spectrum Gram-positive antibacterial drug with potentially beneficial characteristics for the treatment and prevention of Gram-positive bacterial infections. 2010. Published by Elsevier B.V.

Central Venous Catheters and Bloodstream Infection During Induction Therapy in Children With Acute Lymphoblastic Leukemia

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Bergmann, Kristin; Hasle, Henrik; Asdahl, Peter

2016-01-01

The purpose of the study was to assess the risk of firsttime bloodstream infection (BSI) according to type of central venous catheter (CVC) during induction therapy in children with acute lymphoblastic leukemia (ALL). Patients eligible for our analysis were all newly diagnosed children with ALL......-negative blood isolates occurred more frequently in patients with a TE, and that lower incidences of BSI were detected in patients older than 9 years with a TE, and in patients with T-ALL. It is concluded that the type of CVC inserted at diagnosis has no impact upon the risk of BSI in patients with ALL...

Spread of resistant gram negatives in a Sri Lankan intensive care unit.

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Tissera, Kavinda; Liyanapathirana, Veranja; Dissanayake, Nilanthi; Pinto, Vasanthi; Ekanayake, Asela; Tennakoon, Manjula; Adasooriya, Dinuka; Nanayakkara, Dulmini

2017-07-11

Infections with multi drug resistant (MDR) organisms are a major problem in intensive care units (ICUs). Proper infection control procedures are mandatory to combat the spread of resistant organisms within ICUs. Well stablished surveillance programmes will enhance the adherence of the staff to infection control protocols. The study was conducted to assess the feasibility of using basic molecular typing methods and routine hospital data for laboratory surveillance of resistance organisms in resource limited settings. A retrospective study was conducted using consecutive Gram negative isolates obtained from an ICU over a six month period. Antibiotic sensitivity patterns and random amplified polymorphic DNA (RAPD) based typing was performed on the given isolates. Of the seventy isolates included in the study, seven were E.coli. All E.coli were MDRs and Extended Spectrum β lactamse (ESBL) producers carrying bla CTX-M . Fourteen isolates were K.pneumoniae, and all were MDRs and ESBL producers. All K.pneumoniae harboured bla SHV while 13 harboured bla CTX-M . The MDR rate among P.aeruginosa was 13% (n=15) while all acinetobacters (n=30) were MDRs. Predominant clusters were identified within all four types of Gram negatives using RAPD and the ICU stay of patients overlapped temporally. We propose that simple surveillance methods like RAPD based typing and basic hospital data can be used to convince hospital staff to adhere to infection control protocols more effectively, in low and middle income countries.

Pink-pigmented non-fermentative gram-negative rods associated with human infections: a clinical and diagnostic challenge.

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Hogue, R; Graves, M; Moler, S; Janda, J M

2007-06-01

Over the past several decades, the appearance of pink-pigmented bacteria in clinical specimens has gone from being a microbiologic curiosity in the clinical laboratory to the recognition of these aerobic microorganisms as etiologic agents of human disease, most notably bloodstream infections. Advances in the fields of molecular taxonomy and phylogenetics indicate that at least four distinct genera and eight different species are associated with clinical infections in susceptible patient populations. However, these bacteria are slow growing and present multiple diagnostic challenges to the microbiology laboratory including culture, isolation, and identification to species rank. This article provides a current review of these unusual non-fermentative chromogenic bacteria including their disease spectrum, taxonomy, and laboratory identification. The review also highlights the pitfalls or shortcomings we currently have in our knowledge of these microbes and their disease-producing capabilities.

Protamine-induced permeabilization of cell envelopes of gram-positive and gram-negative bacteria

DEFF Research Database (Denmark)

Johansen, Charlotte; Verheul, A.; Gram, Lone

1997-01-01

carboxyfluorescein and ATP after 2 to 5 min. Maximum antibacterial activity was reached at alkaline pH and in the absence of divalent cations. The efficient permeabilization of cell envelopes of both gram-positive and gram-negative bacteria suggests that protamine causes a general disruption of the cell envelope...

Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report

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Balaji Veeraraghavan

2018-01-01

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

Probing interaction of Gram-positive and Gram-negative bacterial cells with ZnO nanorods

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Jain, Aanchal; Bhargava, Richa; Poddar, Pankaj, E-mail: p.poddar@ncl.res.in

2013-04-01

In the present work, the physiological effects of the ZnO nanorods on the Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Aerobacter aerogenes) bacterial cells have been studied. The analysis of bacterial growth curves for various concentrations of ZnO nanorods indicates that Gram positive and Gram negative bacterial cells show inhibition at concentrations of ∼ 64 and ∼ 256 μg/mL respectively. The marked difference in susceptibility towards nanorods was also validated by spread plate and disk diffusion methods. In addition, the scanning electron micrographs show a clear damage to the cells via changed morphology of the cells from rod to coccoid etc. The confocal optical microscopy images of these cells also demonstrate the reduction in live cell count in the presence of ZnO nanorods. These, results clearly indicate that the antibacterial activity of ZnO nanorods is higher towards Gram positive bacterium than Gram negative bacterium which indicates that the structure of the cell wall might play a major role in the interaction with nanostructured materials and shows high sensitivity to the particle concentration. Highlights: ► Effect of ZnO nanorods on the growth cycles of four bacterial strains. ► A relation has been established between growth rate of bacteria and concentration. ► Serious damage in the morphology of bacterial cells in the presence of ZnO nanorods. ► Microscopic studies to see the time dependent effect on bacterial cells.

Prospects and challenges of developing new agents for tough Gram-negatives.

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Meyer, Annette L

2005-10-01

Historically, the medical profession has been successful in treating most bacterial infections in humans with synthetic second- and third-generation antibiotics. Recently, the prospects for continued success have dimmed with the increase in multidrug-resistant stains of bacteria. Infections caused by the Gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter spp. in particular have increased in frequency and severity, and become progressively more difficult to treat. Contributors to disease severity include chronic infections due to mutator strains, persister cells and biofilms. The worst-case scenario of infections susceptible only to toxic polymixins is now a reality. The need to address the treatment of multidrug-resistant pathogens with innovative combination approaches and/or novel antibacterial agents is occurring in the context of reduced investment in antimicrobial drug discovery by the pharmaceutical industry.

Catheter Removal versus Retention in the Management of Catheter-Associated Enterococcal Bloodstream Infections

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Jonas Marschall

2013-01-01

Full Text Available BACKGROUND: Enterococci are an important cause of central venous catheter (CVC-associated bloodstream infections (CA-BSI. It is unclear whether CVC removal is necessary to successfully manage enterococcal CA-BSI.

Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria.

Science.gov (United States)

El Salabi, Allaaeddin; Walsh, Timothey R; Chouchani, Chedly

2013-05-01

Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.

Emergence of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Denmark

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Larsen, Jesper; Petersen, Andreas; Larsen, Anders R.

2017-01-01

Background: Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream...

Antimicrobial Activity of Carbon Nanoparticles Isolated from Natural Sources against Pathogenic Gram-Negative and Gram-Positive Bacteria

International Nuclear Information System (INIS)

Varghese, S.; Jose, S.; Varghese, S.; Kuriakose, S.; Jose, S.

2013-01-01

This paper describes the isolation of carbon nanoparticles (CNPs) from kitchen soot, characterization of the CNPs by UV/visible spectroscopy, SEM and XRD, and their antimicrobial action. The antibacterial activity of the isolated carbon nanoparticles was tested against various pathogenic bacterial strains such as Gram-negative Proteus refrigere and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus and Streptococcus haemolyticus. The inhibition zones were measured, and it was found that the carbon nanoparticles isolated from natural sources are active against these Gram-negative and Gram-positive bacterial strains

Gram-Negative Bacterial Wound Infections

Science.gov (United States)

2014-05-01

Bovine Tuberculosis in Cattle Farms in Zaria and Kaduna and Possible Transmission Through Milk P. N. Mbianga, V. J. Umoh, A. I. 0, K. C. A; Ahmadu...Pathogenic Escherichia coli R. M. Ramirez, M-X. Haro, P. Miranda, S-H. Sanchez, L-E. Vidales; Univ. Aut6noma de Zacatecas, Zacatecas, Mexico 517...isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain

suPAR remains uninfluenced by surgery in septic patients with bloodstream infection

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Rabensteiner, Jasmin

2016-07-01

Full Text Available Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively ( 0.642; 0.773; 0.087. In contrast, a slight decrease of IL-6 ( 0.599 was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP ( 0.028 and PCT and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (<0.001, while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP ( 0.005 and PCT ( 0.005 was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.

Tsukamurella catheter-related bloodstream infection in a pediatric patient with pulmonary hypertension

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Kristen A. Wendorf

2010-03-01

Full Text Available Catheter-related bloodstream infections (CR-BSI are important complications in patients with long-term indwelling central venous catheters. In this report, we present the case of a 14-year-old male with pulmonary hypertension treated with continuous treprostinil infusion, who presented with a CR-BSI caused by a Tsukamurella species. This case highlights the potential for this unusual organism to cause infection in immunocompetent patients.

Resistant gram-negative bacilli and antibiotic consumption in zarqa, jordan

International Nuclear Information System (INIS)

Bataineh, H.A.; Alrashed, K.M.

2007-01-01

To investigate the prevalence of antibiotic resistance among gram-negative bacteria in relation to antibiotic use in Prince Hashem Hospital (PHH), Jordan. One hundred consecutive gram-negative bacterial isolates from different sites were collected from patients admitted to the ICU at PHH. The susceptibilities of the strains to 12 antibiotics were performed and interpreted. The quantities and the numbers of the patients discharged on antibiotics and the quantities consumed were obtained from the hospital pharmacy records. The most common isolate was P. aeruginosa (n=21) The most common site of isolation was the respiratory tract (65%), The highest susceptibility was to piperacillin/ tazobactam(78%), and the lowest was to cefuroxime(34%). The aminoglycosides gentamicin and amikacin were active against 71% and 73% of the isolates respectively, Ciprofloxacin was active against 75% of the isolates. The most frequently used antibiotics were the third-generation cephalosporins ceftriaxone and ceftazidime, followed by imipenem and amikacin. Antibiotic resistance surveillance programs associated with registration of antibiotic consumption are necessary to promote optimal use of antibiotics. Rational prescribing of antibiotics should be encouraged through educational programs, surveillance and audit. Proper infection control measures should be practiced to prevent horizontal transfer of drug-resistant organisms. (author)

Prevalence and risk factors for CTX-M gram-negative bacteria in hospitalized patients at a tertiary care hospital in Kilimanjaro, Tanzania

DEFF Research Database (Denmark)

Sonda, Tolbert; Kumburu, Happiness; van Zwetselaar, Marco

2018-01-01

Emergence and spread of extended spectrum beta-lactamase (ESBL)-producing gram-negative bacteria, mainly due to CTX-M, is a major global public health problem. Patients infected with ESBL-producing gram-negative bacteria have an increased risk of treatment failure and death. We investigated...... 2015 were fully genome sequenced. The prevalence of ESBL-producing gram-negative bacteria was determined based on the presence of blaCTX-M. The odds ratio (OR) and risk factors for ESBL-producing gram-negative bacteria due to CTX-M were assessed using logistic regression models. The overall CTX......-M prevalence (95% CI) was 13.6% (10.1–18.1). Adjusted for other factors, the OR of CTX-M gram-negative bacteria for patients previously hospitalized was 0.26 (0.08–0.88), p = 0.031; the OR for patients currently on antibiotics was 4.02 (1.29–12.58), p = 0.017; the OR for patients currently on ceftriaxone was 0...

Patients with Central Lines - What You Need to Know to Avoid a Bloodstream Infection PSA (:60)

Centers for Disease Control (CDC) Podcasts

This 60 second PSA is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.

Probing the Penetration of Antimicrobial Polymyxin Lipopeptides into Gram-Negative Bacteria

Science.gov (United States)

2015-01-01

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative ‘superbugs’ has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains. PMID:24635310

Comparing the harmful effects of nontuberculous mycobacteria and Gram negative bacteria on lung function in patients with cystic fibrosis

DEFF Research Database (Denmark)

Qvist, Tavs; Taylor-Robinson, David; Waldmann, Elisabeth

2015-01-01

BACKGROUND: To better understand the relative effects of infection with nontuberculous mycobacteria and Gram negative bacteria on lung function decline in cystic fibrosis, we assessed the impact of each infection in a Danish setting. METHODS: Longitudinal registry study of 432 patients with cystic...

[Antimicrobial susceptibility patterns of Gram-negative bacteria isolated in urinary tract infections in Venezuela: Results of the SMART study 2009-2012].

Science.gov (United States)

Guevara, Napoleón; Guzmán, Manuel; Merentes, Altagracia; Rizzi, Adele; Papaptzikos, Juana; Rivero, Narlesky; Oranges, Carmela; Vlllarroel, Héctor; Limas, Yoxsivell

2015-12-01

Antimicrobial resistance of pathogens causing urinary tract infection (UTI) is a growing problem, which complicates their effective treatment. Surveillance is needed to guide appropriate empiric therapy. to describe the susceptibility patterns of Gram-negative bacteria isolated of patients with UTI to twelve antibiotics as part of the Study for Monitoring Antimicrobial Resistance Trends in Venezuela. Between 2009-2012 a total of 472 Gram-negative bacteria were isolated from hospitalized patients with UTI. The isolates were sent to Central Laboratory (Central Laboratory of International Health Management Associates) to confirm their identification, and to make susceptibility testing as recommended by the Clinical and Laboratory Standards Institute. Enterobacteriacea comprised 96.6% of the total, where Escherichia coli (76.9%) and Klebsiella pneumoniae (10.6%) were the most frequent. Extended-spectrum β-lactamases (ESBL) was detected in 21.6% of isolates. Top antimicrobial activity were ertapenem, imipenem, and amikacin (> 90.0%), slightly lower for amikacin (85.1%) in ESBL-producing strains. Resistance rates to fluoroquinolones and ampicillin/sulbactam were high (40 y 64%, respectively). These data suggest a necessary revision of the therapeutic regimens for the empirical treatment of UTI in Venezuela.

Automated Interpretation of Blood Culture Gram Stains by Use of a Deep Convolutional Neural Network.

Science.gov (United States)

Smith, Kenneth P; Kang, Anthony D; Kirby, James E

2018-03-01

Microscopic interpretation of stained smears is one of the most operator-dependent and time-intensive activities in the clinical microbiology laboratory. Here, we investigated application of an automated image acquisition and convolutional neural network (CNN)-based approach for automated Gram stain classification. Using an automated microscopy platform, uncoverslipped slides were scanned with a 40× dry objective, generating images of sufficient resolution for interpretation. We collected 25,488 images from positive blood culture Gram stains prepared during routine clinical workup. These images were used to generate 100,213 crops containing Gram-positive cocci in clusters, Gram-positive cocci in chains/pairs, Gram-negative rods, or background (no cells). These categories were targeted for proof-of-concept development as they are associated with the majority of bloodstream infections. Our CNN model achieved a classification accuracy of 94.9% on a test set of image crops. Receiver operating characteristic (ROC) curve analysis indicated a robust ability to differentiate between categories with an area under the curve of >0.98 for each. After training and validation, we applied the classification algorithm to new images collected from 189 whole slides without human intervention. Sensitivity and specificity were 98.4% and 75.0% for Gram-positive cocci in chains and pairs, 93.2% and 97.2% for Gram-positive cocci in clusters, and 96.3% and 98.1% for Gram-negative rods. Taken together, our data support a proof of concept for a fully automated classification methodology for blood-culture Gram stains. Importantly, the algorithm was highly adept at identifying image crops with organisms and could be used to present prescreened, classified crops to technologists to accelerate smear review. This concept could potentially be extended to all Gram stain interpretive activities in the clinical laboratory. Copyright © 2018 American Society for Microbiology.

Revisiting the gram-negative lipoprotein paradigm

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The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

A New Take on an Old Remedy: Generating Antibodies against Multidrug-Resistant Gram-Negative Bacteria in a Postantibiotic World.

Science.gov (United States)

Motley, Michael P; Fries, Bettina C

2017-01-01

With the problem of multidrug-resistant Gram-negative pathogens becoming increasingly dire, new strategies are needed to protect and treat infected patients. Though abandoned in the past, monoclonal antibody therapy against Gram-negative bacteria remains a potential solution and has potential advantages over the broad-spectrum antibiotics they were once replaced by. This Perspective reviews the prospect of utilizing monoclonal antibody therapy against these pathogens, as well as the challenges of doing so and the current therapy targets under investigation.

Metallo- β-lactamases among Multidrug Resistant (MDR Gram Negative Bacteria Isolated from Clinical Specimens during 2009 in Sanandaj, Kurdistan Province

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Himen Salimizand

2012-08-01

Full Text Available Background: Today, there are numerous reports about emerging multi drug resistant gram negative bacteria all around the world, especially in ICUs. Rarely, Metallo-β-lactamase (MBL enzymes are responsible for these cases. Study of MBLs for diagnosing and preventing distribution of the origin of infection are critical issues. In addition, we would like to compare the efficacy of Iranian and foreign- made antibiotic disks. Materials and Methods: During 2009 all entered clinical specimens to the laboratory tested for detecting gram negative bacteria. Isolated bacteria were tested by Kirby-Bauer method to antibiotic susceptibility test by Iranian and foreign (MAST disks. For gram negative carbapenem resistant isolates, PCR technique used to detect VIM, GIM, and SIM variants of MBLs.Results: During one year, 17890 clinical specimens referred Besat laboratory. The most specimen was Urine (8172 followed by blood culture (5190 that in which 1110 gram negative and positives isolated. Out of which, 778 (70% of isolates were gram negatives. MDR gram negatives were 157 (20.2%. Imipenem and meropenem were the most efficient antibiotics (all susceptible and ceftriaxone was the least (19 % susceptible. E. coli was the most prevalent isolate. 79 Gram negative isolates (10.1% were resistant to Iranian-made discs but all susceptible for foreign ones. All 79 isolates were tested by PCR for MBL genes, that, all were negative. Besides, Iranian imipenem and cefepime disks have had distinguishable difference in susceptibility of isolates.Conclusion: Fortunately, none of gram negative isolates were MBL producer, which revealed no colonization of MBL producing bacteria. Iranian-made disks appear efficient except for imipenem and cefepime.

Dustborne and airborne gram-positive and gram-negative bacteria in high versus low ERMI homes

Science.gov (United States)

The study aimed at investigating Gram-positive and Gram-negative bacteria in moldy and non-moldy homes, as defined by the home's Environmental Relative Moldiness Index (ERMI) value. The ERMI values were determined from floor dust samples in 2010 and 2011 and homes were classified...

Candida bloodstream infection: a clinical microbiology laboratory perspective.

Science.gov (United States)

Pongrácz, Júlia; Kristóf, Katalin

2014-09-01

The incidence of Candida bloodstream infection (BSI) has been on the rise in several countries worldwide. Species distribution is changing; an increase in the percentage of non-albicans species, mainly fluconazole non-susceptible C. glabrata was reported. Existing microbiology diagnostic methods lack sensitivity, and new methods need to be developed or further evaluation for routine application is necessary. Although reliable, standardized methods for antifungal susceptibility testing are available, the determination of clinical breakpoints remains challenging. Correct species identification is important and provides information on the intrinsic susceptibility profile of the isolate. Currently, acquired resistance in clinical Candida isolates is rare, but reports indicate that it could be an issue in the future. The role of the clinical microbiology laboratory is to isolate and correctly identify the infective agent and provide relevant and reliable susceptibility data as soon as possible to guide antifungal therapy.

Patients with Central Lines — What You Need to Know to Avoid a Bloodstream Infection

Centers for Disease Control (CDC) Podcasts

This podcast is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.

A Descriptive Study of Nosocomial Infections in an Adult Intensive Care Unit in Fiji: 2011-12

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Keshni Naidu

2014-01-01

Full Text Available Nosocomial infections in an intensive care unit (ICU are common and associated with a high mortality but there are no published data from the Oceania region. A retrospective study in Fiji’s largest ICU (2011-12 reported that 114 of a total 663 adult ICU admissions had bacteriological culture-confirmed nosocomial infection. The commonest sites of infection were respiratory and bloodstream. Gram negative bacteria were the commonest pathogens isolated, especially Klebsiella pneumoniae (extended-spectrum β-Lactamase-producing, Acinetobacter, and Pseudomonas species. Mortality for those with a known outcome was 33%. Improved surveillance and implementation of effective preventive interventions are needed.

How bacterial cell division might cheat turgor pressure - a unified mechanism of septal division in Gram-positive and Gram-negative bacteria.

Science.gov (United States)

Erickson, Harold P

2017-08-01

An important question for bacterial cell division is how the invaginating septum can overcome the turgor force generated by the high osmolarity of the cytoplasm. I suggest that it may not need to. Several studies in Gram-negative bacteria have shown that the periplasm is isoosmolar with the cytoplasm. Indirect evidence suggests that this is also true for Gram-positive bacteria. In this case the invagination of the septum takes place within the uniformly high osmotic pressure environment, and does not have to fight turgor pressure. A related question is how the V-shaped constriction of Gram-negative bacteria relates to the plate-like septum of Gram-positive bacteria. I collected evidence that Gram-negative bacteria have a latent capability of forming plate-like septa, and present a model in which septal division is the basic mechanism in both Gram-positive and Gram-negative bacteria. © 2017 WILEY Periodicals, Inc.

Blood culture procedures and diagnosis of Malassezia furfur bloodstream infections : Strength and weakness

NARCIS (Netherlands)

Iatta, Roberta; Battista, Michela; Miragliotta, Giuseppe; Boekhout, Teun; Otranto, Domenico; Cafarchia, Claudia

2017-01-01

The occurrence of Malassezia spp. bloodstream infections (BSIs) in neonatal intensive care unit was evaluated by using pediatric Isolator, BacT/Alert systems and central venous catheter (CVC) culture. The efficacy of BacT/Alert system in detecting Malassezia was assessed by conventional procedures,

Limitations in the use of Drosophila melanogaster as a model host for gram-positive bacterial infection

DEFF Research Database (Denmark)

Jensen, Rikke Lind; Pedersen, K.S.; Loeschcke, V

2007-01-01

resistance respectively, were subjected to infection by L. monocytogenes, S. aureus and E. coli. Mortality rates were comparable with that of the Oregon R strain. Conclusions: Use of the injection method shows the limitation of D. melanogaster as a model host for gram-positive bacteria as opportunistic......Aims: To examine sensitivities of various Drosophila melanogaster strains towards human pathogenic and nonpathogenic gram-positive bacteria. Methods and Results: The D. melanogaster Oregon R strain was infected by injecting the thorax with a needle containing Escherichia coli (negative control...... with the negative control. Infection with L. innocua, B. subtilis or C. maltaromaticum also resulted in a high fly mortality, whereas Lact. plantarum and P. acidilactici resulted in a slightly increased mortality. Four additional D. melanogaster lines, three of which had been selected for heat, cold and desiccation...

Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German Border Region-Impact of National Guidelines

NARCIS (Netherlands)

Köck, Robin; Siemer, Philipp; Esser, Jutta; Kampmeier, Stefanie; Berends, Matthijs S; Glasner, Corinna; Arends, Jan P; Becker, Karsten; Friedrich, Alexander W

2018-01-01

Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the

High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

Science.gov (United States)

Turner, Paul; Pol, Sreymom; Soeng, Sona; Sar, Poda; Neou, Leakhena; Chea, Phal; Day, Nicholas Pj; Cooper, Ben S; Turner, Claudia

2016-08-01

Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.

Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

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Jorge Calvo-Lon

2017-12-01

Full Text Available Purpose: Bloodstream infections (BSIs are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods: We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC. Descriptive statistics were used. Results: A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63% were males, and 128 cases of infection (78% were the result of gram-negative bacilli (GNB. Klebsiella pneumoniae (21%, Escherichia coli (21%, and Pseudomonas aeruginosa (15% were the most common microorganisms isolated. Gram-positive cocci (GPC were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10% and Staphyloccocus epidermidis (6%. With respect to tumor type, BSIs were more frequent in the GI tract (57% followed by head and neck (9% and genitourinary tract (8%. Regarding antibiotic susceptibility, only 17% (GNB expressed extended-spectrum beta-lactamase and 12% (GPC had methicillin resistance. Patients with CVCs (n = 59 were colonized mainly by GNB (78%. Overall the mortality rate at 30 days was about 30%. Conclusion: GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.

The clinical and microbiological characteristics of infections in burn patients from the Formosa Fun Coast Dust Explosion

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Tzu-Chao Lin

2018-04-01

Full Text Available Background/Purpose: Bloodstream infection is a leading cause of mortality among burn patients. This study aimed to evaluate the risk factors, causative pathogens, and the relationship between bloodstream infections and other infections among burn patients from the Formosa Fun Coast Dust Explosion. Methods: This retrospective study evaluated the demographic and clinical characteristics, infection types, causative pathogen(s, and isolates' antibiotic susceptibilities from patients who were hospitalized between June 27 and September 31, 2015. Results: Fifty-eight patients were admitted during the study period (36 males, mean age: 22.6 years. The mean burned total body surface area (TBSA was 40% for all patients. Eighteen (31% patients with mean TBSA of 80% had 66 episodes of bloodstream infections caused by 92 isolates. Twelve (18.2% episodes of bloodstream infections were polymicrobial. Acinetobacter baumannii (19, 20.7%, Ralstonia pickettii (17, 18.5%, and Chryseobacterium meningosepticum (13, 14.1% were the most common pathogens causing bloodstream infections. A high concordance rate of wound cultures with blood cultures was seen in Staphylococcus aureus (3, 75% and C. meningosepticum (8, 61.5% infections. However, no Ralstonia isolate was found in burn wounds of patients with Ralstonia bacteremia. A high concordance rate of central venous catheter cultures with blood cultures was noted in Ralstonia mannitolilytica (5, 62.5% and Chryseobacterium indologenes (3, 60% infections. Approximately 21.1% of A. baumannii strains were resistant to carbapenem. All S. aureus isolates were susceptible to methicillin. Conclusions: Waterborne bacteria should be considered in patients of burns with possible water contact. Empirical broad-spectrum antibiotics should be considered for patients who were hospitalized for severe sepsis, or septic shock with a large burn. Antibiotic treatment should be administered based on the specific pathogens and their detection

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes.

Science.gov (United States)

Costa, Patrícia de Oliveira; Atta, Elias Hallack; Silva, André Ricardo Araújo da

2015-01-01

This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Monomicrobial necrotizing fasciitis in a single center: the emergence of Gram-negative bacteria as a common pathogen

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D. Yahav

2014-11-01

Conclusions: In our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli. These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

Interventional strategies and current clinical experience with carbapenemase-producing Gram-negative bacteria.

Science.gov (United States)

Akova, M; Daikos, G L; Tzouvelekis, L; Carmeli, Y

2012-05-01

The wide dissemination of carbapenemase-producing Gram-negatives (CPGNs), including enterobacterial species and non-fermenters, has caused a public health crisis of global dimensions. These organisms cause serious infections in hospitalized patients, and are associated with increased mortality. Cross-transmission is common, and outbreaks may occur in healthcare facilities where the infection control practices are inadequate. CPGNs exhibit extensive drug-resistant phenotypes, complicate therapy, and limit treatment options. Systematic data on therapy are limited. However, regimens combining two or more active agents seem to be more efficacious than monotherapy in carbapenemase-producing Klebsiella pneumoniae infections. Strict infection control measures, including active surveillance for timely detection of colonized patients, separation of carriers from non-carriers, and contact precautions, are of utmost importance, and may be the only effective way of preventing the introduction and transmission of these bacteria in healthcare settings. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Selective bowel decontamination results in gram-positive translocation.

Science.gov (United States)

Jackson, R J; Smith, S D; Rowe, M I

1990-05-01

Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

Beta-lactam resistance in the gram negatives: increasing complexity of conditional, composite and multiply resistant phenotypes.

Science.gov (United States)

Iredell, Jon; Thomas, Lee; Espedido, Björn

2006-12-01

The greatest impact of microbiology data on clinical care is in the critically ill. Unfortunately, this is also the area in which microbiology laboratories are most often non-contributive. Attempts to move to rapid, culture-independent diagnostics are driven by the need to expedite urgent results. This is difficult in Gram-negative infection because of the complexity of the antibiotic resistance phenotype. Here, we discuss resistance to modern beta-lactams as a case in point. Recent outbreaks of transmissible carbapenem resistance among Gram-negative enteric pathogens in Sydney and Melbourne serve to illustrate the pitfalls of traditional phenotypical approaches. A better understanding of the epidemiology and mosaic nature of antibiotic resistance elements in the microflora is needed for us to move forward.

Antibacterial Activity of Silver-Graphene Quantum Dots Nanocomposites Against Gram-Positive and Gram-Negative Bacteria

Science.gov (United States)

Habiba, Khaled (Inventor); Makarov, Vladimir (Inventor); Weiner, Brad R (Inventor); Morell, Gerardo (Inventor)

2018-01-01

The invention provides a composite of silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) using pulsed laser synthesis. The nanocomposites were functionalized with polyethylene glycol (PEG). A concentration of 150 .mu.g/mL of Ag-GQDs, a non-toxic level for human cells, exhibits strong antibacterial activity against both Gram-Positive and Gram-Negative Bacteria.

The epidemiology, antibiograms and predictors of mortality among critically-ill patients with central line-associated bloodstream infections

Directory of Open Access Journals (Sweden)

Shin-Huei Kuo

2018-06-01

Conclusion: We identified Gram-negative bacteria as leading pathogens of CLABSIs in a Taiwan medical center, and good compliance to care bundle is associated with reduced CLABSI incidence rate. Malignancy, infection by MDROs or fungi, inadequate empirical or definite antimicrobial therapy are significant factors for 14-day mortality.

Diagnosing periprosthetic infection: false-positive intraoperative Gram stains.

Science.gov (United States)

Oethinger, Margret; Warner, Debra K; Schindler, Susan A; Kobayashi, Hideo; Bauer, Thomas W

2011-04-01

Intraoperative Gram stains have a reported low sensitivity but high specificity when used to help diagnose periprosthetic infections. In early 2008, we recognized an unexpectedly high frequency of apparent false-positive Gram stains from revision arthroplasties. The purpose of this report is to describe the cause of these false-positive test results. We calculated the sensitivity and specificity of all intraoperative Gram stains submitted from revision arthroplasty cases during a 3-month interval using microbiologic cultures of the same samples as the gold standard. Methods of specimen harvesting, handling, transport, distribution, specimen processing including tissue grinding/macerating, Gram staining, and interpretation were studied. After a test modification, results of specimens were prospectively collected for a second 3-month interval, and the sensitivity and specificity of intraoperative Gram stains were calculated. The retrospective review of 269 Gram stains submitted from revision arthroplasties indicated historic sensitivity and specificity values of 23% and 92%, respectively. Systematic analysis of all steps of the procedure identified Gram-stained but nonviable bacteria in commercial broth reagents used as diluents for maceration of periprosthetic membranes before Gram staining and culture. Polymerase chain reaction and sequencing showed mixed bacterial DNA. Evaluation of 390 specimens after initiating standardized Millipore filtering of diluent fluid revealed a reduced number of positive Gram stains, yielding 9% sensitivity and 99% specificity. Clusters of false-positive Gram stains have been reported in other clinical conditions. They are apparently rare related to diagnosing periprosthetic infections but have severe consequences if used to guide treatment. Even occasional false-positive Gram stains should prompt review of laboratory methods. Our observations implicate dead bacteria in microbiologic reagents as potential sources of false-positive Gram

Volatile metabolites from some gram-negative bacteria

DEFF Research Database (Denmark)

Schöller, Charlotte; Molin, Søren; Wilkins, Ken

1997-01-01

A survey of volatile organic compounds (VOCs) excreted from various Gram-negative bacteria (Pseudomonas spp., Serratia spp. and Enterobacter spp.) was carried out. Compounds were identified by gas chromatography-mass spectrometry. VOCs identified included dimethyl disulphide, dimethyl trisulphide...

Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections.

Science.gov (United States)

Patel, Twisha S; Kaakeh, Rola; Nagel, Jerod L; Newton, Duane W; Stevenson, James G

2017-01-01

Studies evaluating rapid diagnostic testing plus stewardship intervention have consistently demonstrated improved clinical outcomes for patients with bloodstream infections. However, the cost of implementing new rapid diagnostic testing can be significant, and such testing usually does not generate additional revenue. There are minimal data evaluating the impact of adding matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for rapid organism identification and dedicating pharmacy stewardship personnel time on the total hospital costs. A cost analysis was performed utilizing patient data generated from the hospital cost accounting system and included additional costs of MALDI-TOF equipment, supplies and personnel, and dedicated pharmacist time for blood culture review and of making interventions to antimicrobial therapy. The cost analysis was performed from a hospital perspective for 3-month blocks before and after implementation of MALDI-TOF plus stewardship intervention. A total of 480 patients with bloodstream infections were included in the analysis: 247 in the preintervention group and 233 in the intervention group. Thirty-day mortality was significantly improved in the intervention group (12% versus 21%, P cost per bloodstream infection was lower in the intervention group ($42,580 versus $45,019). Intensive care unit cost per bloodstream infection accounted for the largest share of the total costs in each group and was also lower in the intervention group ($10,833 versus $13,727). Implementing MALDI-TOF plus stewardship review and intervention decreased mortality for patients with bloodstream infections. Despite the additional costs of implementing MALDI-TOF and of dedicating pharmacy stewardship personnel time to interventions, the total hospital costs decreased by $2,439 per bloodstream infection, for an approximate annual cost savings of $2.34 million. Copyright © 2016 American Society for Microbiology.

Implementing a multifaceted intervention to decrease central line-associated bloodstream infections in SEHA (Abu Dhabi Health Services Company) intensive care units: the Abu Dhabi experience.

Science.gov (United States)

Latif, Asad; Kelly, Bernadette; Edrees, Hanan; Kent, Paula S; Weaver, Sallie J; Jovanovic, Branislava; Attallah, Hadeel; de Grouchy, Kristin K; Al-Obaidli, Ali; Goeschel, Christine A; Berenholtz, Sean M

2015-07-01

OBJECTIVE To determine whether implementation of a multifaceted intervention would significantly reduce the incidence of central line-associated bloodstream infections. DESIGN Prospective cohort collaborative. SETTING AND PARTICIPANTS Intensive care units of the Abu Dhabi Health Services Company hospitals in the Emirate of Abu Dhabi. INTERVENTIONS A bundled intervention consisting of 3 components was implemented as part of the program. It consisted of a multifaceted approach that targeted clinician use of evidence-based infection prevention recommendations, tools that supported the identification of local barriers to these practices, and implementation ideas to help ensure patients received the practices. Comprehensive unit-based safety teams were created to improve safety culture and teamwork. Finally, the measurement and feedback of monthly infection rate data to safety teams, senior leaders, and staff in participating intensive care units was encouraged. The main outcome measure was the quarterly rate of central line-associated bloodstream infections. RESULTS Eighteen intensive care units from 7 hospitals in Abu Dhabi implemented the program and achieved an overall 38% reduction in their central line-associated bloodstream infection rate, adjusted at the hospital and unit level. The number of units with a quarterly central line-associated bloodstream infection rate of less than 1 infection per 1,000 catheter-days increased by almost 40% between the baseline and postintervention periods. CONCLUSION A significant reduction in the global morbidity and mortality associated with central line-associated bloodstream infections is possible across intensive care units in disparate settings using a multifaceted intervention.

Screening of the novel colicinogenic gram-negative rods against pathogenic Escherichia coli O157:H7

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H Mushtaq

2015-01-01

Full Text Available Purpose: Escherichia coli (E. coli O157:H7 is gram-negative enteric pathogen producing different types of Shiga toxin. This bacterium is the most corporate cause of haemorrhagic colitis in human. Administration of antibiotics (particularly sulfa drugs against this pathogen is a debatable topic as this may increase the risk of uremic syndrome; especially in children and aged people. Around the world, microbiologists are in search of alternative therapeutic methods specially probiotics against this pathogen. In the present study, we have focused on the investigation of alternate bio-therapeutics (probiotics for the treatment of patients infected with E. coli O157:H7. This study is based on the identification of colicin-producing gram-negative bacteria (particularly enterobacteriaceae which can competently exclude E. coli O157:H7 from the gut of the infected individual. Materials and Methods: Hundred samples from human, animal faeces and septic tank water were analysed for nonpathogenic gram-negative rods (GNRs. Results: Out of these samples, 175 isolates of GNRs were checked for their activity against E. coli O157:H7. Only 47 isolates inhibited the growth of E. coli O157:H7, among which majority were identified as E. coli. These E. coli strains were found to be the efficient producers of colicin. Some of the closely related species i. e., Citrobacter sp, Pantoea sp. and Kluyvera sp. also showed considerable colicinogenic activity. Moreover, colicinogenic species were found to be nonhaemolytic, tolerant to acidic environment (pH 3 and sensitive to commonly used antibiotics. Conclusion: Nonhaemolytic, acid tolerant and sensitive to antibiotics suggests the possible use of these circulating endothelial cells (CEC as inexpensive and inoffensive therapeutic agent (probiotics in E. coli O157:H7 infections.

Cluster of Candida parapsilosis primary bloodstream infection in a neonatal intensive care unit

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Carmem Lúcia P. da Silva

Full Text Available Candida parapsilosis is an increasingly important bloodstream pathogen in neonatal intensive care units (NICU. We investigated a cluster of bloodstream infections in a NICU to determine whether nosocomial transmission occurred. During a 3-day period, 3 premature infants hospitalized in the same unit presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the organisms was performed by using pulsed field gel electrophoresis in a countour-clamped homogeneous electric field system. The isolate from 1 newborn could not be typed, and the isolates from the remaining 2 infants had identical patterns. All 3 cases are described. We conclude that nosocomial transmission of C. parapsilosis occurred and that neonates under intensive care may represent a risk group for this pathogen.

Cluster of Candida parapsilosis primary bloodstream infection in a neonatal intensive care unit

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Silva Carmem Lúcia P. da

2001-01-01

Full Text Available Candida parapsilosis is an increasingly important bloodstream pathogen in neonatal intensive care units (NICU. We investigated a cluster of bloodstream infections in a NICU to determine whether nosocomial transmission occurred. During a 3-day period, 3 premature infants hospitalized in the same unit presented with sepsis caused by C. parapsilosis. Electrophoretic karyotype of the organisms was performed by using pulsed field gel electrophoresis in a countour-clamped homogeneous electric field system. The isolate from 1 newborn could not be typed, and the isolates from the remaining 2 infants had identical patterns. All 3 cases are described. We conclude that nosocomial transmission of C. parapsilosis occurred and that neonates under intensive care may represent a risk group for this pathogen.

TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor

Science.gov (United States)

Jo, Yong Hun; Jung Kim, Yu; Beom Park, Ki; Hwan Seong, Jeong; Gon Kim, Soo; Park, Soyi; Young Noh, Mi; Seok Lee, Yong; Soo Han, Yeon

2017-01-01

Cactin was originally identified as an interactor of the Drosophila IκB factor Cactus and shown to play a role in controlling embryonic polarity and regulating the NF-κB signaling pathway. While subsequent studies have identified the roles for Cactin in the mammalian immune response, the immune function of Cactin in insects has not been described yet. Here, we identified a Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and characterized its functional role in innate immunity. TmCactin was highly expressed in prepupa to last instar stages, and its expression was high in the integument and Malpighian tubules of last instar larvae and adults. TmCactin was induced in larvae after infection with different pathogens and detectable within 3 hours of infection. The highest levels of TmCactin expression were detected at 9 hours post infection. TmCactin RNAi significantly decreased the survival rates of larvae after challenge with Escherichia coli and Staphylococcus aureus, but had no significant effect after challenge with Candida albicans. Furthermore, TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may serve as an important regulator of innate immunity, mediating AMP responses against both Gram-positive and Gram-negative bacteria in T. molitor. PMID:28418029

Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study.

Science.gov (United States)

Oriol, Isabel; Sabé, Núria; Simonetti, Antonella F; Lladó, Laura; Manonelles, Anna; González, Jose; Tubau, Fe; Carratalà, Jordi

2017-09-01

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time. © 2017 Steunstichting ESOT.

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals

NARCIS (Netherlands)

A. Voss (Andreas); J.A.J.W. Kluytmans (Jan); J.G. Koeleman; L. Spanjaard (Lodewijk); C.M.J.E. Vandenbroucke-Grauls (Christina); H.A. Verbrugh (Henri); M.C. Vos (Margreet); A.Y.L. Weersink (A. Y L); J.A.A. Hoogkamp-Korstanje (J. A A); J.F. Meis

1996-01-01

textabstractThe aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient

Type I and Type II mechanisms of antimicrobial photodynamic therapy: an in vitro study on gram-negative and gram-positive bacteria.

Science.gov (United States)

Huang, Liyi; Xuan, Yi; Koide, Yuichiro; Zhiyentayev, Timur; Tanaka, Masamitsu; Hamblin, Michael R

2012-08-01

Antimicrobial photodynamic therapy (APDT) employs a non-toxic photosensitizer (PS) and visible light, which in the presence of oxygen produce reactive oxygen species (ROS), such as singlet oxygen ((1) O(2), produced via Type II mechanism) and hydroxyl radical (HO(.), produced via Type I mechanism). This study examined the relative contributions of (1) O(2) and HO(.) to APDT killing of Gram-positive and Gram-negative bacteria. Fluorescence probes, 3'-(p-hydroxyphenyl)-fluorescein (HPF) and singlet oxygen sensor green reagent (SOSG) were used to determine HO(.) and (1) O(2) produced by illumination of two PS: tris-cationic-buckminsterfullerene (BB6) and a conjugate between polyethylenimine and chlorin(e6) (PEI-ce6). Dimethylthiourea is a HO(.) scavenger, while sodium azide (NaN(3)) is a quencher of (1) O(2). Both APDT and killing by Fenton reaction (chemical generation of HO(.)) were carried out on Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa). Conjugate PEI-ce6 mainly produced (1) O(2) (quenched by NaN(3)), while BB6 produced HO(.) in addition to (1) O(2) when NaN(3) potentiated probe activation. NaN(3) also potentiated HPF activation by Fenton reagent. All bacteria were killed by Fenton reagent but Gram-positive bacteria needed a higher concentration than Gram-negatives. NaN(3) potentiated Fenton-mediated killing of all bacteria. The ratio of APDT killing between Gram-positive and Gram-negative bacteria was 2 or 4:1 for BB6 and 25:1 for conjugate PEI-ce6. There was a NaN(3) dose-dependent inhibition of APDT killing using both PEI-ce6 and BB6 against Gram-negative bacteria while NaN(3) almost failed to inhibit killing of Gram-positive bacteria. Azidyl radicals may be formed from NaN(3) and HO(.). It may be that Gram-negative bacteria are more susceptible to HO(.) while Gram-positive bacteria are more susceptible to (1) O(2). The differences in Na

Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.

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Des Field

Full Text Available Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G, with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.

Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

Science.gov (United States)

Field, Des; Begley, Maire; O’Connor, Paula M.; Daly, Karen M.; Hugenholtz, Floor; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

2012-01-01

Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria. PMID:23056510

A Web-Based, Hospital-Wide Health Care-Associated Bloodstream Infection Surveillance and Classification System: Development and Evaluation.

Science.gov (United States)

Tseng, Yi-Ju; Wu, Jung-Hsuan; Lin, Hui-Chi; Chen, Ming-Yuan; Ping, Xiao-Ou; Sun, Chun-Chuan; Shang, Rung-Ji; Sheng, Wang-Huei; Chen, Yee-Chun; Lai, Feipei; Chang, Shan-Chwen

2015-09-21

Surveillance of health care-associated infections is an essential component of infection prevention programs, but conventional systems are labor intensive and performance dependent. To develop an automatic surveillance and classification system for health care-associated bloodstream infection (HABSI), and to evaluate its performance by comparing it with a conventional infection control personnel (ICP)-based surveillance system. We developed a Web-based system that was integrated into the medical information system of a 2200-bed teaching hospital in Taiwan. The system automatically detects and classifies HABSIs. In this study, the number of computer-detected HABSIs correlated closely with the number of HABSIs detected by ICP by department (n=20; r=.999 Psystem performed excellently with regard to sensitivity (98.16%), specificity (99.96%), positive predictive value (95.81%), and negative predictive value (99.98%). The system enabled decreasing the delay in confirmation of HABSI cases, on average, by 29 days. This system provides reliable and objective HABSI data for quality indicators, improving the delay caused by a conventional surveillance system.

Epidemiology, surveillance, and prevention of bloodstream infections in hemodialysis patients.

Science.gov (United States)

Patel, Priti R; Kallen, Alexander J; Arduino, Matthew J

2010-09-01

Infections cause significant morbidity and mortality in patients undergoing hemodialysis. Bloodstream infections (BSIs) are particularly problematic, accounting for a substantial number of hospitalizations in these patients. Hospitalizations for BSI and other vascular access infections appear to have increased dramatically in hemodialysis patients since 1993. These infections frequently are related to central venous catheter (CVC) use for dialysis access. Regional initiatives that have shown successful decreases in catheter-related BSIs in hospitalized patients have generated interest in replicating this success in outpatient hemodialysis populations. Several interventions have been effective in preventing BSIs in the hemodialysis setting. Avoiding the use of CVCs in favor of access types with lower associated BSI risk is among the most important. When CVCs are used, adherence to evidence-based catheter insertion and maintenance practices can positively influence BSI rates. In addition, facility-level surveillance to detect BSIs and stimulate examination of vascular access use and care practices is essential to a comprehensive approach to prevention. This article describes the current epidemiology of BSIs in hemodialysis patients and effective prevention strategies to decrease the incidence of these devastating infections.

Catheter-Related Bloodstream Infections in Adults Receiving Home Parenteral Nutrition

DEFF Research Database (Denmark)

Tribler, Siri; Brandt, Christopher F; Hvistendahl, Mark

2018-01-01

BACKGROUND: A common complication in patients receiving home parenteral nutrition (HPN) is catheter-related bloodstream infections (CRBSIs). The CRBSI incidence has been advocated as an outcome parameter assessing the quality of care. This study aimed to illustrate how the use of different CRBSI......) and European Society for Clinical Nutrition (ESPEN) CRBSI criteria. Employing a catheter-salvaging strategy, 40% of the CRBSI diagnoses were supported by the paired blood culture positivity criteria and only 6% by a positive catheter tip. In 53%, CRBSIs were categorized as a clinical or "probable CRBSI...

Patients with Central Lines - What You Need to Know to Avoid a Bloodstream Infection PSA (:60)

Centers for Disease Control (CDC) Podcasts

2011-03-01

This 60 second PSA is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.  Created: 3/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/1/2011.

Emerging Gram negative resistance to last-line antimicrobial agents fosfomycin, colistin and ceftazidime-avibactam - epidemiology, laboratory detection and treatment implications.

Science.gov (United States)

Sherry, Norelle; Howden, Benjamin

2018-04-01

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.

The structures of lipopolysaccharides from plant-associated gram-negative bacteria

DEFF Research Database (Denmark)

Molinaro, Antonio; Newman, Mari-Anne; Lanzetta, Rosa

2009-01-01

Gram-negative bacterial lipopolysaccharides (LPSs) have multiple roles in plant-microbe interactions. LPSs contribute to the low permeabilities of bacterial outer membranes, which act as barriers to protect bacteria from plant-derived antimicrobial substances. Conversely, perception of LPSs...... is an important prerequisite for any further understanding of the biological processes in plant-microbe interactions. Moreover, the LPSs from Gram-negative bacteria - especially those originating from plant-associated bacteria - are a great source of novel monosaccharides with unusual and occasionally astounding...

BACTERIAL INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS

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Elisa Balletto

2015-07-01

Full Text Available Bacterial infections are major complications after Hematopoietic Stem Cell Transplant (HSCT. They consist mainly of bloodstream infections (BSI, followed by pneumonia and gastrointestinal infections, including typhlitis and Clostridium difficile infection. Microbiological data come mostly from BSI. Coagulase negative staphylococci and Enterobacteriaceae are the most frequent pathogens causing approximately 25% of BSI each, followed by enterococci, P. aeruginosa and viridans streptococci. Bacterial pneumonia is frequent after HSCT, and Gram-negatives are predominant. Clostridium difficile infection affects approximately 15% of HSCT recipients, being more frequent in case of allogeneic than autologous HSCT. The epidemiology and the prevalence of resistant strains vary significantly between transplant centres. In some regions, multi-drug resistant Gram-negative rods are increasingly frequent. In others, vancomycin-resistant enterococci are predominant. In the era of an increasing resistance to antibiotics, the efficacy of fluoroquinolone prophylaxis and standard treatment of febrile neutropenia have been questioned. Therefore, thorough evaluation of local epidemiology is mandatory in order to decide the need for prophylaxis and the choice of the best regimen for empirical treatment of febrile neutropenia. For the latter, individualised approach has been proposed, consisting of either escalation or de-escalation strategy. De-escalation strategy is recommended is resistant bacteria should be covered upfront, mainly in patients with severe clinical presentation and previous infection or colonisation with a resistant pathogens. Non-pharmacological interventions, such as screening for resistant bacteria, applying isolation and contact precautions should be put in place in order to limit the spread of MDR bacteria. Antimicrobial stewardship program should be implemented in transplant centres.

Equipe interdisciplinar reduz infecção sanguínea relacionada ao cateter venoso central em Unidade de Terapia Intensiva Pediátrica Interdisciplinary task-force reduces catheter-related bloodstream infection in a Pediatric Intensive Care Unit

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Ricardo Vilela

2010-12-01

respectively (Phase 1 vs Phase 2 and 3; p<0.001. Gram-positive organisms were isolated in 57% of bloodstream infections in Phase 1, and 45 and 58% in Phases 2 and 3, respectively. CONCLUSIONS: The interdisciplinary educational approach and the central venous catheter insertion policies were effective to reduce central venous catheter-related bloodstream infections in the Pediatric Intensive Care Unit.

Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German Border Region-Impact of National Guidelines.

Science.gov (United States)

Köck, Robin; Siemer, Philipp; Esser, Jutta; Kampmeier, Stefanie; Berends, Matthijs S; Glasner, Corinna; Arends, Jan P; Becker, Karsten; Friedrich, Alexander W

2018-01-26

Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the Dutch-German border region, where patients are transferred between healthcare facilities located in the two different countries, because clinicians and infection control personnel must understand antibiograms indicating MDRGNB from both sides of the border and using both national guidelines. This retrospective study aimed to compare antibiograms of Gram-negative bacteria and classify them using the Dutch and German national standards for MDRGNB definition. A total of 31,787 antibiograms from six Dutch and four German hospitals were classified. Overall, 73.7% were no MDRGNB according to both guidelines. According to the Dutch and German guideline, 7772/31,787 (24.5%) and 4586/31,787 (12.9%) were MDRGNB, respectively ( p Dutch-German border, as it cannot be assumed that MDRGNB requiring special hygiene precautions are marked in the transferred antibiograms in accordance with both national guidelines.

Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria.

Science.gov (United States)

Fischer, Carol L; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

2012-03-01

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.

Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

International Nuclear Information System (INIS)

Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D’Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

2017-01-01

The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

Science.gov (United States)

Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D'Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

2017-03-01

The increasing level of antibiotic resistance in Gram-negative bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a global challenge for modern medicine. The main reason that Gram-negative bacteria are particularly challenging is the presence of an outer cell-protecting membrane, which is not present in Gram-positive species. Such an asymmetric bilayer is a highly effective barrier for polar molecules. Several protein systems are expressed in the outer membrane to control the internal concentration of both nutrients and noxious species, in particular: (i) water-filled channels that modulate the permeation of polar molecules and ions according to concentration gradients, and (ii) efflux pumps to actively expel toxic compounds. Thus, besides expressing specific enzymes for drugs degradation, Gram-negative bacteria can also resist by modulating the influx and efflux of antibiotics, keeping the internal concentration low. However, there are no direct and robust experimental methods capable of measuring the permeability of small molecules, thus severely limiting our knowledge of the molecular mechanisms that ultimately control the permeation of antibiotics through the outer membrane. This is the innovation gap to be filled for Gram-negative bacteria. This review is focused on the permeation of small molecules through porins, considered the main path for the entry of polar antibiotics into Gram-negative bacteria. A fundamental understanding of how these proteins are able to filter small molecules is a prerequisite to design/optimize antibacterials with improved permeation. The level of sophistication of modern molecular modeling algorithms and the advances in new computer hardware has made the simulation of such complex processes possible at the molecular level. In this work we aim to share our experience and perspectives in the context of a multidisciplinary extended collaboration within the IMI

Outbreak of Serratia marcescens postsurgical bloodstream infection due to contaminated intravenous pain control fluids.

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Chiang, Ping-Cherng; Wu, Tsu-Lan; Kuo, An-Jing; Huang, Yhu-Chering; Chung, Ting-Ying; Lin, Chun-Sui; Leu, Hsieh-Shong; Su, Lin-Hui

2013-09-01

Serratia marcescens is an important nosocomial pathogen causing significant outbreaks. Here we report an outbreak of bloodstream infection caused by S. marcescens at a 3500-bed hospital in Taiwan. The effective cooperative efforts of both laboratory personnel and infection control practitioners (ICPs) jointly contributed to the total control of the outbreak. A sudden increase in the isolation of S. marcescens from blood cultures was noted in the Clinical Microbiology Laboratory. The information was passed to the ICPs and an investigation was initiated. Pulsed-field gel electrophoresis was used to study the relationships among the isolates. Pulsotype A was identified in 43 (82.7%) of the 52 blood isolates studied. They were isolated from 52 patients distributed across 22 wards that were surveyed by seven ICPs. All patients had undergone surgery before the infection, and fentanyl-containing intravenous fluids were used for pain control in 43 of them. Isolates from 42 belonged to pulsotype A. Three S. marcescens isolates, all from fentanyl-containing fluids and demonstrating pulsotype A, were identified from 251 environmental cultures. All fentanyl-containing fluids that were in use were withdrawn and the outbreak was stopped. The outbreak of S. marcescens bloodstream infection apparently occurred through the use of fentanyl-containing fluids contaminated by a pulsotype A S. marcescens. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Molecular diagnosis of bloodstream infections in onco-haematology patients with PCR/ESI-MS technology.

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Jordana-Lluch, Elena; Rivaya, Belén; Marcó, Clara; Giménez, Montserrat; Quesada, Mª Dolores; Escobedo, Agustín; Batlle, Montserrat; Martró, Elisa; Ausina, Vicente

2017-02-01

Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Antimicrobial activity of metal oxide nanoparticles against Gram-positive and Gram-negative bacteria: a comparative study

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Azam A

2012-12-01

Full Text Available Ameer Azam,1,2 Arham S Ahmed,2 Mohammad Oves,3 Mohammad S Khan,3 Sami S Habib,1 Adnan Memic11Centre of Nanotechnology, King Abdulaziz University, Jeddah, Saudi Arabia; 2Centre of Excellence in Materials Science (Nanomaterials, 3Department of Agricultural Microbiology, Aligarh Muslim University, Aligarh, IndiaBackground: Nanomaterials have unique properties compared to their bulk counterparts. For this reason, nanotechnology has attracted a great deal of attention from the scientific community. Metal oxide nanomaterials like ZnO and CuO have been used industrially for several purposes, including cosmetics, paints, plastics, and textiles. A common feature that these nanoparticles exhibit is their antimicrobial behavior against pathogenic bacteria. In this report, we demonstrate the antimicrobial activity of ZnO, CuO, and Fe2O3 nanoparticles against Gram-positive and Gram-negative bacteria.Methods and results: Nanosized particles of three metal oxides (ZnO, CuO, and Fe2O3 were synthesized by a sol–gel combustion route and characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy techniques. X-ray diffraction results confirmed the single-phase formation of all three nanomaterials. The particle sizes were observed to be 18, 22, and 28 nm for ZnO, CuO, and Fe2O3, respectively. We used these nanomaterials to evaluate their antibacterial activity against both Gram-negative (Escherichia coli and Pseudomonas aeruginosa and Gram-positive (Staphylococcus aureus and Bacillus subtilis bacteria.Conclusion: Among the three metal oxide nanomaterials, ZnO showed greatest antimicrobial activity against both Gram-positive and Gram-negative bacteria used in this study. It was observed that ZnO nanoparticles have excellent bactericidal potential, while Fe2O3 nanoparticles exhibited the least bactericidal activity. The order of antibacterial activity was demonstrated to be the following: ZnO > CuO > Fe2O3

Patients with Central Lines — What You Need to Know to Avoid a Bloodstream Infection

Centers for Disease Control (CDC) Podcasts

2011-03-01

This podcast is based on the March, 2011 CDC Vital Signs report which indicates bloodstream infections in patients with central lines are largely preventable when healthcare providers use CDC-recommended infection control steps.  Created: 3/1/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/1/2011.

A randomized clinical trial on the effectiveness of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilli

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Mariana Correa Coelho Salomão

Full Text Available Abstract INTRODUCTION: We aimed to evaluate the effectiveness of a symbiotic product to decolonize the intestinal tract of patients harboring multidrug-resistant (MDR Gram-negative bacilli and to prevent nosocomial infections. METHODS: This was a randomized, double blind, placebo-controlled clinical trial, conducted in a tertiary-care university hospital. All adult hospitalized patients with a positive clinical culture and a positive rectal swab for any MDR Gram-negative bacilli were potentially eligible. Exclusion criteria were pregnancy, immunosuppression, and bowel obstruction/perforation. The intervention consisted of administering a symbiotic product (Lactobacillus bulgaricus, Lactobacillus rhamnosus, and fructo-oligosaccharides twice a day for seven days via the oral/enteral route. RESULTS: Between August 1, 2012 and December 22, 2013, 116 of 275 eligible patients were allocated to treatment (n=57 and placebo (n=59. Overall, 101 patients received at least four doses of the study products and were included in the modified intention-to-treat analysis. The primary study outcome, a negative rectal swab for MDR Gram-negative bacilli after treatment, was identified in 16.7% (8/48 and 20.7% (11/53 of patients in the experimental and placebo group, respectively (p=0.60. The secondary outcome, the combined incidence of nosocomial respiratory and urinary tract infections, was 37.5% (18/48 in the experimental group versus 22.6% (12/53 in the control group (adjusted odds ratio: 1.95, 95% confidence interval: 0.69-5.50, p=0.21. Length of stay after the beginning of the intervention, incidence of adverse events, and in-hospital mortality rates were similar in both study groups. CONCLUSIONS: Under the present study conditions, symbiotic administration was not effective for decolonizing hospitalized patients harboring MDR Gram-negative bacilli.

Plasmid-Mediated Antibiotic Resistance and Virulence in Gram-negatives: the Klebsiella pneumoniae Paradigm.

Science.gov (United States)

Ramirez, Maria S; Traglia, German M; Lin, David L; Tran, Tung; Tolmasky, Marcelo E

Plasmids harbor genes coding for specific functions including virulence factors and antibiotic resistance that permit bacteria to survive the hostile environment found in the host and resist treatment. Together with other genetic elements such as integrons and transposons, and using a variety of mechanisms, plasmids participate in the dissemination of these traits resulting in the virtual elimination of barriers among different kinds of bacteria. In this article we review the current information about physiology and role in virulence and antibiotic resistance of plasmids from the gram-negative opportunistic pathogen Klebsiella pneumoniae . This bacterium has acquired multidrug resistance and is the causative agent of serious communityand hospital-acquired infections. It is also included in the recently defined ESKAPE group of bacteria that cause most of US hospital infections.

The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

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Praveen Papareddy

Full Text Available Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2. This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis.

Science.gov (United States)

Papareddy, Praveen; Kalle, Martina; Sørensen, Ole E; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

2013-01-01

Sepsis is characterized by a dysregulated host-pathogen response, leading to high cytokine levels, excessive coagulation and failure to eradicate invasive bacteria. Novel therapeutic strategies that address crucial pathogenetic steps during infection are urgently needed. Here, we describe novel bioactive roles and therapeutic anti-infective potential of the peptide EDC34, derived from the C-terminus of tissue factor pathway inhibitor-2 (TFPI-2). This peptide exerted direct bactericidal effects and boosted activation of the classical complement pathway including formation of antimicrobial C3a, but inhibited bacteria-induced activation of the contact system. Correspondingly, in mouse models of severe Escherichia coli and Pseudomonas aeruginosa infection, treatment with EDC34 reduced bacterial levels and lung damage. In combination with the antibiotic ceftazidime, the peptide significantly prolonged survival and reduced mortality in mice. The peptide's boosting effect on bacterial clearance paired with its inhibiting effect on excessive coagulation makes it a promising therapeutic candidate for invasive Gram-negative infections.

In vitro susceptibility of gram-negative bacterial isolates to chlorhexidine gluconate.

Science.gov (United States)

Mengistu, Y; Erge, W; Bellete, B

1999-05-01

To investigate the susceptibility of clinical isolates of gram-negative bacteria to chlorhexidine gluconate. Prospective laboratory study. Tikur Anbessa Hospital, Addis Ababa, Ethiopia. Clinical specimens from 443 hospital patients. Significant number of gram negative bacteria were not inhibited by chlorhexidine gluconate (0.02-0.05%) used for antisepsis. Four hundred and forty three strains of gram-negative bacteria were isolated from Tikur Anbessa Hospital patients. Escherichia coli (31.6%) and Klebsiella pneumoniae (23%) were the most frequently isolated bacteria followed by Proteus species (13.3%), Pseudomonas species (9.2%), and Citrobacter species (6.1%). Each organism was tested to chlorhexidine gluconate (CHG), minimum inhibitory concentration (MIC) ranging from 0.0001% to 1%w/v. All Salmonella species and E. coli were inhibited by CHG, MIC or = 0.1%). Our results showed that a significant number of the gram-negative bacterial isolates were not inhibited by CHG at the concentration used for disinfection of wounds or instruments (MIC 0.02-0.05% w/v). It is therefore important to select appropriate concentration of this disinfectant and rationally use it for disinfection and hospital hygiene. Continuing follow up and surveillance is also needed to detect resistant bacteria to chlorhexidine or other disinfectants in time.

Executive summary: Diagnosis and Treatment of Catheter-Related Bloodstream Infection: Clinical Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) and the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC).

Science.gov (United States)

Chaves, Fernando; Garnacho-Montero, José; Del Pozo, José Luis; Bouza, Emilio; Capdevila, José Antonio; de Cueto, Marina; Domínguez, M Ángeles; Esteban, Jaime; Fernández-Hidalgo, Nuria; Fernández Sampedro, Marta; Fortún, Jesús; Guembe, María; Lorente, Leonardo; Paño, Jose Ramón; Ramírez, Paula; Salavert, Miguel; Sánchez, Miguel; Vallés, Jordi

2018-02-01

Catheter-related bloodstream infections (CRBSI) constitute an important cause of hospital-acquired infection associated with morbidity, mortality, and cost. The aim of these guidelines is to provide updated recommendations for the diagnosis and management of CRBSI in adults. Prevention of CRBSI is excluded. Experts in the field were designated by the two participating Societies (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica and the Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias). Short-term peripheral venous catheters, non-tunneled and long-term central venous catheters, tunneled catheters and hemodialysis catheters are covered by these guidelines. The panel identified 39 key topics that were formulated in accordance with the PICO format. The strength of the recommendations and quality of the evidence were graded in accordance with ESCMID guidelines. Recommendations are made for the diagnosis of CRBSI with and without catheter removal and of tunnel infection. The document establishes the clinical situations in which a conservative diagnosis of CRBSI (diagnosis without catheter removal) is feasible. Recommendations are also made regarding empirical therapy, pathogen-specific treatment (coagulase-negative staphylococci, Sthaphylococcus aureus, Enterococcus spp, Gram-negative bacilli, and Candida spp), antibiotic lock therapy, diagnosis and management of suppurative thrombophlebitis and local complications. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Mechanistic antimicrobial approach of extracellularly synthesized silver nanoparticles against gram positive and gram negative bacteria

Energy Technology Data Exchange (ETDEWEB)

Tamboli, Dhawal P.; Lee, Dae Sung, E-mail: daesung@knu.ac.kr

2013-09-15

Highlights: • Bacterial extracelluar enzymes stabilized the silver nanoparticles (AgNPs). • AgNPs formation was characterized by analytical techniques such as UV–vis, TEM, and FTIR. • AgNPs showed obvious antimicrobial activity against both gram positive and gram negative microorganisms. • A mechanism of AgNPs’ antimicrobial activity was proposed. -- Abstract: The development of eco-friendly and reliable processes for the synthesis of nanoparticles has attracted considerable interest in nanotechnology. In this study, an extracellular enzyme system of a newly isolated microorganism, Exiguobacterium sp. KNU1, was used for the reduction of AgNO{sub 3} solutions to silver nanoparticles (AgNPs). The extracellularly biosynthesized AgNPs were characterized by UV–vis spectroscopy, Fourier transform infra-red spectroscopy and transmission electron microscopy. The AgNPs were approximately 30 nm (range 5–50 nm) in size, well-dispersed and spherical. The AgNPs were evaluated for their antimicrobial effects on different gram negative and gram positive bacteria using the minimum inhibitory concentration method. Reasonable antimicrobial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was observed. The morphological changes occurred in all the microorganisms tested. In particular, E. coli exhibited DNA fragmentation after being treated with the AgNPs. Finally, the mechanism for their bactericidal activity was proposed according to the results of scanning electron microscopy and single cell gel electrophoresis.

Mechanistic antimicrobial approach of extracellularly synthesized silver nanoparticles against gram positive and gram negative bacteria

International Nuclear Information System (INIS)

Tamboli, Dhawal P.; Lee, Dae Sung

2013-01-01

Highlights: • Bacterial extracelluar enzymes stabilized the silver nanoparticles (AgNPs). • AgNPs formation was characterized by analytical techniques such as UV–vis, TEM, and FTIR. • AgNPs showed obvious antimicrobial activity against both gram positive and gram negative microorganisms. • A mechanism of AgNPs’ antimicrobial activity was proposed. -- Abstract: The development of eco-friendly and reliable processes for the synthesis of nanoparticles has attracted considerable interest in nanotechnology. In this study, an extracellular enzyme system of a newly isolated microorganism, Exiguobacterium sp. KNU1, was used for the reduction of AgNO 3 solutions to silver nanoparticles (AgNPs). The extracellularly biosynthesized AgNPs were characterized by UV–vis spectroscopy, Fourier transform infra-red spectroscopy and transmission electron microscopy. The AgNPs were approximately 30 nm (range 5–50 nm) in size, well-dispersed and spherical. The AgNPs were evaluated for their antimicrobial effects on different gram negative and gram positive bacteria using the minimum inhibitory concentration method. Reasonable antimicrobial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was observed. The morphological changes occurred in all the microorganisms tested. In particular, E. coli exhibited DNA fragmentation after being treated with the AgNPs. Finally, the mechanism for their bactericidal activity was proposed according to the results of scanning electron microscopy and single cell gel electrophoresis

Extended-spectrum ß-lactamases in gram negative bacteria

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Deepti Rawat

2010-01-01

Full Text Available Extended-spectrum ß-lactamases (ESBLs are a group of plasmid-mediated, diverse, complex and rapidly evolving enzymes that are posing a major therapeutic challenge today in the treatment of hospitalized and community-based patients. Infections due to ESBL producers range from uncomplicated urinary tract infections to life-threatening sepsis. Derived from the older TEM is derived from Temoniera, a patient from whom the strain was first isolated in Greece. ß-lactamases, these enzymes share the ability to hydrolyze third-generation cephalosporins and aztreonam and yet are inhibited by clavulanic acid. In addition, ESBL-producing organisms exhibit co-resistance to many other classes of antibiotics, resulting in limitation of therapeutic option. Because of inoculum effect and substrate specificity, their detection is also a major challenge. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards provide guidelines for the detection of ESBLs in Klebsiella pneumoniae, K. oxytoca, Escherichia coli and Proteus mirabilis. In common to all ESBL-detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic-resistance mechanisms in the face of the introduction of new antimicrobial agents. Thus there is need for efficient infection-control practices for containment of outbreaks; and intervention strategies, e.g., antibiotic rotation to reduce further selection and spread of these increasingly resistant pathogens.

Bacillus Cereus catheter related bloodstream infection in a patient in a patient with acute lymphblastic leukemia

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Lütfiye Öksüz

2012-01-01

Full Text Available Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related blood stream infections. Significant catheter-related bloodstream infections (CRBSI caused by Bacillus spp. are mainly due to B.cereus and have been predominantly reported in immunocompromised hosts1 . Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B.cereus in a patient with acute lymphoblastıc leukemia (ALL in Istanbul Medical Faculty was presented.A 44-year old man presented with fatigue, weight loss, epistaxis and high fever. A double-lumen Hickman–catheter (Bard 12.0 Fr, Round Dual Lumen was inserted by surgical cut-down to access the right subclavian vein which would be necessary for allogeneic stem cell transplantation. Three weeks later the patient presented with high fever and headache. Bacillus spp. was isolated from the cathether while blood culture obtained from the peripheral vein remained negative. The bacterial identification was confirmed as B.cereus using VITEK identification system It has been reported Bacillus cereus septicemia may be fatal in immunocompromised hosts despite broad-spectrum appropriate treatment10. Catheter removal is essential for prevention of recurrent bacteremia. Long-term cathater salvage should be reserved for appropriate patient group.

The target of daptomycin is absent from Escherichia coli and other gram-negative pathogens.

Science.gov (United States)

Randall, Christopher P; Mariner, Katherine R; Chopra, Ian; O'Neill, Alex J

2013-01-01

Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like Escherichia coli owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from E. coli and other Gram-negative pathogens.

Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

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Phillip S Coburn

Full Text Available The blood-retinal barrier (BRB functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE, a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3 was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB

The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.

Science.gov (United States)

Schwab, Frank; Gastmeier, Petra; Meyer, Elisabeth

2014-01-01

We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21) higher at temperatures ≥ 20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56) more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69), S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57), K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39), Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44) and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22). By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84) less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens

Marine Compounds with Therapeutic Potential in Gram-Negative Sepsis

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Irina Yermak

2013-06-01

Full Text Available This paper concerns the potential use of compounds, including lipid A, chitosan, and carrageenan, from marine sources as agents for treating endotoxemic complications from Gram-negative infections, such as sepsis and endotoxic shock. Lipid A, which can be isolated from various species of marine bacteria, is a potential antagonist of bacterial endotoxins (lipopolysaccharide (LPSs. Chitosan is a widespread marine polysaccharide that is derived from chitin, the major component of crustacean shells. The potential of chitosan as an LPS-binding and endotoxin-neutralizing agent is also examined in this paper, including a discussion on the generation of hydrophobic chitosan derivatives to increase the binding affinity of chitosan to LPS. In addition, the ability of carrageenan, which is the polysaccharide of red alga, to decrease the toxicity of LPS is discussed. We also review data obtained using animal models that demonstrate the potency of carrageenan and chitosan as antiendotoxin agents.

Antiseptic barrier cap effective in reducing central line-associated bloodstream infections : A systematic review and meta-analysis

NARCIS (Netherlands)

Voor In 't Holt, Anne F; Helder, Onno K; Vos, Margreet C; Schafthuizen, Laura; Sülz, Sandra; van den Hoogen, Agnes; Ista, Erwin

2017-01-01

BACKGROUND: Microorganisms can intraluminally access a central venous catheter via the catheter hub. The catheter hub should be appropriately disinfected to prevent central line-associated bloodstream infections (CLABSIs). However, compliance with the time-consuming manual disinfection process is

Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene

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Ryota Ito

2017-08-01

Full Text Available Fosfomycin is a decades-old antibiotic which is being revisited because of its perceived activity against many extensively drug-resistant Gram-negative pathogens. FosA proteins are Mn2+ and K+-dependent glutathione S-transferases which confer fosfomycin resistance in Gram-negative bacteria by conjugation of glutathione to the antibiotic. Plasmid-borne fosA variants have been reported in fosfomycin-resistant Escherichia coli strains. However, the prevalence and distribution of fosA in other Gram-negative bacteria are not known. We systematically surveyed the presence of fosA in Gram-negative bacteria in over 18,000 published genomes from 18 Gram-negative species and investigated their contribution to fosfomycin resistance. We show that FosA homologues are present in the majority of genomes in some species (e.g., Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa, whereas they are largely absent in others (e.g., E. coli, Acinetobacter baumannii, and Burkholderia cepacia. FosA proteins in different bacterial pathogens are highly divergent, but key amino acid residues in the active site are conserved. Chromosomal fosA genes conferred high-level fosfomycin resistance when expressed in E. coli, and deletion of chromosomal fosA in S. marcescens eliminated fosfomycin resistance. Our results indicate that FosA is encoded by clinically relevant Gram-negative species and contributes to intrinsic fosfomycin resistance.

Incidence, risk factors, microbiology of venous catheter associated bloodstream infections - A prospective study from a tertiary care hospital

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M Kaur

2015-01-01

Full Text Available Purpose : Central venous catheters (CVCs though indispensable in current medical and intensive care treatment, also puts patients at risk of catheter related infection (CRI resulting in increased morbidity and mortality. We analysed the incidence, risk factors, bacteriological profile and antimicrobial susceptibility pattern of the isolates in central venous catheter associated bloodstream infection (CVC-BSI in the intensive care unit (ICU patients and studied the formation of biofilm in CVCs. Materials and Methods: The following case control study included 115 patients with CVC in situ. Quantitative blood cultures (QBC and catheter tip cultures were performed for the diagnoses. Direct catheter staining was done for an early diagnosis by acridine orange (AO and Gram staining methods. Biofilm production in catheters was detected by ′tissue culture plate′ (TCP method. The results were analysed using the computer-based program statistical package for the social sciences (SPSS. Results : In 25/115 patients, definite diagnosis of CVC-BSI was made. The mean age was 48.44 ± 17.34 years (cases vs 40.10 ± 18.24 years (controls and the mean duration of catheterisation was 25.72 ± 8.73 days (cases vs 11.89 ± 6.38 days (controls. Local signs of infection (erythema, tenderness and oozing were found more significantly in CVC-BSI cases. The AO staining was more sensitive and Gram staining of catheters showed higher specificity. Staphylococcus aureus followed by Pseudomonas aeruginosa and non-albicans Candida were common CVC-BSI pathogens. Multidrug-resistant (MDR strains were isolated in bacterial agents of CVC-BSI. Non-albicans Candida and Enterococcus faecalis showed strong biofilm production. Conclusion : The incidence of CVC-BSI was 21.73% and the rate was 14.59 per 1000 catheter days. Prolonged ICU stay and longer catheterisation were major risk factors. S. aureus was isolated most commonly in CVC-BSI cases. The menace of multidrug resistance and

Quorum sensing signal molecules (acylated homoserine lactones) in Gram-negative fish pathogenic bacteria

DEFF Research Database (Denmark)

Bruhn, Jesper Bartholin; Dalsgaard, Inger; Nielsen, K.F.

2005-01-01

The aim of the present study was to investigate the production of quorum sensing signals (specifically acylated homoserine lactones, AHLs) among a selection of strains of Gram-negative fish bacterial pathogens. These signals are involved in the regulation of virulence factors in some human...... salmonicida and Vibrio splendidus were also positive. Aeromonas species produced N-butanoyl homoserine lactone (BHL) and N-hexanoyl homoserine lactone (HHL) and 1 additional product, whereas N-3-oxo-hexanoyl homoserine lactone (OHHL) and HHL were detected in Vibrio salmonicida. N-3-oxo-octanoyl homoserine...... lactone (OOHL) and N-3-octanoyl homoserine lactone (OHL) were detected in Y. ruckeii. AHLs were not detected from strains of Photobacterium damselae, Flavobacterium psychrophilum or Moritella viscosa. AHLs were extracted from fish infected with Y. ruckeri but not from fish infected with A. salmonicida...

Combinatorial events of insertion sequences and ICE in Gram-negative bacteria.

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Toleman, Mark A; Walsh, Timothy R

2011-09-01

The emergence of antibiotic and antimicrobial resistance in Gram-negative bacteria is incremental and linked to genetic elements that function in a so-called 'one-ended transposition' manner, including ISEcp1, ISCR elements and Tn3-like transposons. The power of these elements lies in their inability to consistently recognize one of their own terminal sequences, while recognizing more genetically distant surrogate sequences. This has the effect of mobilizing the DNA sequence found adjacent to their initial location. In general, resistance in Gram-negatives is closely linked to a few one-off events. These include the capture of the class 1 integron by a Tn5090-like transposon; the formation of the 3' conserved segment (3'-CS); and the fusion of the ISCR1 element to the 3'-CS. The structures formed by these rare events have been massively amplified and disseminated in Gram-negative bacteria, but hitherto, are rarely found in Gram-positives. Such events dominate current resistance gene acquisition and are instrumental in the construction of large resistance gene islands on chromosomes and plasmids. Similar combinatorial events appear to have occurred between conjugative plasmids and phages constructing hybrid elements called integrative and conjugative elements or conjugative transposons. These elements are beginning to be closely linked to some of the more powerful resistance mechanisms such as the extended spectrum β-lactamases, metallo- and AmpC type β-lactamases. Antibiotic resistance in Gram-negative bacteria is dominated by unusual combinatorial mistakes of Insertion sequences and gene fusions which have been selected and amplified by antibiotic pressure enabling the formation of extended resistance islands. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Prevalence of Gram-negative Pathogens and their antimicrobial ...

African Journals Online (AJOL)

The present study was conducted to find out the prevalence and spectrum of Gram negative pathogens causing bacterial meningitis and their antimicrobial susceptibility pattern in a tertiary care hospital. The cerebrospinal fluid (CSF) (3-5 ml) was collected from 638 admitted children clinically suspected of septic meningitis.

Should we use closed or open infusion containers for prevention of bloodstream infections?

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Rangel-Frausto, Manuel S; Higuera-Ramirez, Francisco; Martinez-Soto, Jose; Rosenthal, Victor D

2010-02-02

Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex) on the rate and time to onset of central line-associated bloodstream infections CLABs. An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections. A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.

A Synthetic Dual Drug Sideromycin Induces Gram-Negative Bacteria To Commit Suicide with a Gram-Positive Antibiotic.

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Liu, Rui; Miller, Patricia A; Vakulenko, Sergei B; Stewart, Nichole K; Boggess, William C; Miller, Marvin J

2018-05-10

Many antibiotics lack activity against Gram-negative bacteria because they cannot permeate the outer membrane or suffer from efflux and, in the case of β-lactams, are degraded by β-lactamases. Herein, we describe the synthesis and studies of a dual drug conjugate (1) of a siderophore linked to a cephalosporin with an attached oxazolidinone. The cephalosporin component of 1 is rapidly hydrolyzed by purified ADC-1 β-lactamase to release the oxazolidinone. Conjugate 1 is active against clinical isolates of Acinetobacter baumannii as well as strains producing large amounts of ADC-1 β-lactamase. Overall, the results are consistent with siderophore-mediated active uptake, inherent activity of the delivered dual drug, and in the presence of β-lactamases, intracellular release of the oxazolidinone upon cleavage of the cephalosporin to allow the freed oxazolidinone to inactivate its target. The ultimate result demonstrates that Gram-positive oxazolidinone antibiotics can be made to be effective against Gram-negative bacteria by β-lactamase triggered release.

[Identification of anaerobic gram-negative bacilli isolated from various clinical specimens and determination of antibiotic resistance profiles with E-test methods].

Science.gov (United States)

Demir, Cengiz; Keşli, Recep

2018-01-01

The aim of this study was to identify gram-negative anaerobic bacilli isolated from various clinical specimens that were obtained from patients with suspected anaerobic infections and to determine the antibiotic resistance profiles by using the antibiotic concentration gradient method. The study was performed in Afyon Kocatepe University Ahmet Necdet Sezer Research and Practice Hospital, Medical Microbiology Laboratory between 1 November 2014 and 30 October 2015. Two hundred and seventyeight clinical specimens accepted for anaerobic culture were enrolled in the study. All the samples were cultivated anaerobically by using Schaedler agar with 5% defibrinated sheep blood and Schaedler broth. The isolated anaerobic gram-negative bacilli were identified by using both the conventional methods and automated identification system (VITEK 2, bioMerieux, France). Antibiotic susceptibility tests were performed with antibiotic concentration gradient method (E-test, bioMerieux, France); against penicillin G, clindamycin, cefoxitin, metronidazole, moxifloxacin, imipenem, meropenem, ertapenem and doripenem for each isolate. Of the 28 isolated anaerobic gram-negative bacilli; 14 were identified as Bacteroides fragilis group, 9 were Prevotella spp., and 5 were Fusobacterium spp. The highest resistance rate was found against penicillin (78.5%) and resistance rates against clindamycin and cefoxitin were found as 17.8% and 21.4%, respectively. No resistance was found against metronidazole, moxifloxacin, imipenem, meropenem, ertapenem and doripenem. As a result, isolation and identification of anaerobic bacteria are difficult, time-consuming and more expensive when compared with the cost of aerobic culture. The rate of anaerobic bacteria isolation may be increased by obtaining the appropriate clinical specimen and appropriate transportation of these specimens. We believe that the data obtained from the study in our center may offer benefits for the follow up and treatment of infections

Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion

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Rui-Xin Wu

2017-12-01

Full Text Available Background/Purpose: Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. Methods: We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP levels, platelet (PLT, and white blood cell (WBC count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Results: Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001. Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05. No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01 in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. Conclusions: PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Keywords: Procalcitonin, Septic shock, Bloodstream infection, Burn patient, Formosa fun coast dust explosion

Gram-negative folliculitis. A rare problem or is it underdiagnosed? Case report and literature review

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Sierra-Téllez Daniela, Ponce-Olivera Rosa María, Tirado-Sánchez Andrés

2011-07-01

Full Text Available AbstractGram-negative folliculitis may be the result of prolonged antibacterial treatments in patients with acne and rosacea. It is caused by alteration of facial skin flora and the nasal mucous, a decrease of Gram-positive bacteria and a proliferation of Gram-negative bacteria (for example Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella sp. and Proteus mirabilis. It should be considered in patients with acne who have not had a clinical improvement after 3-6 months of treatment with tetracyclines. The disease is underestimated, probably because bacteriological studies are rarely requested and the increased use of oral isotretinoin for acne management. One of the most effective treatments for Gram-negative folliculitis is oral isotretinoin (0.5-1 mg / kg / day for 4-5 months. We report the case of Gram negative folliculitis successfully treated with oral isotretinoin.

Blood culture contamination with Enterococci and skin organisms: implications for surveillance definitions of primary bloodstream infections.

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Freeman, Joshua T; Chen, Luke Francis; Sexton, Daniel J; Anderson, Deverick J

2011-06-01

Enterococci are a common cause of bacteremia but are also common contaminants. In our institution, approximately 17% of positive blood cultures with enterococci are mixed with skin organisms. Such isolates are probable contaminants. The specificity of the current definition of primary bloodstream infection could be increased by excluding enterococci mixed with skin organisms. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Altered glucose kinetics in diabetic rats during Gram-negative infection

International Nuclear Information System (INIS)

Lang, C.H.; Dobrescu, C.; Bagby, G.J.; Spitzer, J.J.

1987-01-01

The present study examined the purported exacerbating effect of sepsis on glucose metabolism in diabetes. Diabetes was induced in rats by an intravenous injection of 70 or 45 mg/kg streptozotocin. The higher dose produced severe diabetes, whereas the lower dose of streptozotocin produced a miler, latent diabetes. After a chronic diabetic state had developed for 4 wk, rats had catheters implanted and sepsis induced by intraperitoneal injections of live Escherichia coli. After 24 h of sepsis the blood glucose concentration was unchanged in nondiabetics and latent diabetics, but glucose decreased from 15 to 8 mM in the septic severe diabetic group. This decrease in blood glucose was not accompanied by alterations in the plasma insulin concentration. Glucose turnover, assessed by the constant intravenous infusion of [6- 3 H]- and [U- 14 C]glucose, was elevated in the severe diabetic group, compared with either latent diabetics or nondiabetics. Sepsis increased the rate of glucose disappearance in nondiabetic rats but had no effect in either group of diabetic animals. Sepsis also failed to alter the insulinogenic index, used to estimate the insulin secretory capacity, in diabetic rats. Thus the present study suggests that the imposition of nonlethal Gram-negative sepsis on severe diabetic animals does not further impair glucose homeostasis and that the milder latent diabetes was not converted to a more severe diabetic state by the septic challenge

Antibacterial activity of crude extract of Punica granatum pericarp on pathogenic Gram-negative bacilli.

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Voravuthikunchai, S.

2005-08-01

Full Text Available The objective of this study was to investigate the effect of crude extracts of Punica granatum Linn. pericarp with 3 different solvents against pathogenic Gram-negative bacilli. Ethanolic extracts showed the antibacterial activity against all strains tested including enterohaemorrhagic Escherichia coli 4 strains (E. coli O157: H7, E. coli O26: H11, E. coli O111: NM, E. coli O22, Pseudomonas aeruginosa, Shigella boydii and Salmonella london. Inhibition zones ranged from 10.02 to 19.15 mm. Minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC ranged from 0.09 to 3.13 mg/ml and 3.13 to 25 mg/ml, respectively. Aqueous extract had low antibacterial activity while crude chloroform extracts had no effect on the growth of these strains. Ethyl acetate and n-butanol fractions of P. granatum pericarp demonstrated high activity with the best MIC and MBC values of 0.02 to 0.78 mg/ml and 0.19 to 6.25 mg/ml, respectively. As ethanolic extract of P. granatum was very effective against these pathogenic bacteria, further investigation on this plant species may provide alternative, but bioactive, medicines for the treatment of Gram-negative bacterial infection.

Bacillus Cereus catheter related bloodstream infection in a patient in a patient with acute lymphblastic leukemia

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Lütfiye Öksüz

2012-01-01

Full Text Available

Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related blood stream infections. Significant catheter-related bloodstream infections (CRBSI caused by Bacillus spp. are mainly due to B.cereus and have been predominantly reported in immunocompromised hosts¹ . Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B.cereus in a patient with acute lymphoblastıc leukemia (ALL in Istanbul Medical Faculty was presented.A 44-year old man presented with fatigue, weight loss, epistaxis and high fever. A double-lumen Hickman–catheter (Bard 12.0 Fr, Round Dual Lumen was inserted by surgical cut-down to access the right subclavian vein which would be necessary for allogeneic stem cell transplantation. Three weeks later the patient presented with high fever and headache. Bacillus spp. was isolated from the cathether while blood culture obtained from the peripheral vein remained negative. The bacterial identification was confirmed as B.cereus using VITEK identification system

It has been reported Bacillus cereus septicemia may be fatal in immunocompromised hosts despite broad-spectrum appropriate treatment¹⁰. Catheter removal is essential for prevention of recurrent bacteremia. Long-term cathater salvage should be reserved for appropriate patient group.

Quorum sensing in gram-negative bacteria

DEFF Research Database (Denmark)

Wu, H.; Song, Z.J.; Høiby, N.

2004-01-01

Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...

The warmer the weather, the more gram-negative bacteria - impact of temperature on clinical isolates in intensive care units.

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Frank Schwab

Full Text Available BACKGROUND: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. METHODS: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. RESULTS: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10-1.21 higher at temperatures ≥ 20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR=1.43; 95%CI 1.31-1.56 more frequently at high temperatures, A. baumannii 37% (IRR=1.37; 95%CI 1.11-1.69, S. maltophilia 32% (IRR=1.32; 95%CI 1.12-1.57, K. pneumoniae 26% (IRR=1.26; 95%CI 1.13-1.39, Citrobacter spp. 19% (IRR=1.19; 95%CI 0.99-1.44 and coagulase-negative staphylococci 13% (IRR=1.13; 95%CI 1.04-1.22. By contrast, S. pneumoniae 35% (IRR=0.65; 95%CI 0.50-0.84 less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR=1.03; 95%CI 1.02-1.04 increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR=1.08; 95%CI 1.05-1.12 followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. CONCLUSION: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies

A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.

Science.gov (United States)

Kollef, Marin H; Ricard, Jean-Damien; Roux, Damien; Francois, Bruno; Ischaki, Eleni; Rozgonyi, Zsolt; Boulain, Thierry; Ivanyi, Zsolt; János, Gál; Garot, Denis; Koura, Firas; Zakynthinos, Epaminondas; Dimopoulos, George; Torres, Antonio; Danker, Wayne; Montgomery, A Bruce

2017-06-01

Clinical failures in ventilator-associated pneumonia (VAP) caused by gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram-negative bacteria. There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator-free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram-negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Antibiofilm effect of Nocardiopsis sp. GRG 1 (KT235640) compound against biofilm forming Gram negative bacteria on UTIs.

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Rajivgandhi, Govindan; Vijayan, Ramachandran; Maruthupandy, Muthuchamy; Vaseeharan, Baskaralingam; Manoharan, Natesan

2018-05-01

Urinary tract infections (UTIs) are diverse public health complication and caused by range of pathogens, however mostly Gram negative bacteria cause significant life threatening risks to different populations. The prevalence rate and antimicrobial resistance among the Gram negative uropathogens alarmed significantly heighten the economic burden of these infections. In this study, we investigated the antibiofilm efficiency of Pyrrolo [1,2-a] pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl) extracted from endophytic actinomycetes Nocardiopsis sp. GRG 1 (KT235640) against P. mirabilis and E. coli. The extracted compound was characterized through TLC, HPLC, GC-MS, LC-MS and confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM). The compound, Pyrrolo [1,2-a] pyrazine-1, 4-dione, hexahydro-3-(2-methylpropyl) inhibits both bacterial biofilm formation as well as reduces the viability of preformed biofilms. Furthermore, CLSM image shows cell shrinkage, disorganized cell membrane and loss of viability. The SEM result also confirms the cell wall degradation in treated cells of the bacteria. Hence, the Pyrrolo [1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) is active against P. mirabilis and E. coli. Copyright © 2018 Elsevier Ltd. All rights reserved.

Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

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Heather Rigby

2007-01-01

Full Text Available BACKGROUND: Hematopoietic stem cell transplant (HSCT recipients are at a high risk for late bloodstream infection (BSI. Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.

Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support

DEFF Research Database (Denmark)

Tribler, Siri; Brandt, Christopher F.; Petersen, Anne H.

2017-01-01

Background: In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.Objective: This study investigates the efficacy and safety of the antimicrobial catheter lock solution, taurol...

Phenotypic and Genotypic Detection of Metallo-beta-lactamases among Imipenem-Resistant Gram Negative Isolates

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Mohammad Mohammadzadeh

2016-08-01

Full Text Available Background:   Imipenem-resistant gram negative bacteria, resulting from metallo-beta-lactamase (MBLs-producing strains have been reported to be among the important causes of nosocomial infections and of serious therapeutic problem worldwide. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all beta-lactams. The prevalence of metallo-beta-lactamase among imipenem-resistant Acinetobacter spp., Pseudomonas spp. and Enerobacteriaceae isolates is determined.Methods:   In this descriptive study 864 clinical isolates of Acinetobacter spp., Pseudomonas spp. and Enterobacteriaceae, were initially tested for imipenem susceptibility. The metallo-beta-lactamase production was detected using combined disk diffusion, double disk synergy test, and Hodge test. Then all imipenem resistant isolates were tested by PCR for imp, vim and ndm genes. Results:   Among 864 isolates, 62 (7.17 % were imipenem-resistant. Positive phonetypic test for metallo-beta-lactamase was 40 (64.5%, of which 24 (17.1% and 16 (9.2% isolates were Acinetobacter spp. and Pseudomonas spp., respectively. By PCR method 30 (48.4% of imipenem resistant Acinetobacter, and Pseudomonas isolates were positive for MBL-producing genes. None of the Enterobacteriaceae isolates were positive for metallo-beta-lactamase activity. Conclusion:   The results of this study are indicative of the growing number of nosocomial infections associated with multidrug-resistant gram negative bacteria in this region leading to difficulties in antibiotic therapy. Thereby, using of phenotypic methods can be helpful for management of this problem.

Physico-Chemical-Managed Killing of Penicillin-Resistant Static and Growing Gram-Positive and Gram-Negative Vegetative Bacteria

Science.gov (United States)

Richmond, Robert Chaffee (Inventor); Schramm, Jr., Harry F. (Inventor); Defalco, Francis G. (Inventor); Farris, III, Alex F. (Inventor)

2012-01-01

Systems and methods for the use of compounds from the Hofmeister series coupled with specific pH and temperature to provide rapid physico-chemical-managed killing of penicillin-resistant static and growing Gram-positive and Gram-negative vegetative bacteria. The systems and methods represent the more general physico-chemical enhancement of susceptibility for a wide range of pathological macromolecular targets to clinical management by establishing the reactivity of those targets to topically applied drugs or anti-toxins.

Infective Endocarditis: Identification of Catalase-Negative, Gram-Positive Cocci from Blood Cultures by Partial 16S rRNA Gene Analysis and by Vitek 2 Examination.

Science.gov (United States)

Abdul-Redha, Rawaa Jalil; Kemp, Michael; Bangsborg, Jette M; Arpi, Magnus; Christensen, Jens Jørgen

2010-01-01

Streptococci, enterococci and Streptococcus-like bacteria are frequent etiologic agents of infective endocarditis and correct species identification can be a laboratory challenge. Viridans streptococci (VS) not seldomly cause contamination of blood cultures. Vitek 2 and partial sequencing of the 16S rRNA gene were applied in order to compare the results of both methods. STRAINS ORIGINATED FROM TWO GROUPS OF PATIENTS: 149 strains from patients with infective endocarditis and 181 strains assessed as blood culture contaminants. Of the 330 strains, based on partial 16S rRNA gene sequencing results, 251 (76%) were VS strains, 10 (3%) were pyogenic streptococcal strains, 54 (16%) were E. faecalis strains and 15 (5%) strains belonged to a group of miscellaneous catalase-negative, Gram-positive cocci. Among VS strains, respectively, 220 (87,6%) and 31 (12,3%) obtained agreeing and non-agreeing identifications with the two methods with respect to allocation to the same VS group. Non-agreeing species identification mostly occurred among strains in the contaminant group, while for endocarditis strains notably fewer disagreeing results were observed.Only 67 of 150 strains in the mitis group strains obtained identical species identifications by the two methods. Most VS strains belonging to the groups of salivarius, anginosus, and mutans obtained agreeing species identifications with the two methods, while this only was the case for 13 of the 21 bovis strains. Pyogenic strains (n=10), Enterococcus faecalis strains (n=54) and a miscellaneous group of catalase-negative, Gram-positive cocci (n=15) seemed well identified by both methods, except that disagreements in identifications in the miscellaneous group of strains occurred for 6 of 15 strains.

Oral Gram-negative anaerobic bacilli as a reservoir of β-lactam resistance genes facilitating infections with multiresistant bacteria.

Science.gov (United States)

Dupin, Clarisse; Tamanai-Shacoori, Zohreh; Ehrmann, Elodie; Dupont, Anais; Barloy-Hubler, Frédérique; Bousarghin, Latifa; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne

2015-02-01

Many β-lactamases have been described in various Gram-negative bacilli (Capnocytophaga, Prevotella, Fusobacterium, etc.) of the oral cavity, belonging to class A of the Ambler classification (CepA, CblA, CfxA, CSP-1 and TEM), class B (CfiA) or class D in Fusobacterium nucleatum (FUS-1). The minimum inhibitory concentrations of β-lactams are variable and this variation is often related to the presence of plasmids or other mobile genetic elements (MGEs) that modulate the expression of resistance genes. DNA persistence and bacterial promiscuity in oral biofilms also contribute to genetic transformation and conjugation in this particular microcosm. Overexpression of efflux pumps is facilitated because the encoding genes are located on MGEs, in some multidrug-resistant clinical isolates, similar to conjugative transposons harbouring genes encoding β-lactamases. All these facts lead us to consider the oral cavity as an important reservoir of β-lactam resistance genes and a privileged place for genetic exchange, especially in commensal strictly anaerobic Gram-negative bacilli. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Prediction of lipoprotein signal peptides in Gram-negative bacteria

DEFF Research Database (Denmark)

Juncker, Agnieszka; Willenbrock, Hanni; Von Heijne, G.

2003-01-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor ...

Evaluation of an expanded microarray for detecting antibiotic resistance genes in a broad range of gram-negative bacterial pathogens.

Science.gov (United States)

Card, Roderick; Zhang, Jiancheng; Das, Priya; Cook, Charlotte; Woodford, Neil; Anjum, Muna F

2013-01-01

A microarray capable of detecting genes for resistance to 75 clinically relevant antibiotics encompassing 19 different antimicrobial classes was tested on 132 Gram-negative bacteria. Microarray-positive results correlated >91% with antimicrobial resistance phenotypes, assessed using British Society for Antimicrobial Chemotherapy clinical breakpoints; the overall test specificity was >83%. Microarray-positive results without a corresponding resistance phenotype matched 94% with PCR results, indicating accurate detection of genes present in the respective bacteria by microarray when expression was low or absent and, hence, undetectable by susceptibility testing. The low sensitivity and negative predictive values of the microarray results for identifying resistance to some antimicrobial resistance classes are likely due to the limited number of resistance genes present on the current microarray for those antimicrobial agents or to mutation-based resistance mechanisms. With regular updates, this microarray can be used for clinical diagnostics to help accurate therapeutic options to be taken following infection with multiple-antibiotic-resistant Gram-negative bacteria and prevent treatment failure.

Multidrug resistance in enteric and other gram-negative bacteria.

Science.gov (United States)

George, A M

1996-05-15

In Gram-negative bacteria, multidrug resistance is a term that is used to describe mechanisms of resistance by chromosomal genes that are activated by induction or mutation caused by the stress of exposure to antibiotics in natural and clinical environments. Unlike plasmid-borne resistance genes, there is no alteration or degradation of drugs or need for genetic transfer. Exposure to a single drug leads to cross-resistance to many other structurally and functionally unrelated drugs. The only mechanism identified for multidrug resistance in bacteria is drug efflux by membrane transporters, even though many of these transporters remain to be identified. The enteric bacteria exhibit mostly complex multidrug resistance systems which are often regulated by operons or regulons. The purpose of this review is to survey molecular mechanisms of multidrug resistance in enteric and other Gram-negative bacteria, and to speculate on the origins and natural physiological functions of the genes involved.

A resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.

Science.gov (United States)

Bush, Karen

2015-11-01

β-Lactamase inhibitors (BLIs) have played an important role in combatting β-lactam resistance in Gram-negative bacteria, but their effectiveness has diminished with the evolution of diverse and deleterious varieties of β-lactamases. In this review, a new generation of BLIs and inhibitor combinations is presented, describing epidemiological information, pharmacodynamic studies, resistance identification and current clinical status. Novel serine BLIs of major interest include the non-β-lactams of the diazabicyclo[3.2.1]octanone (DBO) series. The DBOs avibactam, relebactam and RG6080 inhibit most class A and class C β-lactamases, with selected inhibition of class D enzymes by avibactam. The novel boronic acid inhibitor RPX7009 has a similar inhibitory profile. All of these inhibitors are being developed in combinations that are targeting primarily carbapenemase-producing Gram-negative pathogens. Two BLI combinations (ceftolozane/tazobactam and ceftazidime/avibactam) were recently approved by the US Food and Drug Administration (FDA) under the designation of a Qualified Infectious Disease Product (QIDP). Other inhibitor combinations that have at least completed phase 1 clinical trials are ceftaroline fosamil/avibactam, aztreonam/avibactam, imipenem/relebactam, meropenem/RPX7009 and cefepime/AAI101. Although effective inhibitor combinations are in development for the treatment of infections caused by Gram-negative bacteria with serine carbapenemases, better options are still necessary for pathogens that produce metallo-β-lactamases (MBLs). The aztreonam/avibactam combination demonstrates inhibitory activity against MBL-producing enteric bacteria owing to the stability of the monobactam to these enzymes, but resistance is still an issue for MBL-producing non-fermentative bacteria. Because all of the inhibitor combinations are being developed as parenteral drugs, an orally bioavailable combination would also be of interest. Copyright © 2015 Elsevier B.V. and the

Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

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Simon, Arne

2016-05-01

Full Text Available Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI. Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85% have a long-term central venous access catheter in use (type Broviac or Port; CVAD. Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD- BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined.

Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

Science.gov (United States)

Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A.

2016-01-01

Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

False-Negative Rate of Gram-Stain Microscopy for Diagnosis of Septic Arthritis: Suggestions for Improvement

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Paul Stirling

2014-01-01

Full Text Available We quantify the false-negative diagnostic rate of septic arthritis using Gram-stain microscopy of synovial fluid and compare this to values reported in the peer-reviewed literature. We propose a method of improving the diagnostic value of Gram-stain microscopy using Lithium Heparin containers that prevent synovial fluid coagulation. Retrospective study of the Manchester Royal Infirmary microbiology database of patients undergoing synovial fluid Gram-stain and culture between December 2003 and March 2012 was undertaken. The initial cohort of 1896 synovial fluid analyses for suspected septic arthritis was reduced to 143 after exclusion criteria were applied. Analysis of our Gram-stain microscopy yielded 111 false-negative results from a cohort size of 143 positive synovial fluid cultures, giving a false-negative rate of 78%. We report a false-negative rate of Gram-stain microscopy for septic arthritis of 78%. Clinicians should therefore avoid the investigation until a statistically significant data set confirms its efficacy. The investigation's value could be improved by using Lithium Heparin containers to collect homogenous synovial fluid samples. Ongoing research aims to establish how much this could reduce the false-negative rate.

Gram-negative and -positive bacteria differentiation in blood culture samples by headspace volatile compound analysis.

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Dolch, Michael E; Janitza, Silke; Boulesteix, Anne-Laure; Graßmann-Lichtenauer, Carola; Praun, Siegfried; Denzer, Wolfgang; Schelling, Gustav; Schubert, Sören

2016-12-01

Identification of microorganisms in positive blood cultures still relies on standard techniques such as Gram staining followed by culturing with definite microorganism identification. Alternatively, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or the analysis of headspace volatile compound (VC) composition produced by cultures can help to differentiate between microorganisms under experimental conditions. This study assessed the efficacy of volatile compound based microorganism differentiation into Gram-negatives and -positives in unselected positive blood culture samples from patients. Headspace gas samples of positive blood culture samples were transferred to sterilized, sealed, and evacuated 20 ml glass vials and stored at -30 °C until batch analysis. Headspace gas VC content analysis was carried out via an auto sampler connected to an ion-molecule reaction mass spectrometer (IMR-MS). Measurements covered a mass range from 16 to 135 u including CO2, H2, N2, and O2. Prediction rules for microorganism identification based on VC composition were derived using a training data set and evaluated using a validation data set within a random split validation procedure. One-hundred-fifty-two aerobic samples growing 27 Gram-negatives, 106 Gram-positives, and 19 fungi and 130 anaerobic samples growing 37 Gram-negatives, 91 Gram-positives, and two fungi were analysed. In anaerobic samples, ten discriminators were identified by the random forest method allowing for bacteria differentiation into Gram-negative and -positive (error rate: 16.7 % in validation data set). For aerobic samples the error rate was not better than random. In anaerobic blood culture samples of patients IMR-MS based headspace VC composition analysis facilitates bacteria differentiation into Gram-negative and -positive.

Antimicrobial Activities of Leaf Extracts of Guava (Psidium guajava L.) on Two Gram-Negative and Gram-Positive Bacteria

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Biswas, Bipul; Rogers, Kimberly; McLaughlin, Fredrick; Yadav, Anand

2013-01-01

Aim. To determine the antimicrobial potential of guava (Psidium guajava) leaf extracts against two gram-negative bacteria (Escherichia coli and Salmonella enteritidis) and two gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) which are some of foodborne and spoilage bacteria. The guava leaves were extracted in four different solvents of increasing polarities (hexane, methanol, ethanol, and water). The efficacy of these extracts was tested against those bacteria through a well-diffusion method employing 50 μL leaf-extract solution per well. According to the findings of the antibacterial assay, the methanol and ethanol extracts of the guava leaves showed inhibitory activity against gram-positive bacteria, whereas the gram-negative bacteria were resistant to all the solvent extracts. The methanol extract had an antibacterial activity with mean zones of inhibition of 8.27 and 12.3 mm, and the ethanol extract had a mean zone of inhibition of 6.11 and 11.0 mm against B. cereus and S. aureus, respectively. On the basis of the present finding, guava leaf-extract might be a good candidate in the search for a natural antimicrobial agent. This study provides scientific understanding to further determine the antimicrobial values and investigate other pharmacological properties. PMID:24223039

Antimicrobial Activities of Leaf Extracts of Guava (Psidium guajava L. on Two Gram-Negative and Gram-Positive Bacteria

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Bipul Biswas

2013-01-01

Full Text Available Aim. To determine the antimicrobial potential of guava (Psidium guajava leaf extracts against two gram-negative bacteria (Escherichia coli and Salmonella enteritidis and two gram-positive bacteria (Staphylococcus aureus and Bacillus cereus which are some of foodborne and spoilage bacteria. The guava leaves were extracted in four different solvents of increasing polarities (hexane, methanol, ethanol, and water. The efficacy of these extracts was tested against those bacteria through a well-diffusion method employing 50 μL leaf-extract solution per well. According to the findings of the antibacterial assay, the methanol and ethanol extracts of the guava leaves showed inhibitory activity against gram-positive bacteria, whereas the gram-negative bacteria were resistant to all the solvent extracts. The methanol extract had an antibacterial activity with mean zones of inhibition of 8.27 and 12.3 mm, and the ethanol extract had a mean zone of inhibition of 6.11 and 11.0 mm against B. cereus and S. aureus, respectively. On the basis of the present finding, guava leaf-extract might be a good candidate in the search for a natural antimicrobial agent. This study provides scientific understanding to further determine the antimicrobial values and investigate other pharmacological properties.

Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

DEFF Research Database (Denmark)

Jessen, Kirstine Marie; Lindboe, Sarah Bjerre; Petersen, Anncatrine Luisa

2007-01-01

consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-alpha, (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14...... hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality. CONCLUSION: We did not find any association between TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors...... appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis....

Prevalence of Device-associated Nosocomial Infections Caused By Gram-negative Bacteria in a Trauma Intensive Care Unit in Libya

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Abdulaziz Zorgani

2015-07-01

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

Clinical and molecular epidemiology of Acinetobacter baumannii bloodstream infections in an endemic setting.

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Marchaim, Dror; Levit, Dana; Zigron, Roy; Gordon, Michal; Lazarovitch, Tsillia; Carrico, Joao A; Chalifa-Caspi, Vered; Moran-Gilad, Jacob

2017-03-01

The transmission dynamics of Acinetobacter baumannii in endemic settings, and the relation between microbial properties and patients' clinical outcomes, are yet obscure and hampered by insufficient metadata. Of 20 consecutive patients with A. baumannii bloodstream infection that were thoroughly analyzed at a single center, at least one transmission opportunity was evident for 85% of patients. This implies that patient-to-patient transmission is the major mode of A. baumannii acquisitions in health facilities. Moreover, all patients who died immediately (baumannii ST457 lineage compared with other strains.

Epidemiology and molecular characterization of multidrug-resistant Gram-negative bacteria in Southeast Asia

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Nuntra Suwantarat

2016-05-01

Full Text Available Abstract Background Multidrug-resistant Gram-negative bacteria (MDRGN, including extended-spectrum β-lactamases (ESBLs and multidrug-resistant glucose-nonfermenting Gram-negative bacilli (nonfermenters, have emerged and spread throughout Southeast Asia. Methods We reviewed and summarized current critical knowledge on the epidemiology and molecular characterization of MDRGN in Southeast Asia by PubMed searches for publications prior to 10 March 2016 with the term related to “MDRGN definition” combined with specific Southeast Asian country names (Thailand, Singapore, Malaysia, Vietnam, Indonesia, Philippines, Laos, Cambodia, Myanmar, Brunei. Results There were a total of 175 publications from the following countries: Thailand (77, Singapore (35, Malaysia (32, Vietnam (23, Indonesia (6, Philippines (1, Laos (1, and Brunei (1. We did not find any publications on MDRGN from Myanmar and Cambodia. We did not include publications related to Shigella spp., Salmonella spp., and Vibrio spp. and non-human related studies in our review. English language articles and abstracts were included for analysis. After the abstracts were reviewed, data on MDRGN in Southeast Asia from 54 publications were further reviewed and included in this study. Conclusions MDRGNs are a major contributor of antimicrobial-resistant bacteria in Southeast Asia. The high prevalence of ESBLs has been a major problem since 2005 and is possibly related to the development of carbapenem resistant organisms in this region due to the overuse of carbapenem therapy. Carbapenem–resistant Acinetobacter baumannii is the most common pathogen associated with nosocomial infections in this region followed by carbapenem-resistant Pseudomonas aeruginosa. Although Southeast Asia is not an endemic area for carbapenem-resistant Enterobacteriaceae (CRE, recently, the rate of CRE detection has been increasing. Limited infection control measures, lack of antimicrobial control, such as the presence of

Bovine mastitis caused by gram negative bacteria in Mosul

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S. Y. A. Al-Dabbagh

2012-01-01

Full Text Available A total of 90 milk samples were collected from cows with clinical and subclinical mastitis from different areas in Mosul city, in a period from October 2009 to June 2010, for the detection of gram negative bacteriological causative agents. The bacteria were identified using morphological, cultural and biochemical characteristics. thirty tow (35.3% gram negative bacterial isolates were obtained from the total count which included 14 isolates (15.5% for Escherichia coli, 7 isolates (7.7% for Klebsiella spp, 4 isolates (4.4% for Pseudomonas aeruginosa, 3 isolates (3.3% for Enterobacter aerogenes ,2 isolates for Serratia marcescens and one isolates (1.1% for each of Aeromonas hydrophila and Pasteurella multocida. Results of antibiotic sensitivity test indicated that most of these isolates were sensitive to Ciprofloxacin following by Gentamycin and Cotrimoxazole, while most of these organisms were resistant to Ampicillin, the isolates showed different percentages of sensitivity to Doxycycline, Tetracycline, Neomycin and Chloramphenicol.

Antibiotic-Resistant Gram Negative Bacilli in Meals Delivered at a General Hospital, Italy

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Maria Rosa Anna Plano

2009-01-01

Full Text Available This study aimed at detecting the presence of antibiotic-resistant Gram-negatives in samples of meals delivered at the University General Hospital of Palermo, Italy. Antibiotic resistant Gram negatives were isolated in July—September 2007 ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were submitted to susceptibility test and subtyped by random amplification of polymorphic DNA (RAPD. Forty-six of 55 (83.6% food samples and 14 of 17 (82.3% environmental swabs were culture positive for Gram negative bacilli resistant to at least one group of antibacterial drugs. A total of 134 antibiotic resistant strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non-fermenters showed frequencies as high as 97.8% of resistance to two or more groups of antibiotics and non fermenters were 28.9% resistant to more than three groups. Molecular typing detected 34 different profiles among the fermenters and 68 among the non-fermenters. Antibiotic resistance was very common among both fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns seems to support a prominent role of cross-contamination rather than a clonal expansion of a few resistant isolates. A contribution of commensal Gram negatives colonizing foods to a common bacterial resistance pool should not been overlooked.

Antibiotic-resistant gram negative bacilli in meals delivered at a general hospital, Italy.

Science.gov (United States)

Plano, Maria Rosa Anna; Di Noto, Anna Maria; Firenze, Alberto; Sciortino, Sonia; Mammina, Caterina

2009-01-01

This study aimed at detecting the presence of antibiotic-resistant Gram-negatives in samples of meals delivered at the University General Hospital of Palermo, Italy. Antibiotic resistant Gram negatives were isolated in July-September 2007 ffrom cold dishes and food contact surfaces and utensils. Bacterial strains were submitted to susceptibility test and subtyped by random amplification of polymorphic DNA (RAPD). Forty-six of 55 (83.6%) food samples and 14 of 17 (82.3%) environmental swabs were culture positive for Gram negative bacilli resistant to at least one group of antibacterial drugs. A total of 134 antibiotic resistant strains, 51 fermenters and 83 non-fermenters, were recovered. Fermenters and non-fermenters showed frequencies as high as 97.8% of resistance to two or more groups of antibiotics and non fermenters were 28.9% resistant to more than three groups. Molecular typing detected 34 different profiles among the fermenters and 68 among the non-fermenters. Antibiotic resistance was very common among both fermenters and non-fermenters. However, the wide heterogeneity of RAPD patterns seems to support a prominent role of cross-contamination rather than a clonal expansion of a few resistant isolates. A contribution of commensal Gram negatives colonizing foods to a common bacterial resistance pool should not been overlooked.

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance.

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Demetrio L Valle

Full Text Available Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC and the minimum bactericidal concentrations (MBC of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA, vancomycin-resistant Enterococcus (VRE, extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn. Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance.

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Valle, Demetrio L; Cabrera, Esperanza C; Puzon, Juliana Janet M; Rivera, Windell L

2016-01-01

Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria.

Treatment of gram-positive deep sternal wound infections in cardiac surgery -experiences with daptomycin-

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Coskun Kasim O

2011-09-01

Full Text Available Abstract The reported incidence of deep sternal wound infection (DSWI after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery. We performed an observational analysis in 23 cases of post sternotomy DSWI with gram-positive organisms February 2009 and September 2010. When the wound appeared viable and the microbiological cultures were negative, the technique of chest closure was individualised to the patient. The incidence of DSWI was 1.46%. The mean dose of daptomycin application was 4.4 ± 0.9 mg/kg/d and the average duration of the daptomycin application was 14.47 ± 7.33 days. In 89% of the patients VAC therapy was used. The duration from daptomycin application to sternal closure was 18 ± 13.9 days. The parameters of infection including, fibrinogen (p = 0.03, white blood cell count (p = 0.001 and C-reactive protein (p = 0.0001 were significantly reduced after daptomycin application. We had no mortality and wound healing was successfully achieved in all patients. Treatment of DSWI due to gram-positive organisms with a daptomycin-containing antibiotic regimen is safe, effective and promotes immediate improvement of local wound conditions. Based on these observations, daptomycin may offer a new treatment option for expediting surgical management of DSWI after cardiac surgery.

Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia.

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Fox-Dewhurst, R; Alberts, M K; Kajikawa, O; Caldwell, E; Johnson, M C; Skerrett, S J; Goodman, R B; Ruzinski, J T; Wong, V A; Chi, E Y; Martin, T R

1997-06-01

The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gram-negative pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to 1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events in the lungs and systemic circulation for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. Animals treated with low inocula had systemic changes consistent with systemic inflammatory response syndrome and cleared the bacteria and inflammatory products from the lungs. Animals treated with high inocula failed to clear bacteria from the lungs, had severe intrapulmonary inflammatory responses, and developed septic shock. Intrapulmonary leukocyte recruitment was directly related to the size of the bacterial inoculum, but lung protein accumulation was not. Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were detectable in lung lavage fluid at 4 h and declined by 24 h in animals that cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animals as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and physiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or proliferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.

Multi-location gram-positive and gram-negative bacterial protein subcellular localization using gene ontology and multi-label classifier ensemble.

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Wang, Xiao; Zhang, Jun; Li, Guo-Zheng

2015-01-01

It has become a very important and full of challenge task to predict bacterial protein subcellular locations using computational methods. Although there exist a lot of prediction methods for bacterial proteins, the majority of these methods can only deal with single-location proteins. But unfortunately many multi-location proteins are located in the bacterial cells. Moreover, multi-location proteins have special biological functions capable of helping the development of new drugs. So it is necessary to develop new computational methods for accurately predicting subcellular locations of multi-location bacterial proteins. In this article, two efficient multi-label predictors, Gpos-ECC-mPLoc and Gneg-ECC-mPLoc, are developed to predict the subcellular locations of multi-label gram-positive and gram-negative bacterial proteins respectively. The two multi-label predictors construct the GO vectors by using the GO terms of homologous proteins of query proteins and then adopt a powerful multi-label ensemble classifier to make the final multi-label prediction. The two multi-label predictors have the following advantages: (1) they improve the prediction performance of multi-label proteins by taking the correlations among different labels into account; (2) they ensemble multiple CC classifiers and further generate better prediction results by ensemble learning; and (3) they construct the GO vectors by using the frequency of occurrences of GO terms in the typical homologous set instead of using 0/1 values. Experimental results show that Gpos-ECC-mPLoc and Gneg-ECC-mPLoc can efficiently predict the subcellular locations of multi-label gram-positive and gram-negative bacterial proteins respectively. Gpos-ECC-mPLoc and Gneg-ECC-mPLoc can efficiently improve prediction accuracy of subcellular localization of multi-location gram-positive and gram-negative bacterial proteins respectively. The online web servers for Gpos-ECC-mPLoc and Gneg-ECC-mPLoc predictors are freely accessible

[Characteristic of clinical strains of gram-negative obligate anaerobes].

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Kadzielska, Joanna; Kierzkowska, Marta; Sawicka-Grzelak, Anna; Rokosz, Alicja; Łuczak, Mirosław

2007-01-01

The aim of the study was to assess prevalence and antibiotic susceptibility profiles ofGram-negative strictly anaerobic bacteria isolated from clinical specimens taken from hospitalized patients in 2005-2006. Biochemical identification and antibiotic susceptibility were done in an automated system ATB Expression (bioMerieux sa). From 12262 specimens examined 867 strains of obligate anaerobes were isolated. Gram-negative strictly anaerobic bacteria were cultured in number of 138 strains (15,9%). All cultures were performed on Columbia agar and Schaedler agar media (bioMerieux sa) supplemented with 5% sheep blood and incubated at 37 degrees C for 48-120 h in 85% N2, 10% H2, 5% CO2. Most frequently isolated was Bacteroides spp. (41,3%). For this group beta-lactamase activity was evaluated by using nitrocefin disc test (Cefinase BBL, Becton Dickinson and Co., Cockeysville, MD, USA). Production of ESBLs was detected with the use of two disc diffusion methods: the double-disc synergy test (DDST) according to Jarlier et al. and the diagnostic disc (DD) test according to Appleton. ESBLs were produced by 5,3% strains of Bacteroides spp. For all Bacteroides spp. strains MIC values were determined by gradient diffusion method Etest (AB BIODISK, Sweden). ESBLs and MIC were performed on Wilkins-Chalgren solid medium supplemented with 5% sheep blood (Difco Lab., USA) and all plates were incubated at 35 degrees C for 48 hours in 85% N2, 10% H2, 5% CO2. Most Gram-negative obligate anaerobes isolated from clinical specimens are still susceptible to imipenem (100%), metronidazole (99,3%) and beta-lactam antibiotics with beta-lactamase inhibitors: piperacillin/tazobactam (99,3%), ticarcillin/clavulanate (99.3%), amoxicillin/clavulanate (97.8%).

Comparison of flomoxef with latamoxef in the treatment of sepsis and/or Gram-negative bacteremia in adult patients.

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Chen, Y C; Hung, C C; Lin, S F; Chang, S C; Hsieh, W C

1996-05-01

The safety and efficacy of flomoxef and latamoxef were compared in the treatment of hospitalized patients with sepsis and/or Gram-negative bacteremia in a prospective, open-labelled clinical trial. Patients were randomized to receive 1 to 2 g intravenous doses of either flomoxef every 6 to 12 h, or latamoxef every 8 to 12 h. Data from 21 patients given flomoxef and 23 patients given latamoxef were included in the evaluation of efficacy. Flomoxef produced clinical cure and satisfactory microbiological responses in 85.7% and 100% of patients, respectively. These results were similar to those obtained with latamoxef (87% and 100%, respectively). In addition, no significant difference was found in mean age, sex, severity of infection, distribution of pathogens and focus of infection between the two groups. However, the flomoxef group included more patients with ultimately fatal diseases. Six patients given flomoxef and two patients given latamoxef developed superinfections caused by yeast, enterococci and Pseudomonas aeruginosa in the urinary tract. Mild and reversible adverse reactions probably related to flomoxef and latamoxef were noted in 14.3% and 13% of patients, respectively. The results of this study demonstrated that flomoxef is a safe and effective antimicrobial agent in the treatment of patients with sepsis and/or Gram-negative bacteremia.

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents.

Science.gov (United States)

Sader, Helio S; Jones, Ronald N; Stilwell, Matthew G; Dowzicky, Michael J; Fritsche, Thomas R

2005-07-01

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

APSIC guide for prevention of Central Line Associated Bloodstream Infections (CLABSI

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Moi Lin Ling

2016-05-01

Full Text Available Abstract This document is an executive summary of the APSIC Guide for Prevention of Central Line Associated Bloodstream Infections (CLABSI. It describes key evidence-based care components of the Central Line Insertion and Maintenance Bundles and its implementation using the quality improvement methodology, namely the Plan-Do-Study-Act (PDSA methodology involving multidisciplinary process and stakeholders. Monitoring of improvement over time with timely feedback to stakeholders is a key component to ensure the success of implementing best practices. A surveillance program is recommended to monitor outcomes and adherence to evidence-based central line insertion and maintenance practices (compliance rate and identify quality improvement opportunities and strategically targeting interventions for the reduction of CLABSI.

Epidemiology, clinical characteristics and treatment outcomes of healthcare- associated methicillin-resistant Staphylococcus aureus BLOODSTREAM infections at Chiang Mai University Hospital: a retrospective study.

Science.gov (United States)

Chaiwarith, Romanee; Pacharasupal, Phongsathon; Sirisanthana, Thira

2014-07-01

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) varies widely by region and healthcare setting. The prevalence of MRSA among S. aureus bloodstream infections increased from 23% in 2007 to 43% in 2011 at our hospital. We conducted this retrospective study among patients with MRSA to determine mortality rate of MRSA bloodstream infections (BSIs) and the risk factors for death in those patients at Chiang Mai University Hospital from January 1, 2007 to December 31, 2011. One hundred seventy-nine patients with 184 episodes of MRSA BSIs were enrolled. Ninety-eight patients (54.8%) were male and the mean age was 53.4±25.3 years. The median length of time from admission to diagnosis was 27.5 days (IQR 15, 43.5). One-hundred six patients had BSI with other sites of infection: pneumonia (78 episodes, 42.4%), skin and soft tissue infections (15 episodes, 8.2%), urinary tract infections (13 episodes, 7.1%) and infective endocarditis (4 episodes, 2.2%). The mortality rate was 53.1% (95 patients). Risk factors for death on multivariate analysis were: concurrent pulmonary infection (OR 2.65; 95% CI: 1.27-5.51, p=0.009), having a central venous catheter (OR 8.85; 95% CI: 2.31-33.88, p=0.001), having a urinary catheter (OR 8.52; 95% CI: 2.60-27.89, p < 0.001) and having a prothrombin time longer than 1.5 times the upper limit of normal (OR 3.85; 95% CI: 1.68-8.81, p=0.001). MRSA bloodstream infections caused significant mortality particularly among those patients with concurrent pulmonary infections.

Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch–German Border Region—Impact of National Guidelines

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Robin Köck

2018-01-01

Full Text Available Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB is a public health priority. However, the definition of MDRGNB applied for planning infection prevention measures such as barrier precautions differs depending on national guidelines. This is particularly relevant in the Dutch–German border region, where patients are transferred between healthcare facilities located in the two different countries, because clinicians and infection control personnel must understand antibiograms indicating MDRGNB from both sides of the border and using both national guidelines. This retrospective study aimed to compare antibiograms of Gram-negative bacteria and classify them using the Dutch and German national standards for MDRGNB definition. A total of 31,787 antibiograms from six Dutch and four German hospitals were classified. Overall, 73.7% were no MDRGNB according to both guidelines. According to the Dutch and German guideline, 7772/31,787 (24.5% and 4586/31,787 (12.9% were MDRGNB, respectively (p < 0.0001. Major divergent classifications were observed for extended-spectrum β-lactamase (ESBL -producing Enterobacteriaceae, non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The observed differences show that medical staff must carefully check previous diagnostic findings when patients are transferred across the Dutch–German border, as it cannot be assumed that MDRGNB requiring special hygiene precautions are marked in the transferred antibiograms in accordance with both national guidelines.

In vitro activity of tigecycline and colistin against A. baumannii clinical bloodstream isolates during an 8-year period.

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Spiliopoulou, Anastasia; Jelastopulu, Eleni; Vamvakopoulou, Sofia; Bartzavali, Christina; Kolonitsiou, Fevronia; Anastassiou, Evangelos D; Christofidou, Myrto

2015-10-01

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.

Rapid, highly sensitive detection of Gram-negative bacteria with lipopolysaccharide based disposable aptasensor.

Science.gov (United States)

Zhang, Jian; Oueslati, Rania; Cheng, Cheng; Zhao, Ling; Chen, Jiangang; Almeida, Raul; Wu, Jayne

2018-07-30

Gram-negative bacteria are one of the most common microorganisms in the environment. Their differential detection and recognition from Gram-positive bacteria has been attracting much attention over the years. Using Escherichia coli (E. coli) as a model, we demonstrated on-site detection of Gram-negative bacteria by an AC electrokinetics-based capacitive sensing method using commercial microelectrodes functionalized with an aptamer specific to lipopolysaccharides. Dielectrophoresis effect was utilized to enrich viable bacteria to the microelectrodes rapidly, achieving a detection limit of 10 2 cells/mL within a 30 s' response time. The sensor showed a negligible response to Staphylococcus aureus (S. aureus), a Gram-positive species. The developed sensor showed significant advantages in sensitivity, selectivity, cost, operation simplicity, and response time. Therefore, this sensing method has shown great application potential for environmental monitoring, food safety, and real-time diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Community-Onset Bloodstream Infection during the ‘After Hours’ Is not Associated with an increased Risk for Death

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Kevin B Laupland

2012-01-01

Full Text Available BACKGROUND/OBJECTIVE: Patients admitted to hospital during the ‘after hours’ (weekends and evenings may be at increased risk for adverse outcome. The objective of the present study was to assess whether community-onset bloodstream infections presenting in the after hours are associated with death.

Clinical and Laboratory Characteristics of Patients with Nontuberculous Mycobacterium Bloodstream Infection in a Tertiary Referral Hospital in Beijing, China

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Sai-Nan Bian

2016-01-01

Conclusions: We reported all cases in our hospital diagnosed with bloodstream NTM infection that was rarely reported. In this group of patients, patients usually had a high fever and could have multiple organ involvements. All patients with poor prognosis had underlying diseases.

A pathway closely related to the (D)-tagatose pathway of gram-negative enterobacteria identified in the gram-positive bacterium Bacillus licheniformis.

Science.gov (United States)

Van der Heiden, Edwige; Delmarcelle, Michaël; Lebrun, Sarah; Freichels, Régine; Brans, Alain; Vastenavond, Christian M; Galleni, Moreno; Joris, Bernard

2013-06-01

We report the first identification of a gene cluster involved in d-tagatose catabolism in Bacillus licheniformis. The pathway is closely related to the d-tagatose pathway of the Gram-negative bacterium Klebsiella oxytoca, in contrast to the d-tagatose 6-phosphate pathway described in the Gram-positive bacterium Staphylococcus aureus.

A Pathway Closely Related to the d-Tagatose Pathway of Gram-Negative Enterobacteria Identified in the Gram-Positive Bacterium Bacillus licheniformis

OpenAIRE

Van der Heiden, Edwige; Delmarcelle, Michaël; Lebrun, Sarah; Freichels, Régine; Brans, Alain; Vastenavond, Christian M.; Galleni, Moreno; Joris, Bernard

2013-01-01

We report the first identification of a gene cluster involved in d-tagatose catabolism in Bacillus licheniformis. The pathway is closely related to the d-tagatose pathway of the Gram-negative bacterium Klebsiella oxytoca, in contrast to the d-tagatose 6-phosphate pathway described in the Gram-positive bacterium Staphylococcus aureus.

Brazilian experience in EU-CORE: daptomycin registry and treatment of serious Gram-positive infections

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Artur Timerman

Full Text Available OBJECTIVES: To collect data about non-controlled prescribing use of daptomycin and its impact among Brazilian patients with serious Gram positive bacterial infection, as well as the efficacy and safety outcomes. MATERIALS AND METHODS: This is a multi-center, retrospective, non-interventional registry (August 01, 2009 to June 30, 2011 to collect data on 120 patients (44 patients in the first year and 76 patients in the second year who had received at least one dose of commercial daptomycin in Brazil for the treatment of serious Gram-positive bacterial infection. RESULTS: Right-sided endocarditis (15.8%, complicated skin and soft tissue infections (cSSTIwound (15.0% and bacteremia-catheter-related (14.2% were the most frequent primary infections; lung (21.7% was the most common site for infection. Daptomycin was used empirically in 76 (63.3% patients, and methicillin-resistant Staphylococcus aureus (MRSA was the most common suspected pathogen (86.1%. 82.5% of the cultures were obtained prior to or shortly after initiation of daptomycin therapy. Staphylococcus spp. - coagulase negative, MRSA, and methicillin-susceptible S. aureus were the most frequently identified pathogens (23.8%, 23.8% and 12.5%, respectively. The most common daptomycin dose administered for bacteremia and cSSTI was 6 mg/kg (30.6% and 4 mg/kg (51.7%, respectively. The median duration of inpatient daptomycin therapy was 14 days. Most patients (57.1% did not receive daptomycin while in intensive care unit. Carbapenem (22.5% was the most commonly used antibiotic concomitantly. The patients showed clinical improvement after two days (median following the start of daptomycin therapy. The clinical success rate was 80.8% and the overall rate of treatment failure was 10.8%. The main reasons for daptomycin discontinuation were successful end of therapy (75.8%, switched therapy (11.7%, and treatment failure (4.2%. Daptomycin demonstrated a favorable safety and tolerability profile

Distribution and Antimicrobial Susceptibility Pattern of Gram Negative Bacteria Causing Urinary Tract Infection (UTI and Detection New Delhi Metallo-beta-lactamase-1 (NDM-1 Producing Isolates in Ahwaz

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Parviz Afrugh

2016-04-01

Full Text Available Background: Urinary tract infection (UTI is the commonest bacterial infectious disease in worldwide (especially in developing countries with a high rate of morbidity and financial cost. The management of UTI infections has been jeopardized by increase in immergence of antimicrobial drug resistance. Knowledge of the local bacterial etiology and susceptibility patterns is required to trace any change that might have occurred in time so that updated recommendation for optimal empirical therapy of UTI can be made. The aim of this investigation was distribution and antimicrobial susceptibility pattern of gram negative bacteria causing urinary tract infection (UTI and detection NDM-1 (new-delhi-metallo-beta-lactamase-1 producing isolates in Ahwaz. Materials and Methods: This cross-sectional study was done during a period of one year from April 2013 to March 2014. Clean catch midstream urine samples were collected from suspected patients to UTI. The isolates were identified based on morphological and biochemical testes. Culture was performed on routine microbiological media. Susceptibility testing was performed according CLSI (2013 guidelines. Detection of carbapenemase producing isolates was performed by modified hodge test (MHT. Metallo-beta-lactamase isolates were detected by imipenem-EDTA combined disc test (CDT. Results: In this study 708 gram negative organisms were isolated from urine samples. E.coli was the most common isolated bacteria (67% followed by Klebsiella spp. (26.5% and Enterobacter spp. (2.5%. In antibiotic susceptibility testing more than 90% of isolates were sensitive to tetracycline, ceftazidime, meropenem, amikacin, cefotaxime, imipenem, and cefepime. Isolates were more resistant to cephalothin (32%, co-trimoxazol (30.5%, and nalidixic acid (25%. Conclusion: In our results isolated organisms from outpatients showed very high sensitivity to common antibiotics. Continuous and regular monitoring of susceptibility pattern of

A Pathway Closely Related to the d-Tagatose Pathway of Gram-Negative Enterobacteria Identified in the Gram-Positive Bacterium Bacillus licheniformis

Science.gov (United States)

Van der Heiden, Edwige; Lebrun, Sarah; Freichels, Régine; Brans, Alain; Vastenavond, Christian M.; Galleni, Moreno; Joris, Bernard

2013-01-01

We report the first identification of a gene cluster involved in d-tagatose catabolism in Bacillus licheniformis. The pathway is closely related to the d-tagatose pathway of the Gram-negative bacterium Klebsiella oxytoca, in contrast to the d-tagatose 6-phosphate pathway described in the Gram-positive bacterium Staphylococcus aureus. PMID:23524682

Non-oral gram-negative facultative rods in chronic periodontitis microbiota

NARCIS (Netherlands)

van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadnach; Rams, Thomas E

OBJECTIVE: The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. METHODS:

Rapid and reliable identification of Gram-negative bacteria and Gram-positive cocci by deposition of bacteria harvested from blood cultures onto the MALDI-TOF plate.

OpenAIRE

Barnini, S; Ghelardi, Emilia; Brucculeri, V; Morici, Paola; Lupetti, Antonella

2015-01-01

Background Rapid identification of the causative agent(s) of bloodstream infections using the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) methodology can lead to increased empirical antimicrobial therapy appropriateness. Herein, we aimed at establishing an easier and simpler method, further referred to as the direct method, using bacteria harvested by serum separator tubes from positive blood cultures and placed onto the polished steel target plate for rapid identif...

Update on the taxonomy and the clinical and laboratory characteristics of pigmented anaerobic gram-negative rods.

Science.gov (United States)

Jousimies-Somer, H R

1995-06-01

Pigmented anaerobic gram-negative rods are currently categorized as 17 species distributed in three genera: Prevotella, Porphyromonas, and Bacteroides. These organisms are often encountered in clinical specimens but are also found as part of the indigenous flora on various mucosal surfaces. Several studies are presently assessing the association of individual species with health and disease. For example, Porphyromonas gingivalis and Porphyromonas endodontalis are key putative pathogens in adult periodontitis and root canal infections, respectively. Porphyromonas asaccharolytica is prevalent in extraoral infections. The Porphyromonas species of animal origin have been isolated from infected bite wounds in humans. Isolates closely resembling Bacteroides levii have been recovered from various types of human infections. According to preliminary reports, Prevotella intermedia tends to be associated more often with periodontal disease than with a healthy oral cavity. In the laboratory, enzyme profiling facilitates the identification of these pigmented rods. Beta-Lactamase production is more common among prevotella species (30%-50%) than among Porphyromonas species (< 10%).

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

Science.gov (United States)

Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Coordinated Molecular Cross-Talk between Staphylococcus aureus, Endothelial Cells and Platelets in Bloodstream Infection

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Carolina D. Garciarena

2015-12-01

Full Text Available Staphylococcus aureus is an opportunistic pathogen often carried asymptomatically on the human body. Upon entry to the otherwise sterile environment of the cardiovascular system, S. aureus can lead to serious complications resulting in organ failure and death. The success of S. aureus as a pathogen in the bloodstream is due to its ability to express a wide array of cell wall proteins on its surface that recognise host receptors, extracellular matrix proteins and plasma proteins. Endothelial cells and platelets are important cells in the cardiovascular system and are a major target of bloodstream infection. Endothelial cells form the inner lining of a blood vessel and provide an antithrombotic barrier between the vessel wall and blood. Platelets on the other hand travel throughout the cardiovascular system and respond by aggregating around the site of injury and initiating clot formation. Activation of either of these cells leads to functional dysregulation in the cardiovascular system. In this review, we will illustrate how S. aureus establish intimate interactions with both endothelial cells and platelets leading to cardiovascular dysregulation.

Cytokine profile in severe gram-positive and gram-negative abdominal sepsis

Science.gov (United States)

Surbatovic, Maja; Popovic, Nada; Vojvodic, Danilo; Milosevic, Ivan; Acimovic, Gordana; Stojicic, Milan; Veljovic, Milic; Jevdjic, Jasna; Djordjevic, Dragan; Radakovic, Sonja

2015-01-01

Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors. PMID:26079127

Characterising health care-associated bloodstream infections in public hospitals in Queensland, 2008-2012.

Science.gov (United States)

Si, Damin; Runnegar, Naomi; Marquess, John; Rajmokan, Mohana; Playford, Elliott G

2016-04-18

To describe the epidemiology and rates of all health care-associated bloodstream infections (HA-BSIs) and of specific HA-BSI subsets in public hospitals in Queensland. Standardised HA-BSI surveillance data were collected in 23 Queensland public hospitals, 2008-2012. HA-BSIs were prospectively classified in terms of place of acquisition (inpatient, non-inpatient); focus of infection (intravascular catheter-associated, organ site focus, neutropenic sepsis, or unknown focus); and causative organisms. Inpatient HA-BSI rates (per 10,000 patient-days) were calculated. There were 8092 HA-BSIs and 9418 causative organisms reported. Inpatient HA-BSIs accounted for 79% of all cases. The focus of infection in 2792 cases (35%) was an organ site, intravascular catheters in 2755 (34%; including 2240 central line catheters), neutropenic sepsis in 1063 (13%), and unknown in 1482 (18%). Five per cent (117 of 2240) of central line-associated BSIs (CLABSIs) were attributable to intensive care units (ICUs). Eight groups of organisms provided 79% of causative agents: coagulase-negative staphylococci (18%), Staphylococcus aureus (15%), Escherichia coli (11%), Pseudomonas species (9%), Klebsiella pneumoniae/oxytoca (8%), Enterococcus species (7%), Enterobacter species (6%), and Candida species (5%). The overall inpatient HA-BSI rate was 6.0 per 10,000 patient-days. The rates for important BSI subsets included: intravascular catheter-associated BSIs, 1.9 per 10,000 patient-days; S. aureus BSIs, 1.0 per 10,000 patient-days; and methicillin-resistant S. aureus BSIs, 0.3 per 10,000 patient-days. The rate of HA-BSIs in Queensland public hospitals is lower than reported by similar studies elsewhere. About one-third of HA-BSIs are attributable to intravascular catheters, predominantly central venous lines, but the vast majority of CLABSIs are contracted outside ICUs. Different sources of HA-BSIs require different prevention strategies.

Surface-Exposed Lipoproteins: An Emerging Secretion Phenomenon in Gram-Negative Bacteria.

Science.gov (United States)

Wilson, Marlena M; Bernstein, Harris D

2016-03-01

Bacterial lipoproteins are hydrophilic proteins that are anchored to a cell membrane by N-terminally linked fatty acids. It is widely believed that nearly all lipoproteins produced by Gram-negative bacteria are either retained in the inner membrane (IM) or transferred to the inner leaflet of the outer membrane (OM). Lipoproteins that are exposed on the cell surface have also been reported but are generally considered to be rare. Results from a variety of recent studies, however, now suggest that the prevalence of surface-exposed lipoproteins has been underestimated. In this review we describe the evidence that the surface exposure of lipoproteins in Gram-negative bacteria is a widespread phenomenon and discuss possible mechanisms by which these proteins might be transported across the OM. Published by Elsevier Ltd.

Amplifiable DNA from Gram-negative and Gram-positive bacteria by a low strength pulsed electric field method

Science.gov (United States)

Vitzthum, Frank; Geiger, Georg; Bisswanger, Hans; Elkine, Bentsian; Brunner, Herwig; Bernhagen, Jürgen

2000-01-01

An efficient electric field-based procedure for cell disruption and DNA isolation is described. Isoosmotic suspensions of Gram-negative and Gram-positive bacteria were treated with pulsed electric fields of Pulses had an exponential decay waveform with a time constant of 3.4 µs. DNA yield was linearly dependent on time or pulse number, with several thousand pulses needed. Electrochemical side-effects and electrophoresis were minimal. The lysates contained non-fragmented DNA which was readily amplifiable by PCR. As the method was not limited to samples of high specific resistance, it should be applicable to physiological fluids and be useful for genomic and DNA diagnostic applications. PMID:10734214

Comparative activity of tigecycline and tetracycline on Gram-negative and Gram-positive bacteria revealed by a multicentre study in four North European countries

DEFF Research Database (Denmark)

Nilsson, Lennart E; Frimodt-Møller, Niels; Vaara, Martti

2011-01-01

This study involves a multicentre surveillance of tigecycline and tetracycline activity against Gram-negative and Gram-positive bacteria from primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs) in Denmark (n = 9), Finland (n = 10), Norway (n = 7) and Sweden (n...

Mucosal barrier injury laboratory-confirmed bloodstream infection: results from a field test of a new National Healthcare Safety Network definition.

Science.gov (United States)

See, Isaac; Iwamoto, Martha; Allen-Bridson, Kathy; Horan, Teresa; Magill, Shelley S; Thompson, Nicola D

2013-08-01

To assess challenges to implementation of a new National Healthcare Safety Network (NHSN) surveillance definition, mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI). Multicenter field test. Selected locations of acute care hospitals participating in NHSN central line-associated bloodstream infection (CLABSI) surveillance. Hospital staff augmented their CLABSI surveillance for 2 months to incorporate MBI-LCBI: a primary bloodstream infection due to a selected group of organisms in patients with either neutropenia or an allogeneic hematopoietic stem cell transplant with gastrointestinal graft-versus-host disease or diarrhea. Centers for Disease Control and Prevention (CDC) staff reviewed submitted data to verify whether CLABSIs met MBI-LCBI criteria and summarized the descriptive epidemiology of cases reported. Eight cancer, 2 pediatric, and 28 general acute care hospitals including 193 inpatient units (49% oncology/bone marrow transplant [BMT], 21% adult ward, 20% adult critical care, 6% pediatric, 4% step-down) conducted field testing. Among 906 positive blood cultures reviewed, 282 CLABSIs were identified. Of the 103 CLABSIs that also met MBI-LCBI criteria, 100 (97%) were reported from oncology/BMT locations. Agreement between hospital staff and CDC classification of reported CLABSIs as meeting the MBI-LCBI definition was high (90%; κ = 0.82). Most MBI-LCBIs (91%) occurred in patients meeting neutropenia criteria. Some hospitals indicated that their laboratories' methods of reporting cell counts prevented application of neutropenia criteria; revised neutropenia criteria were created using data from field testing. Hospital staff applied the MBI-LCBI definition accurately. Field testing informed modifications for the January 2013 implementation of MBI-LCBI in the NHSN.

The resveratrol tetramer (--hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.

Directory of Open Access Journals (Sweden)

Caroline E Zetterström

Full Text Available Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (--hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (--hopeaphenol in three different gram-negative bacteria. (--Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (--hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

Gram staining.

Science.gov (United States)

Coico, Richard

2005-10-01

Named after Hans Christian Gram who developed the method in 1884, the Gram stain allows one to distinguish between Gram-positive and Gram-negative bacteria on the basis of differential staining with a crystal violet-iodine complex and a safranin counterstain. The cell walls of Gram-positive organisms retain this complex after treatment with alcohol and appear purple, whereas gram-negative organisms decolorize following such treatment and appear pink. The method described here is useful for assessing bacterial contamination of tissue culture samples or for examining the Gram stain status and morphological features of bacteria isolated from mixed or isolated bacterial cultures.

Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion.

Science.gov (United States)

Wu, Rui-Xin; Chiu, Chih-Chien; Lin, Tzu-Chao; Yang, Ya-Sung; Lee, Yi; Lin, Jung-Chung; Chang, Feng-Yee

2017-12-01

Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT) with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP) levels, platelet (PLT), and white blood cell (WBC) count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001). Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05). No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01) in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Copyright © 2017. Published by Elsevier B.V.

Candidatus Renichlamydia lutjani, a Gram-negative bacterium in internal organs of blue striped snapper Lutjanus kasmira from Hawaii

Science.gov (United States)

Corsaro, Daniele; Work, Thierry M.

2012-01-01

The blue-striped snapper Lutjanus kasmira (Perciformes, Lutjanidae) are cosmopolitan in the Indo-Pacific but were introduced into Oahu, Hawaii, USA, in the 1950s and have since colonized most of the archipelago. Studies of microparasites in blue-striped snappers from Hawaii revealed chlamydia-like organisms (CLO) infecting the spleen and kidney, characterized by intracellular basophilic granular inclusions containing Gram-negative and Gimenez-positive bacteria similar in appearance to epitheliocysts when seen under light microscopy. We provide molecular evidence that CLO are a new member of Chlamydiae, i.e. Candidatus Renichlamydia lutjani, that represents the first reported case of chlamydial infection in organs other than the gill in fishes.

NDM 1 Gene Carrying Gram negative Bacteria Isolated from Rats ...

African Journals Online (AJOL)

In this study, we screened 56 Gram negative bacteria comprising: 3 isolates of Enterobacter ludwigii, 30 Pseudomonas aeruginosa, 22 Proteus mirabilis, and 1 Aeromonas caviae isolated from oral cavity and rectum of rats captured from commercial poultry houses in Ibadan, Oyo State, Nigeria that were resistant to at least ...

[Epidemiology of nosocomial infections in neonates].

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Lachassinne, E; Letamendia-Richard, E; Gaudelus, J

2004-03-01

Epidemiology of nosocomial infections in neonates has to be described according to our definitions (early onset GBS diseases excluded) and according to levels of care. Nosocomial risk exists in maternity departments (3% in postnatal beds), incidence rates are 7.5-12.7% or 1.3-8.5 per 1000 days in neonatal care units and 14.2% or 11.7 per 1000 days in neonatal intensive care units (NICU). Gram-positive cocci bloodstream infections are the most common nosocomial infections in NICU but viral gastroenteritis are more frequent in neonatal care units. Risk factors are low birthweight, small gestational age and intravascular catheter in NICU, and for viral nosocomial infections, visits and winter outbreaks.

Staphylococcus species and their Methicillin-Resistance in 7424 Blood Cultures for Suspected Bloodstream Infections

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Ariana ALMAŞ

2011-06-01

Full Text Available Objectives: The aim of this study was to evaluate the distribution of Staphylococcus species in bloodstream infections and to assess their susceptibility to methicillin. Material and Methods: Between January 1st 2008 - December 31st 2010, 7424 blood culture sets were submitted to the Laboratory Department of the Hospital for Clinical Infectious Diseases in Cluj-Napoca, Romania. The blood cultures were performed using BacT/Alert until January 2010 and BacT/Alert 3D automated system (bioMérieux after that date. The blood culture bottles were incubated at 37°C in a continuously monitoring system for up to 7 days. The strain identifications were performed by conventional methods, ApiStaph galleries and Vitek 2 Compact system. Susceptibility to methicillin was determined by disk diffusion method with cefoxitin disk and by using Vitek 2 Compact system. Results: From the total number of performed blood cultures, 568 were positive with Staphylococcus species. From 168 bacteriemic episodes 103 were with Staphylococcus aureus. Among 65 coagulase-negative staphylococci isolates, Staphylococcus epidermidis was the most frequently isolated species (34, followed by Staphylococcus hominis (15, Staphylococcus haemolyticus (8, Staphylococcus saprophyticus (3, Staphylococcus cohnii (1, Staphylococcus auricularis (1, and 3 strains that were not identified at species level. Methicillin resistance was encountered in 53.40% of Staphylococcus aureus strains and in 80% of coagulase-negative staphylococci. Conclusions: An important percentage of blood cultures were contaminated with Staphylococcus species. The main species identified in true bacteriemia cases were Staphylococcus aureus and Staphylococcus epidermidis. The percentage of methicillin-resistance, proved to be high not only for coagulase-negative staphylococci but also for Staphylococcus aureus.

Tigecycline in-vitro susceptibility and antibiotics fitness forgram-negative pathogens

International Nuclear Information System (INIS)

Arya, Subhash C.; Agarwal, N.

2008-01-01

Objective was to determine the tigecycline in-vitro susceptibility ofnaive gram-negative pathogens from serious infections in Delhi, India. DuringJuly to October 2007 investigations were carried out to determine thetigecycline in vitro susceptibility of 50 consecutive gram-negative pathogensfrom serious infections at the Sant Parmanand Hospital, Delhi, India. Minimumtigecycline inhibitory concentrations were determined employing the E testmethod (AB Biodisk). Twenty-four percent of isolates were found to betigecycline resistant or partly susceptible. Susceptibility of the isolateswere lower than meropenem but similar to piperacillin-tazobactum,amoxicillin-clavulanic acid and amikacin. Tigecycline resistance wasprevalent in the gram-negative isolates from serious infections prior to itsmarketing in India. The choice of any recently marketed antibiotic for apilot treatment against serious gram-negative infections should not beautomatic. In the initial phase of its marketing, it should be evaluated inparallel with the antibiotics with excellent local susceptibility profiles.(author)

Fighting infections due to multidrug-resistant Gram-positive pathogens.

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Cornaglia, G

2009-03-01

Growing bacterial resistance in Gram-positive pathogens means that what were once effective and inexpensive treatments for infections caused by these bacteria are now being seriously questioned, including penicillin and macrolides for use against pneumococcal infections and-in hospitals-oxacillin for use against staphylococcal infections. As a whole, multidrug-resistant (MDR) Gram-positive pathogens are rapidly becoming an urgent and sometimes unmanageable clinical problem. Nevertheless, and despite decades of research into the effects of antibiotics, the actual risk posed to human health by antibiotic resistance has been poorly defined; the lack of reliable data concerning the outcomes resulting from antimicrobial resistance stems, in part, from problems with study designs and the methods used in resistence determination. Surprisingly little is known, too, about the actual effectiveness of the many types of intervention aimed at controlling antibiotic resistance. New antibiotics active against MDR Gram-positive pathogens have been recently introduced into clinical practice, and the antibiotic pipeline contains additional compounds at an advanced stage of development, including new glycopeptides, new anti-methicillin-resistant Staphylococcus aureus (MRSA) beta-lactams, and new diaminopyrimidines. Many novel antimicrobial agents are likely to be niche products, endowed with narrow antibacterial spectra and/or targeted at specific clinical problems. Therefore, an important educational goal will be to change the current, long-lasting attitudes of both physicians and customers towards broad-spectrum and multipurpose compounds. Scientific societies, such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), must play a leading role in this process.

Central line-associated bloodstream infections and catheter dwell-time: A theoretical foundation for a rule of thumb.

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Voets, Philip J G M

2018-05-14

Many clinicians know from experience and medical epidemiological literature that the risk of central line-associated bloodstream infections (CLABSI) increases rapidly with a prolonged catheter dwell-time, but how this infection risk increases over time remains obscure. In this manuscript, a clinically useful rule of thumb is derived, stating that the risk of CLABSI increases in a quadratic fashion with the increase in catheter dwell-time. The proposed rule of thumb could be considered a quick and effortless clinical tool to rationally predict the pattern of CLABSI risk with an increasing catheter dwell-time. Copyright © 2018. Published by Elsevier Ltd.

Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume Cardiac Surgical Intensive Care Unit

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Manoj Kumar Sahu

2016-01-01

Full Text Available Background: Nosocomial infections (NIs in the postoperative period not only increase morbidity and mortality, but also impose a significant economic burden on the health care infrastructure. This retrospective study was undertaken to (a evaluate the incidence, characteristics, risk factors and outcomes of NIs and (b identify common microorganisms responsible for infection and their antibiotic resistance profile in our Cardiac Surgical Intensive Care Unit (CSICU. Patients and Methods: After ethics committee approval, the CSICU records of all patients who underwent cardiovascular surgery between January 2013 and December 2014 were reviewed retrospectively. The incidence of NI, distribution of NI sites, types of microorganisms and their antibiotic resistance, length of CSICU stay, and patient-outcome were determined. Results: Three hundred and nineteen of 6864 patients (4.6% developed NI after cardiac surgery. Lower respiratory tract infections (LRTIs accounted for most of the infections (44.2% followed by surgical-site infection (SSI, 11.6%, bloodstream infection (BSI, 7.5%, urinary tract infection (UTI, 6.9% and infections from combined sources (29.8%. Acinetobacter, Klebsiella, Escherichia coli, and Staphylococcus were the most frequent pathogens isolated in patients with LRTI, BSI, UTI, and SSI, respectively. The Gram-negative bacteria isolated from different sources were found to be highly resistant to commonly used antibiotics. Conclusion: The incidence of NI and sepsis-related mortality, in our CSICU, was 4.6% and 1.9%, respectively. Lower respiratory tract was the most common site of infection and Gram-negative bacilli, the most common pathogens after cardiac surgery. Antibiotic resistance was maximum with Acinetobacter spp.

Optimization of linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis.

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Yang, Minjie; Zhang, Jing; Chen, Yuancheng; Liang, Xiaoyu; Guo, Yan; Yu, Jicheng; Zhu, Demei; Zhang, Yingyuan

2017-01-01

To optimize linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis. The minimum inhibitory concentration (MIC) distribution of 572 Gram-positive strains from patients with clinically confirmed infections was analyzed. Using the Monte Carlo simulation method, the cumulative fraction of response and probability of target attainment were determined for linezolid regimens of 600 mg q.12h and q.8h Results: Linezolid dosage of 600 mg q.12h yielded >90% cumulative fraction of response and probability of target attainment for staphylococcal infections with an MIC of ≤1 mg/l, enterococcal infections with higher MIC values required 600 mg q.8h. Linezolid 600 mg q.12h is still the clinically recommended empirical dosage for Gram-positive bacterial infections. However, as bacterial MICs increase, 600 mg q.8h may be required to achieve better efficacy.

ClubSub-P: Cluster-Based Subcellular Localization Prediction for Gram-Negative Bacteria and Archaea

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Paramasivam, Nagarajan; Linke, Dirk

2011-01-01

The subcellular localization (SCL) of proteins provides important clues to their function in a cell. In our efforts to predict useful vaccine targets against Gram-negative bacteria, we noticed that misannotated start codons frequently lead to wrongly assigned SCLs. This and other problems in SCL prediction, such as the relatively high false-positive and false-negative rates of some tools, can be avoided by applying multiple prediction tools to groups of homologous proteins. Here we present ClubSub-P, an online database that combines existing SCL prediction tools into a consensus pipeline from more than 600 proteomes of fully sequenced microorganisms. On top of the consensus prediction at the level of single sequences, the tool uses clusters of homologous proteins from Gram-negative bacteria and from Archaea to eliminate false-positive and false-negative predictions. ClubSub-P can assign the SCL of proteins from Gram-negative bacteria and Archaea with high precision. The database is searchable, and can easily be expanded using either new bacterial genomes or new prediction tools as they become available. This will further improve the performance of the SCL prediction, as well as the detection of misannotated start codons and other annotation errors. ClubSub-P is available online at http://toolkit.tuebingen.mpg.de/clubsubp/ PMID:22073040

Protein secretion and membrane insertion systems in gram-negative bacteria.

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Saier, Milton H

2006-01-01

In contrast to other organisms, gram-negative bacteria have evolved numerous systems for protein export. Eight types are known that mediate export across or insertion into the cytoplasmic membrane, while eight specifically mediate export across or insertion into the outer membrane. Three of the former secretory pathway (SP) systems, type I SP (ISP, ABC), IIISP (Fla/Path) and IVSP (Conj/Vir), can export proteins across both membranes in a single energy-coupled step. A fourth generalized mechanism for exporting proteins across the two-membrane envelope in two distinct steps (which we here refer to as type II secretory pathways [IISP]) utilizes either the general secretory pathway (GSP or Sec) or the twin-arginine targeting translocase for translocation across the inner membrane, and either the main terminal branch or one of several protein-specific export systems for translocation across the outer membrane. We here survey the various well-characterized protein translocation systems found in living organisms and then focus on the systems present in gram-negative bacteria. Comparisons between these systems suggest specific biogenic, mechanistic and evolutionary similarities as well as major differences.

VIP as a potential therapeutic agent in gram negative sepsis.

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Ibrahim, Hiba; Barrow, Paul; Foster, Neil

2012-12-01

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Clinical pulmonary infection score and a spot serum procalcitonin level to guide discontinuation of antibiotics in ventilator-associated pneumonia: a study in a single institution with high prevalence of nonfermentative gram-negative bacilli infection.

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Wongsurakiat, Phunsup; Tulatamakit, Sirapat

2018-01-01

Background We wanted to determine the impact of combined Clinical Pulmonary Infection Score (CPIS) and a spot serum procalcitonin (PCT)-guided protocol to shorten the duration of antibiotic treatment in patients with ventilator-associated pneumonia (VAP), mainly caused by nonfermentative gram-negative bacilli (NF-GNB). Methods Patients with VAP who received appropriate antibiotics for 7 days, temperature ⩽ 37.8°C, without shock, and CPIS ⩽ 6 were allocated to the PCT group or conventional group according to the treating physicians' decisions. In the PCT group, antibiotics were stopped if the PCT level on day 8 level appeared effective and safe to guide discontinuation of antibiotic treatment in patients with VAP caused by NF-GNB. TCTR20160726002.

Is Clostridium difficile infection a risk factor for subsequent bloodstream infection?

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Ulrich, Robert J; Santhosh, Kavitha; Mogle, Jill A; Young, Vincent B; Rao, Krishna

2017-12-01

Clostridium difficile infection (CDI) is a common nosocomial diarrheal illness increasingly associated with mortality in United States. The underlying factors and mechanisms behind the recent increases in morbidity from CDI have not been fully elucidated. Murine models suggest a mucosal barrier breakdown leads to bacterial translocation and subsequent bloodstream infection (BSI). This study tests the hypothesis that CDI is associated with subsequent BSI in humans. We conducted a retrospective cohort study on 1132 inpatients hospitalized >72 h with available stool test results for toxigenic C. difficile. The primary outcome was BSI following CDI. Secondary outcomes included 30-day mortality, colectomy, readmission, and ICU admission. Unadjusted and adjusted logistic regression models were developed. CDI occurred in 570 of 1132 patients (50.4%). BSI occurred in 86 (7.6%) patients. Enterococcus (14%) and Klebsiella (14%) species were the most common organisms. Patients with BSI had higher comorbidity scores and were more likely to be male, on immunosuppression, critically ill, and have a central venous catheter in place. Of the patients with BSI, 36 (42%) had CDI. CDI was not associated with subsequent BSI (OR 0.69; 95% CI 0.44-1.08; P = 0.103) in unadjusted analysis. In multivariable modeling, CDI appeared protective against subsequent BSI (OR 0.57; 95% CI 0.34-0.96; P = 0.036). Interaction modeling suggests a complicated relationship among CDI, BSI, antibiotic exposure, and central venous catheter use. In this cohort of inpatients that underwent testing for CDI, CDI was not a risk factor for developing subsequent BSI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Emergence in Taiwan of novel imipenem-resistant Acinetobacter baumannii ST455 causing bloodstream infection in critical patients.

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Lee, Hao-Yuan; Huang, Chih-Wei; Chen, Chyi-Liang; Wang, Yi-Hsin; Chang, Chee-Jen; Chiu, Cheng-Hsun

2015-12-01

Acinetobacter baumannii is one of the most important nosocomial pathogens worldwide. This study aimed to use multilocus sequence typing (MLST) for the epidemiological surveillance of A. baumannii isolates in Taiwan and analyze the clinical presentations and patients' outcome. MLST according to both Bartual's PubMLST and Pasteur's MLST schemes was applied to characterize bloodstream imipenem-resistant A. baumannii (IRAB) infection in intensive care units in a medical center. A total of 39 clinical IRAB bloodstream isolates in 2010 were enrolled. We also collected 13 imipenem-susceptible A. baumannii (ISAB) bloodstream isolates and 30 clinical sputum isolates (24 IRAB and 6 ISAB) for comparison. Clinical presentations and outcome of the patients were analyzed. We found that infection by ST455(B)/ST2(P) and inappropriate initial therapy were statistically significant risk factors for mortality. More than one-third of the IRAB isolates belonged to ST455(B)/ST2(P). Most ST455(B)/ST2(P) (80%) carried ISAba1-blaOXA-23, including 10 (66.7%) with Tn2006 (ISAba1-blaOXA-23-ISAba1) in an AbaR4-type resistance island. ST455(B)/ST2(P) appears to evolve from ST208(B)/ST2(P) of clonal complex (CC) 92(B)/CC2(P). In this hospital-based study, A. baumannii ST455 accounted for 38.5% of IRAB bacteremia, with a high mortality of 86.7%. Approximately 85% of ST455(B)/ST2(P)bacteremia had a primary source of ventilation-associated pneumonia. We report the emergence in Taiwan of IRAB ST455(B)/ST2(P), which is the current predominant clone of IRAB in our hospital and has been causing bacteremia with high mortality in critical patients. Copyright © 2015. Published by Elsevier B.V.

Detection of extra-cellular enzymes of anaerobic gram-negative bacteria from clinically diseased and healthy sites

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Nagmoti J

2008-01-01

Full Text Available Anaerobic gram-negative bacteria (AGNB produce enzymes that play a significant role in the development of disease. We tested 50 AGNB isolates, 25 each from clinically diseased and healthy human sites for in vitro production of caseinase, collagenase, etc. Majority of the isolates were Bacteroides fragilis and Porphyromonas gingivalis, which more commonly produced collagenase and haemolysin. Comparatively larger number of clinical AGNB produced collagenase (P = 0.004. No such difference was observed with other enzymes. Hence, collagenase is probably one of the key virulence markers of pathogenic AGNB, and the inhibitors targeting collagenases might help in the therapy of anaerobic infections.

Beyond the bundle: a survey of central line-associated bloodstream infection prevention practices used in US and Canadian pediatric hospitals.

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Klieger, Sarah B; Potter-Bynoe, Gail; Quach, Caroline; Sandora, Thomas J; Coffin, Susan E

2013-11-01

We surveyed US and Canadian pediatric hospitals about their use of central line-associated bloodstream infection (CLABSI) prevention strategies beyond typical insertion and maintenance bundles. We found wide variation in supplemental strategies across hospitals and in their penetration within hospitals. Future studies should assess specific adjunctive prevention strategies and CLABSI rates.

Risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country

International Nuclear Information System (INIS)

Kalam, K.; Kumar, S.; Ali, S.; Baqi, S.; Qamar, F.

2014-01-01

Objective: To identify the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia in a developing country. Methods: A prospective cohort study was conducted at the Sindh Institute of Urology and Transplantation (SIUT) from June to October 2012. Hospitalized patients > 15 years of age with gram negative bacteraemia were included and followed for a period of 2 weeks for in hospital mortality. Data was collected and analyzed for 243 subjects. Multivariate analysis was used to determine the risk factors for carbapenem resistant bacteraemia and mortality due to gram negative bacteraemia. Crude and adjusted odds ratio and 95% CI are reported. Results: A total of 729 out of 1535 (47.5%) cultures were positive for gram negative isolates. Out of 243 subjects, 117 (48%) had an MDR isolate. Having an MDR isolate on culture (AOR, 2.33; 95% CI, 1.35 -4.0), having multiple positive cultures (AOR, 1.8; 95% CI, 0.94 -3.4) and stay in ICU >48 hours (AOR, 2.0 ; 95% CI, 1.12 -3.78) were identified as significant risk factors for mortality due to gram negative organisms. Risk factors for carbapenem resistant bacteraemia were age >50 years (AOR, 1.83; 95% CI, 1.0-3.5), septic shock on presentation (AOR 2.53; 95% CI, 1.03 -6.2) , ICU stay of >72 hours (AOR 2.40; 95% CI, 1.14-5.0) and receiving immunosuppressant medications (AOR 2.23; 95% CI, 0.74 - 6.7). Conclusion: There is a high burden of MDR and carbapenem resistant gram negative bacteraemia, with a high mortality rate. (author)

Subcellular localization for Gram positive and Gram negative bacterial proteins using linear interpolation smoothing model.

Science.gov (United States)

Saini, Harsh; Raicar, Gaurav; Dehzangi, Abdollah; Lal, Sunil; Sharma, Alok

2015-12-07

Protein subcellular localization is an important topic in proteomics since it is related to a protein׳s overall function, helps in the understanding of metabolic pathways, and in drug design and discovery. In this paper, a basic approximation technique from natural language processing called the linear interpolation smoothing model is applied for predicting protein subcellular localizations. The proposed approach extracts features from syntactical information in protein sequences to build probabilistic profiles using dependency models, which are used in linear interpolation to determine how likely is a sequence to belong to a particular subcellular location. This technique builds a statistical model based on maximum likelihood. It is able to deal effectively with high dimensionality that hinders other traditional classifiers such as Support Vector Machines or k-Nearest Neighbours without sacrificing performance. This approach has been evaluated by predicting subcellular localizations of Gram positive and Gram negative bacterial proteins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differences in microbiological profile between community-acquired, healthcare-associated and hospital-acquired infections.

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Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Sarmento, António

2013-01-01

Microbiological profiles were analysed and compared for intra-abdominal, urinary, respiratory and bloodstream infections according to place of acquisition: community-acquired, with a separate analysis of healthcare-associated, and hospital-acquired. Prospective cohort study performed at a university tertiary care hospital over 1 year. Inclusion criteria were meeting the Centers for Disease Control definition of intra-abdominal, urinary, respiratory and bloodstream infections. A total of 1035 patients were included in the study. More than 25% of intra-abdominal infections were polymicrobial; multi-drug resistant gram-negatives were 38% in community-acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was the most prevalent among urinary infections: 69% in community-acquired, 56% in healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens were 10% in healthcare-associated and 3% in community-acquired and hospital-acquired. In respiratory infections Streptococcus pneumoniae was the most prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and hospital-acquired (24%). A significant association was found between MRSA respiratory infection and hospitalization in the previous year (adjusted OR = 6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic therapy (adjusted OR = 5.7); no cases were documented among patients without risk factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare-associated and 19% in hospital-acquired infection. This study shows that healthcare-associated has a different microbiologic profile than those from community or hospital acquired for the four main focus of infection. Knowledge of this fact is important because the existing guidelines for community-acquired are not entirely applicable for this group of patients.

Detection of AmpC β lactamases in gram-negative bacteria

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Gunjan Gupta

2014-01-01

Full Text Available Amp C β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor/β-lactam combinations. The increase in antibiotic resistance among Gram-negative bacteria is a notable example of how bacteria can procure, maintain and express new genetic information that can confer resistance to one or several antibiotics. Detection of organisms producing these enzymes can be difficult, because their presence does not always produce a resistant phenotype on conventional disc diffusion or automated susceptibility testing methods. These enzymes are often associated with potentially fatal laboratory reports of false susceptibility to β-lactams phenotypically. With the world-wide increase in the occurrence, types and rate of dissemination of these enzymes, their early detection is critical. AmpC β-lactamases show tremendous variation in geographic distribution. Thus, their accurate detection and characterization are important from epidemiological, clinical, laboratory, and infection control point of view. This document describes the methods for detection for AmpC β-lactamases, which can be adopted by routine diagnostic laboratories.

Antimicrobial-resistant infections among postpartum women at a Ugandan referral hospital.

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Lisa M Bebell

Full Text Available Puerperal sepsis causes 10% of maternal deaths in Africa, but prospective studies on incidence, microbiology and antimicrobial resistance are lacking.We performed a prospective cohort study of 4,231 Ugandan women presenting to a regional referral hospital for delivery or postpartum care, measured vital signs after delivery, performed structured physical exam, symptom questionnaire, and microbiologic evaluation of febrile and hypothermic women. Malaria rapid diagnostic testing, blood and urine cultures were performed aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial susceptibility and breakpoints were determined using disk diffusion per EUCAST standards. Hospital diagnoses, treatments and outcomes were abstracted from patient charts.Mean age was 25 years, 12% were HIV-infected, and 50% had cesarean deliveries. Approximately 5% (205/4176 with ≥1 temperature measurement recorded developed postpartum fever or hypothermia; blood and urine samples were collected from 174 (85%, and 17 others were evaluated clinically. Eighty-four (48% had at least one confirmed source of infection: 39% (76/193 clinical postpartum endometritis, 14% (25/174 urinary tract infection (UTI, 3% (5/174 bloodstream infection. Another 3% (5/174 had malaria. Overall, 30/174 (17% had positive blood or urine cultures, and Acinetobacter species were the most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80% were multidrug-resistant and cefepime non-susceptible.For women in rural Uganda with postpartum fever, we found a high rate of antibiotic resistance among cultured urinary and bloodstream infections, including cephalosporin-resistant Acinetobacter species. Increasing availability of microbiology testing to inform appropriate antibiotic use, development of antimicrobial stewardship programs, and strengthening infection control practices should be high priorities.

Clinical update on linezolid in the treatment of Gram-positive bacterial infections

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Ager, Sally; Gould, Kate

2012-01-01

Gram-positive pathogens are a significant cause of morbidity and mortality in both community and health care settings. Glycopeptides have traditionally been the antibiotics of choice for multiresistant Gram-positive pathogens but there are problems with their use, including the emergence of glycopeptide-resistant strains, tissue penetration, and achieving and monitoring adequate serum levels. Newer antibiotics such as linezolid, a synthetic oxazolidinone, are available for the treatment of resistant Gram-positive bacteria. Linezolid is active against a wide range of Gram-positive bacteria and has been generally available for the treatment of Gram-positive infections since 2000. There are potential problems with linezolid use, including its bacteriostatic action and the relatively high incidence of reported adverse effects, particularly with long-term use. Long-term use may also be complicated by the development of resistance. However, linezolid has been shown to be clinically useful in the treatment of several serious infections where traditionally bacteriocidal agents have been required and many of its adverse effects are reversible on cessation. It has also been shown to be a cost-effective treatment option in several studies, with its high oral bioavailability allowing an early change from intravenous to oral formulations with consequent earlier patient discharge and lower inpatient costs. PMID:22787406

The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

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Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

2014-01-01

♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334

Long-term survival and function after suspected gram-negative sepsis.

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Perl, T M; Dvorak, L; Hwang, T; Wenzel, R P

1995-07-26

To determine the long-term (> 3 months) survival of septic patients, to develop mathematical models that predict patients likely to survive long-term, and to measure the health and functional status of surviving patients. A large tertiary care university hospital and an associated Veterans Affairs Medical Center. From December 1986 to December 1990, a total of 103 patients with suspected gram-negative sepsis entered a double-blind, placebo-controlled efficacy trial of monoclonal antiendotoxin antibody. Of these, we followed up 100 patients for 7667 patient-months. Beginning in May 1992, we reviewed hospital records and contacted all known survivors. We measured the health status of all surviving patients. The determinants of long-term survival (up to 6 years) were identified through two Cox proportional hazard regression models: one that included patient characteristics identified at the time of sepsis (bedside model) and another that included bedside, infection-related, and treatment characteristics (overall model). Of the 60 patients in the cohort who died at a median interval of 30.5 days after sepsis, 32 died within the first month of the septic episode, seven died within 3 months, and four more died within 6 months. In the bedside multivariate model constructed to predict long-term survival, large hazard ratios (HRs) were associated with severity of underlying illness as classified by McCabe and Jackson criteria (for rapidly fatal disease, HR = 30.4, P respiratory distress syndrome (HR = 2.3; P = .02) predicted patients most likely to die. The Acute Physiology and Chronic Health Evaluation II score was not a significant predictor of outcome when either model included the simpler McCabe and Jackson classification of underlying disease severity. We compared the health status scores with norms for the general population and found that patients with resolved sepsis reported more physical dysfunction (P bedridden), suggesting that the patients' physical function

Identification and Whole Genome Sequencing of the First Case of Kosakonia radicincitans Causing a Human Bloodstream Infection

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Bhatti, Micah D.; Kalia, Awdhesh; Sahasrabhojane, Pranoti; Kim, Jiwoong; Greenberg, David E.; Shelburne, Samuel A.

2017-01-01

The taxonomy of Enterobacter species is rapidly changing. Herein we report a bloodstream infection isolate originally identified as Enterobacter cloacae by Vitek2 methodology that we found to be Kosakonia radicincitans using genetic means. Comparative whole genome sequencing of our isolate and other published Kosakonia genomes revealed these organisms lack the AmpC β-lactamase present on the chromosome of Enterobacter sp. A fimbriae operon primarily found in Escherichia coli O157:H7 isolates ...

Antimicrobial resistance pattern of Gram –negative bacilli isolated of Vali-Asr Hospital wards in Arak

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Farshid Didgar

2014-11-01

Full Text Available Background: Infectious diseases are of the most important causes of mortality all around the world particular in developing countries. Recently, the most important thing that has worried medical society is antibiotic resistance. Multi-resistant gram_negative rods are important pathogens in hospitals, causing high rate of mortality.The main goal of this study was to investigate the antimicrobial resistance patterns among common gram-negative bacilli isolated from patients of Vali-Asr Hospital. Material and Methods: This is a cross-sectional descriptive study conducted between the years 2010-2012 in Vali-Asr hospital in Arak. In this study 1120 specimen were examined. Bacterial strains were isolated by conventional methods from various clinical samples of patients including: blood, urine, wound, sputum, CSF, andetc.All isolates were examined for antimicrobial resistance using disc diffusion method. Results: In this study 737 specimen were positive cultures. A total of 332 isolates of Gram-negative bacilli were identified. The most frequent gram negative bacteria were isolated from urine, wound, blood, respiratory secretion and catheter. The most frequent pathogens were E.coli followed by k.pneumonia, entrobacter, p.oaeruginosa, Acinetobacter spp, citrobacter and proteus. High rate of resistance to third generation of cephalospoins & carbapenems observed amang isolates of Acintobacter spp.Prodution of extended spectrum beralactamases (ESBLS was found in 51.4% of all Gram negative bacteria. Conclusion: Antibiotic resistance, particularly multi-drug resistance is frequent among microorganisms of ValiAsr Hospital. Resistance in our country, like other countries have been shown to be increased, so it is highly recommended to prohibit unnecessary prescription of antibiotics.

Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review.

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Warhurst, Geoffrey; Dunn, Graham; Chadwick, Paul; Blackwood, Bronagh; McAuley, Daniel; Perkins, Gavin D; McMullan, Ronan; Gates, Simon; Bentley, Andrew; Young, Duncan; Carlson, Gordon L; Dark, Paul

2015-05-01

antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy. SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is

ClubSub-P: Cluster-based subcellular localization prediction for Gram-negative bacteria and Archaea.

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Nagarajan eParamasivam

2011-11-01

Full Text Available The subcellular localization of proteins provides important clues to their function in a cell. In our efforts to predict useful vaccine targets against Gram-negative bacteria, we noticed that misannotated start codons frequently lead to wrongly assigned subcellular localizations. This and other problems in subcellular localization prediction, such as the relatively high false positive and false negative rates of some tools, can be avoided by applying multiple prediction tools to groups of homologous proteins. Here we present ClubSub-P, an online database that combines existing subcellular localization prediction tools into a consensus pipeline from more than 600 proteomes of fully sequenced microorganisms. On top of the consensus prediction at the level of single sequences, the tool uses clusters of homologous proteins from Gram-negative bacteria and from Archaea to eliminate false positive and false negative predictions. ClubSub-P can assign the subcellular localization of proteins from Gram-negative bacteria and Archaea with high precision. The database is searchable, and can easily be expanded using either new bacterial genomes or new prediction tools as they become available. This will further improve the performance of the subcellular localization prediction, as well as the detection of misannotated start codons and other annotation errors. ClubSub-P is available online at http://toolkit.tuebingen.mpg.de/clubsubp/

Distribution of Gram Negative Bacteria and Evaluation of Resistance Profiles

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Serap Pamukcuoglu

2014-03-01

Full Text Available Aim: In this study, we aimed to examine the distributon of Gram negative bacteria isolated from urine cultures of out-patients in Afyonkarahisar State Hospital and evaluate the antimicrobial resistance rates of these pathogens. Material and Method: Urine samples of out-patients which were sent to microbiology laboratory between 2012-2013 were retrospectively evaluated. The isolates were identified using conventional methods and/or automated Vitec 2.0 system. Antibiogram sensitivities were determined by Kirby-Bauer disc diffusion method or automated system and interpreted on the basis of Clinical and Laboratory Standards Institute (CSI criteria. Double disc sinergy test (DDST or Vitec 2.0 system was used to detect extended spectrum beta-lactamase (ESBL.When conventional methods could%u2019t be clarified according to their colony morphologies, gram staining patterns, biochemical test; automated system has been used. Results: A total of 671 isolates acquired from urine samples were studied. 427 Escherichia coli (63.6 %, 165 Klebsiella spp. (24.6 %, 22 Pseudomonas spp. (3.3 %, nine Acinetobacter spp. (1.3 %, 41 Proteus spp. (6.1 % and seven Serratia (1.0 % strains were identified among isolates. 97 E.coli (22.8 % and 41 Klebsiella (24.8 % isolates were ESBL positive. Most common bacteria were E.coli, 31.1 % of which were resistant to trimethoprim-sulfamethoxazole, 16 % to ciprofloxacin and 3.6 % to nitrofurantoin. Among Enterobacteriaceae, no resistance aganist carbapenems were detected. Moreover, aminoglicoside sensitivity rate was significantly high in this group. Discussion: Microorganisms that have progressively increasing antimicrobial resistance should be considered in the treatment of urinary tract infections. It is also important to use the most appropriate antibiotics to avoid unnecessary usage of these drugs in order to decrease drug resistance rates and ESBL production which may effect the success of the treatment.

In Vitro Analysis of Pseudomonas aeruginosa Virulence Using Conditions That Mimic the Environment at Specific Infection Sites.

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Colmer-Hamood, J A; Dzvova, N; Kruczek, C; Hamood, A N

2016-01-01

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes chronic lung infection in patients with cystic fibrosis (CF) and acute systemic infections in severely burned patients and immunocompromised patients including cancer patients undergoing chemotherapy and HIV infected individuals. In response to the environmental conditions at specific infection sites, P. aeruginosa expresses certain sets of cell-associated and extracellular virulence factors that produce tissue damage. Analyzing the mechanisms that govern the production of these virulence factors in vitro requires media that closely mimic the environmental conditions within the infection sites. In this chapter, we review studies based on media that closely resemble three in vivo conditions, the thick mucus accumulated within the lung alveoli of CF patients, the serum-rich wound bed and the bloodstream. Media resembling the CF alveolar mucus include standard laboratory media supplemented with sputum obtained from CF patients as well as prepared synthetic mucus media formulated to contain the individual components of CF sputum. Media supplemented with serum or individual serum components have served as surrogates for the soluble host components of wound infections, while whole blood has been used to investigate the adaptation of pathogens to the bloodstream. Studies using these media have provided valuable information regarding P. aeruginosa gene expression in different host environments as varying sets of genes were differentially regulated during growth in each medium. The unique effects observed indicate the essential role of these in vitro media that closely mimic the in vivo conditions in providing accurate information regarding the pathogenesis of P. aeruginosa infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.

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Nachimuthu, Ramesh; Subramani, Ramkumar; Maray, Suresh; Gothandam, K M; Sivamangala, Karthikeyan; Manohar, Prasanth; Bozdogan, Bülent

2016-10-01

Carbapenem resistance is disseminating worldwide among Gram-negative bacteria. The aim of this study was to identify carbapenem-resistance level and to determine the mechanism of carbapenem resistance among clinical isolates from two centres in Tamil Nadu. In the present study, a total of 93 Gram-negative isolates, which is found to be resistant to carbapenem by disk diffusion test in two centres, were included. All isolates are identified at species level by 16S rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM, blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected carbapenem-resistant isolates, 27 had meropenem MICs ≥ 2 μg/ml. The MIC range, MIC50 and MIC90 were 128 μg/ml, 0.12 and 16 μg/ml, respectively. Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48, 22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%), Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli, four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K. pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A total of seven carbapenem-resistant isolates were negatives by PCR for the genes studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2 μg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181 beta-lactamase among Gram-negative bacteria in South India. This study showed the emergence of NDM producer in clinical isolates of E

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease.

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Gopal, Vani; Mangaiyarkarasi, T; Gopal, R

2014-01-01

Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen's disease. A middle-aged man with a known case of diabetes mellitus and Hansen's disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Patient was operated for cataract and Intraocular lens implanted. Patient developed headache and vomiting on the 4th post-operative day. Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram-negative bacilli in the direct smear and culture yielded a heavy growth of K. pneumoniae. The patient was treated with antimicrobials according to the susceptibility pattern. He initially showed improvement but later on developed altered sensorium and hypotension. Patient succumbed to infection in spite of all medical attention.

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease

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Vani Gopal

2014-01-01

Full Text Available Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease. A middle-aged man with a known case of diabetes mellitus and Hansen′s disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Patient was operated for cataract and Intraocular lens implanted. Patient developed headache and vomiting on the 4 th post-operative day. Lumbar puncture was carried out and gram stain of cerebrospinal fluid showed Gram-negative bacilli in the direct smear and culture yielded a heavy growth of K. pneumoniae. The patient was treated with antimicrobials according to the susceptibility pattern. He initially showed improvement but later on developed altered sensorium and hypotension. Patient succumbed to infection in spite of all medical attention.

Comparison of the Cathra Repliscan II, the AutoMicrobic system Gram-Negative General Susceptibility-Plus Card, and the Micro-Media System Fox Panel for dilution susceptibility testing of gram-negative bacilli.

Science.gov (United States)

Reiber, N E; Kelly, M T; Latimer, J M; Tison, D L; Hysmith, R M

1985-06-01

A comparative evaluation was done to test the accuracy of the Cathra Repliscan II agar dilution system (Diagnostic Equipment, Inc., St. Paul, Minn.), the AutoMicrobic system with Gram-Negative General Susceptibility-Plus Card (Vitek Systems, Inc., Hazelwood, Mo.), and the Micro-Media Fox Panel micro broth dilution system (Micro-Media Systems, Inc., San Jose, Calif.) in determining MICs of 12 antibiotics for 200 gram-negative bacilli. Of the 200 strains tested, 12 isolates did not grow in one of the three systems. The 188 remaining organisms included 158 members of the family Enterobacteriaceae, 20 Pseudomonas spp., 5 Acinetobacter sp., 3 Aeromonas spp., and 2 Vibrio spp. A total of 2,256 organism-antibiotic combinations were analyzed for each system. An MIC was considered correct if two of the three systems were in agreement. When disagreements occurred, correct MICs were determined by the standard agar dilution method. With this criterion, overall agreements of the Cathra Repliscan II system, AutoMicrobic system, and Micro-Media Fox Panel system were 94.7, 94.9, and 95.5%, respectively. Tetracycline (20%), nitrofurantoin (20%), and ampicillin (16%) accounted for 56% of the discrepancies observed. These results indicate that all three systems perform with a high degree of accuracy for susceptibility testing of gram-negative bacilli.

Trojan Horse Antibiotics-A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

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Tillotson, Glenn S

2016-01-01

Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed.

Gram-negative bacteria account for main differences between faecal microbiota from patients with ulcerative colitis and healthy controls

DEFF Research Database (Denmark)

Vigsnæs, Louise Kristine; Brynskov, J.; Steenholdt, C.

2012-01-01

process of the gut mucosa. The aim of this study was to investigate the faecal microbiota in patients either with UC in remission (n=6) or with active disease (n=6), and in healthy controls (n=6). The composition of Gram-negative bacteria and Gram-positive bacteria was examined. Antigenic structures...... of Gram-negative bacteria such as lipopolysaccharides have been related to the inflammatory responses and pathogenesis of inflammatory bowel disease. Dice cluster analysis and principal component analysis of faecal microbiota profiles obtained by denaturing gradient gel electrophoresis and quantitative...... PCR, respectively, revealed that the composition of faecal bacteria from UC patients with active disease differed from the healthy controls and that this difference should be ascribed to Gram-negative bacteria. The analysis did not show any clear grouping of UC patients in remission. Even...

DMPD: Gram-negative endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 1916089 Gram-negative endotoxin: an extraordinary lipid with profound effects oneuk...ep;5(12):2652-60. (.png) (.svg) (.html) (.csml) Show Gram-negative endotoxin: an extraordinary lipid with profound effects...tive endotoxin: an extraordinary lipid with profound effects oneukaryotic signal transduction. Authors Raetz

16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reaction in the Diagnosis of Bloodstream Infections: A Systematic Review and Meta-Analysis.

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Su, Guoming; Fu, Zhuqing; Hu, Liren; Wang, Yueying; Zhao, Zuguo; Yang, Weiqing

2015-01-01

We aim to evaluate the accuracy of the 16S ribosomal ribonucleic acid (rRNA) gene polymerase chain reaction (PCR) test in the diagnosis of bloodstream infections through a systematic review and meta-analysis. A computerized literature search was conducted to identify studies that assessed the diagnostic value of 16S rRNA gene PCR test for bloodstream infections. Study quality was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence intervals (95% CI) for each study. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Statistical analysis was performed in Meta-DiSc 1.4 and Stata/SE 12.0 software. Twenty-eight studies were included in our meta-analysis. Using random-effect model analysis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.87 (95% CI, 0.85-0.89), 0.94 (95% CI, 0.93-0.95), 12.65 (95% CI, 8.04-19.90), 0.14 (95% CI, 0.08-0.24), and 116.76 (95% CI, 52.02-262.05), respectively. The SROC curve indicated that the area under the curve (AUC) was 0.9690 and the maximum joint sensitivity and specificity (Q*) was 0.9183. In addition, heterogeneity was statistically significant but was not caused by the threshold effect. Existing data suggest that 16S rRNA gene PCR test is a practical tool for the rapid screening of sepsis. Further prospective studies are needed to assess the diagnostic value of PCR amplification and DNA microarray hybridization of 16S rRNA gene in the future.

[Development and Evaluation of a New Selective Culture Medium, KBM Anaero RS-GNR, for Detection of Anaerobic Gram Negative Rods].

Science.gov (United States)

Narita, Taeko; Kato, Kyohei; Hanaiwa, Hiroki; Harada, Tetsuhiro; Funashima, Yumiko; Akiwa, Makoto; Sekiguchi, Jun-Ichiro; Nagasawa, Zenzo; Umemura, Tsukuru

2017-03-22

The laboratory culture methods for isolating drug-resistant pathogens has been the gold standard in medical microbiology, and play pivotal roles in the overall management of infectious diseases. Recently, several reports have emphasized the development of antibiotics-resistance among anaerobic gram-negative rods, especially Genus Bacteroides and Prevotella . Therefore, a selective culture method to detect these pathogens is needed. We developed here the new selective culture medium, termed "KBM Anaero RS-GNR," for detecting anaerobic Gram-negative rods. Growth capability and selectivity of the agar medium were assessed by using the pure culture suspensions of more than 100 bacterial strains as well as the 13 samples experimentally contaminated with these bacterial strains. This new medium, "KBM Anaero RS-GNR," successfully showed the selective isolation of anaerobic Gram-negative rods. Compared with commercially available medium, "PV Brucella HK Agar, " which is also designed to detect anaerobic Gram-negative rods, there was no significant difference of the overall detection efficiency between two media. However, "KBM Anaero RS-GNR" showed superior to selectivity for anaerobic Gram-negative rods, especially from the samples contaminated with Candida species. Thus, the culture method using KBM Anaero RS-GNR is relevant for isolation of anaerobic Gram-negative rods especially from clinical specimens.

Fatal Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease

OpenAIRE

Vani Gopal; T Mangaiyarkarasi; R Gopal

2014-01-01

Klebsiella is a Gram-negative bacterium that causes different types of health care-associated infections including pneumonia, bloodstream infections, surgical site infections and meningitis. We report here a case of Klebsiella pneumoniae meningitis in a patient with diabetes mellitus and Hansen′s disease. A middle-aged man with a known case of diabetes mellitus and Hansen′s disease presented with the complaints of blurred vision in the left eye and the patient was found to have cataract. Pati...

Recent advances in the microbiological diagnosis of bloodstream infections.

Science.gov (United States)

Florio, Walter; Morici, Paola; Ghelardi, Emilia; Barnini, Simona; Lupetti, Antonella

2018-05-01

Rapid identification (ID) and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections (BSIs) are essential for the prompt administration of an effective antimicrobial therapy, which can result in clinical and financial benefits. Immediately after blood sampling, empirical antimicrobial therapy, chosen on clinical and epidemiological data, is administered. When ID and AST results are available, the clinician decides whether to continue or streamline the antimicrobial therapy, based on the results of the in vitro antimicrobial susceptibility profile of the pathogen. The aim of the present study is to review and discuss the experimental data, advantages, and drawbacks of recently developed technological advances of culture-based and molecular methods for the diagnosis of BSI (including mass spectrometry, magnetic resonance, PCR-based methods, direct inoculation methods, and peptide nucleic acid fluorescence in situ hybridization), the understanding of which could provide new perspectives to improve and fasten the diagnosis and treatment of septic patients. Although blood culture remains the gold standard to diagnose BSIs, newly developed methods can significantly shorten the turnaround time of reliable microbial ID and AST, thus substantially improving the diagnostic yield.

Molecular studies on bacteriophage endolysins and their potential to control gram-negative bacteria

OpenAIRE

Oliveira, Hugo Alexandre Mendes

2014-01-01

Thesis for PhD degree in Chemical and Biological Engineeering Bacteriophages are viruses that specifically infect bacterial hosts to reproduce. At the end of the infection cycle, progeny virions are confronted with a rigid cell wall that impedes their release into the environment. Consequently, bacteriophages encode hydrolytic enzymes, called endolysins, to digest the peptidoglycan and cause bacteriolysis. In contrast to their extensively studied counterparts, active against Gram-positi...

Higher order structure in the 3'-minor domain of small subunit ribosomal RNAs from a gram negative bacterium, a gram positive bacterium and a eukaryote

DEFF Research Database (Denmark)

Douthwaite, S; Christensen, A; Garrett, R A

1983-01-01

of additional higher order structure in the renatured free RNA. It can be concluded that a high level of conservation of higher order structure has occurred during the evolution of the gram negative and gram positive eubacteria and the eukaryote in both the double helical regions and the "unstructured" regions...

Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015

DEFF Research Database (Denmark)

Hasman, H.; Hammerum, A. M.; Hansen, F.

2015-01-01

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...

Bio sorption of some Rare Earth Elements and Yttrium by Gram Positive and Gram Negative Bacteria

International Nuclear Information System (INIS)

Ibrahim, H.A.

2012-01-01

The separate bio sorption of the REEs La, Sm, Eu and Dy together with yttrium upon the Gram positive bacteria Bacillus subtilis (B.subtilis) and Bacillus Licheniformis (B. Licheniformis),the Gram negative bacterium Escherichia coli (E. coli ) and Saccharomyces cervisiae (Yeast) was studied. The revelant factors of ph 1-6, contact time (30-180 min), the initial rare earth concentration (50-200 mg/l) have been studied. The amount of the accumulated element was strongly affected by its concentration.In addition, bio sorptive fractionation of Y and the studied REEs from a solution containing a mixture of these elements was also studied. From the obtained data, it was found that Langmuir isotherm model for both B.licheniformis and E.coli gives a best fit for the studied elements over the working range of concentration (50-200 mg/I). Transmission electron microscopy exhibited accumulation throughout the bacterial cell with some granular deposits in both the cell periphery and cytoplasm

Impact of universal disinfectant cap implementation on central line-associated bloodstream infections.

Science.gov (United States)

Merrill, Katreena Collette; Sumner, Sharon; Linford, Lorraine; Taylor, Carrie; Macintosh, Christopher

2014-12-01

Central line-associated bloodstream infections (CLABSIs) result in increased length of stay, cost, and patient morbidity and mortality. One CLABSI prevention method is disinfection of intravenous access points. The literature suggests that placing disinfectant caps over needleless connectors decreases CLABSI risk. A quasi-experimental intervention study was conducted in a >430-bed trauma I center. In addition to an existing standard central line bundle, a new intervention consisting of a luer-lock disinfectant cap with 70% alcohol was implemented in all intravenous (IV) needleless connectors on patients with peripheral and central lines. Compliance to the disinfectant cap was monitored weekly. A generalized linear model using a Poisson distribution was fit to determine if there were significant relationships between CLABSIs and disinfectant cap use. Impacts on costs were also examined. The rate of CLABSI decreased following implementation of the disinfectant cap. The incidence rate ratios (.577, P = .004) for implementing the disinfectant caps was statistically significant, indicating that the rate of patient infections decreased by >40%. Increased compliance rates were associated with lower infection rates. Disinfectant cap use was associated with an estimated savings of almost $300,000 per year in the hospital studied. Use of a disinfectant cap on IV needleless connectors in addition to an existing standard central line bundle was associated with decreased CLABSI and costs. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Infection and colonization by Gram-negative bacilli in neonates hospitalized in High Risk Nursery at Uberlandia Federal University Hospital: etiology, resistant phenotypes and risk factors Infecção e colonização por bacilos Gram-negativos em neonatos internados em Berçário de Alto Risco do Hospital da Universidade Federal de Uberlândia: etiologia, fenótipos de resistência e fatores de risco

Directory of Open Access Journals (Sweden)

Renata Cristina Cezário

2004-09-01

Full Text Available The aims of this study were to determine endemic and epidemic infection due to Gram-negative bacilli, risk factors associated with colonization and infection by these organisms and the resistance phenotypes (ESBL, AmpC in neonates admitted in a High Risk Nursery. The study was conducted during a 21 month period and included: a prospective study to evaluate the neonates with hospital infection and the use of third-generation cephalosporins; a case-control study to determine the risk factors associated with colonization/infection. Rectal and oropharynx cultures were also performed in four opportunities (September and November 2001, February and August 2002. The isolates for which the resistance of ceftazidime was 2 mg/mL were suspected of producing ESBL or AmpC b-lactamases. The incidence of infection by Gram-negative bacilli was 2.4% (89/3.708 neonates, and sepsis (35.9% and conjunctivitis (31.4% were the most common infections. The endemic infections were more prevalent (73.9% and usually associated with Enterobacteriaceae (95.5%, being these organisms also related to colonization, corresponding mainly to isolates of Enterobacter spp. and Klebsiella spp. Two outbreaks of Pseudomonas aeruginosa (n=10 and Acinetobacter baumannii (n=11 were identified during the survey. Univariate analysis showed that risk factors for Gram-negative bacilli infection considered significant included: the length of stay before infection/colonization, exposure to antimicrobial agents, mechanical ventilation, central venous catheters, parenteral nutrition and surgery. The majority of resistance to ceftazidime among Enterobacteriaceae isolates (80.9% was from ESBL phenotype. Administration of third-generation cephalosporins (ceftriaxone led to the emergence of these multiresistant Gram-negative bacilli in the neonatal unit.Os objetivos deste estudo foram determinar infecções endêmicas e epidêmicas por bacilos Gram-negativos, fatores de risco associados a coloniza

Long-term adherence to a 5 day antibiotic course guideline for treatment of intensive care unit (ICU)-associated Gram-negative infections.

Science.gov (United States)

Edgeworth, Jonathan D; Chis Ster, Irina; Wyncoll, Duncan; Shankar-Hari, Manu; McKenzie, Catherine A

2014-06-01

To determine long-term adherence to a 5 day antibiotic course guideline for treating intensive care unit (ICU)-acquired Gram-negative bacteria (GNB) infections. Descriptive analysis of patient-level data on all GNB-active antibiotics prescribed from day 3 and all GNB identified in clinical samples in 5350 patients admitted to a 30 bed general ICU between 2002 and 2009. Four thousand five hundred and eleven of 5350 (84%) patients were treated with one or more antibiotics active against GNB commenced from day 3. Gentamicin was the most frequently prescribed antibiotic (92.2 days of therapy/1000 patient-days). Only 6% of courses spanned >6 days of therapy and 89% of antibiotic therapy days were with a single antibiotic active against GNB. There was no significant difference between gentamicin and meropenem in the number of first courses in which a resistant GNB was identified in blood cultures [11/1177 (0.9%) versus 5/351 (1.4%); P = 0.43] or respiratory tract specimens [59/951 (6.2%) versus 17/246 (6.9%); P = 0.68] at the time of starting therapy. This study demonstrates long-term adherence to a 5 day course antibiotic guideline for treatment of ICU-associated GNB infections. This guideline is a potential antibiotic-sparing alternative to currently recommended dual empirical courses extending to ≥7 days. © 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: journals.permissions@oup.com.

Expression levels of matrix metalloproteinase-9 and gram-negative bacteria in symptomatic and asymptomatic periapical lesions.

Science.gov (United States)

Ahmed, Geraldine M; El-Baz, Alaa A; Hashem, Ahmed Abdel Rahman; Shalaan, Abeer K

2013-04-01

The aim of this study was to test the hypothesis that the expression of matrix metalloproteinase (MMP)-9 is significantly elevated in patients with symptomatic apical periodontitis and to correlate this with the detected amount of gram-negative bacteria. Twenty-six patients with periapical lesions involving at least 2 teeth were included in this study. The patients were divided into 2 groups: the symptomatic (SYM) group included 13 patients expressing pain with periapical lesions, and the asymptomatic (ASYM) group included 13 patients expressing no pain. Root canal treatment was performed followed by endodontic surgery and periapical lesion collection. Periapical lesions were serially cut into 4-μ sections. Some sections were processed for histologic examination using hematoxylin-eosin stain. Other sections were processed for immunohistochemical examination. For MMP-9, the area fraction of the positive cells was measured, and the percentage of the MMP-9-immunopositive area to the total area of the microscopic field was calculated. For gram-negative stain cells, the number of cells showing the pink-red color was counted per microscopic field. The Student's t test was used to compare the SYM and ASYM groups. The Pearson correlation coefficient was used to determine a significant correlation between the number of cells and the MMP-9 level. The significance level was set at P ≤ .05. The SYM group showed a statistically significantly higher mean number of gram-negative cells (P = .001) and MMP-9 area percent (P < .001) than the ASYM group. There was a statistically significant positive (r = .927) correlation between the number of gram-negative cells and the MMP-9 area percent (P< .001). There is good evidence to suspect a significant role of gram-negative bacteria and MMP-9 in symptomatic periapical lesions. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria.

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Kidd, James M; Kuti, Joseph L; Nicolau, David P

2018-03-01

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.

Is the gram stain useful in the microbiologic diagnosis of VAP? A meta-analysis.

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O'Horo, John C; Thompson, Deb; Safdar, Nasia

2012-08-01

In a meta-analysis examining respiratory specimen Gram stain for diagnosis of ventilator-associated pneumonia, absence of bacteria on Gram stain had a high negative predictive value, but a positive Gram stain correlated poorly with organisms recovered in culture. Rapid and accurate diagnosis of ventilator-associated pneumonia (VAP) is a major challenge and no generally accepted gold standard exists for VAP diagnosis. We conducted a meta-analysis to examine the role of respiratory specimen Gram stain to diagnose VAP, and the correlation with final culture results. In 21 studies, pooled sensitivity of Gram stain for VAP was 0.79 (95% confidence interval [CI], .77-0.81; P Gram stain for a VAP prevalence of 20%-30% was 91%, suggesting that VAP is unlikely with a negative Gram stain but the positive predictive value of Gram stain was only 40%. Pooled kappa was 0.42 for gram-positive organisms and 0.34 for gram-negative organisms, suggesting fair concordance between organisms on Gram stain and recovery by culture. Therefore, a positive Gram stain should not be used to narrow anti-infective therapy until culture results become available.

Neonatal blood stream infections in tertiary referral hospitals in Kurdistan, Iran.

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Nikkhoo, Bahram; Lahurpur, Fariba; Delpisheh, Ali; Rasouli, Mohammad Aziz; Afkhamzadeh, Abdorrahim

2015-06-09

Bloodstream infection (BSI) is one of the most common causes of nosocomial infection in neonatal intensive care units (NICU). The aim of the present study was to determine bacterial agents and their susceptibility patterns to antibiotics and to investigate the risk factors associated with BSI. This was a nested case-control study carried out from September 2009 to June 2010 in the NICU wards in Sanandaj hospitals western Iran. Cases were patients with BSI and controls were other patients who had negative blood culture. Bacteriologic diagnosis and antibiotic susceptibility pattern was performed based on the Edward & Ewings and the National Committee of Clinical Laboratory (NCCL) Standards. Of 472 patients who hospitalized in NICU, 6.4% had BSI (n = 30) including 17girls (56.7%) and 13 boys (43.3%). Enterobacter SPP was the predominant isolated bacteria from blood culture (36.7%). The maximum antibiotic resistance and sensitivity were observed by Tetracycline and Ciprofloxacin respectively. Risk factors associated with BSI were age ≤ 7 days (p = 0.001), previous antibiotic consumption (p = 0.013), and low birth weight (LBW), (p = 0.001). Gram negative bacteria and Entrobacter in particular are the most common pathogens. Improving prenatal health care, standards of infection control and choosing accurate antibiotics are recommended to avoid BSI in neonatal intensive care units.

High resistance rate against 15 different antibiotics in aerobic gram-negative bacteria isolates of cardiology intensive care unit patients

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Küçükates E

2002-01-01

Full Text Available Aerobic gram negative bacteria were isolated and examined microbiologically from various clinical samples of 602 patients hospitalized between January 1997 and December 2000 in surgical and coronary intensive care units (ICUs. A total of 827 isolates were obtained from 602 patients. The majority of microorganisms were isolated from the respiratory tract (50.3% and blood (39.9%. Pseudomonas spp. were the most frequently isolated gram negative species (32.7%, followed by Acinetobacter spp. (24.0% and Klebsiella pneumoniae (19.4%. High resistance rates to all antibiotics studied were observed. Imipenem and meropenem were the most effective antibiotics against gram negatives.

Effect of silver/copper and copper oxide nanoparticle powder on growth of Gram-negative and Gram-positive bacteria and their toxicity against the normal human dermal fibroblasts

International Nuclear Information System (INIS)

Peszke, Jerzy; Nowak, Anna; Szade, Jacek; Szurko, Agnieszka; Zygadło, Dorota; Michałowska, Marlena; Krzyściak, Paweł; Zygoń, Patrycja; Ratuszna, Alicja; Ostafin, Marek M.

2016-01-01

Engineered nanomaterials, especially metallic nanoparticles, are the most popular system applied in daily life products. The study of their biological and toxicity properties seems to be indispensable. In this paper, we present results of biological activity of Ag/Cu nanoparticles. These nanoparticles show more promising killing/inhibiting properties on Gram-negative bacteria than for Gram-positive ones. The Gram-negative bacteria show strong effect already at the concentration of 1 ppm after 15 min of incubation. Moreover, in vitro tests of toxicity made on normal human dermal fibroblast cultures showed that after 72 h of incubation with Ag/Cu nanoparticles, they are less toxic then Cu 2 O/CuO nanoparticles.

Effect of silver/copper and copper oxide nanoparticle powder on growth of Gram-negative and Gram-positive bacteria and their toxicity against the normal human dermal fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Peszke, Jerzy; Nowak, Anna, E-mail: ana.maria.nowak@gmail.com; Szade, Jacek; Szurko, Agnieszka; Zygadło, Dorota; Michałowska, Marlena [University of Silesia, A. Chelkowski Institute of Physics (Poland); Krzyściak, Paweł [Jagiellonian University Medical College, Department of Mycology Chair of Microbiology (Poland); Zygoń, Patrycja [Czestochowa University of Technology, Institute of Materials Engineering (Poland); Ratuszna, Alicja [University of Silesia, A. Chelkowski Institute of Physics (Poland); Ostafin, Marek M. [Department of Microbiology University of Agriculture (Poland)

2016-12-15

Engineered nanomaterials, especially metallic nanoparticles, are the most popular system applied in daily life products. The study of their biological and toxicity properties seems to be indispensable. In this paper, we present results of biological activity of Ag/Cu nanoparticles. These nanoparticles show more promising killing/inhibiting properties on Gram-negative bacteria than for Gram-positive ones. The Gram-negative bacteria show strong effect already at the concentration of 1 ppm after 15 min of incubation. Moreover, in vitro tests of toxicity made on normal human dermal fibroblast cultures showed that after 72 h of incubation with Ag/Cu nanoparticles, they are less toxic then Cu{sub 2}O/CuO nanoparticles.

An unusual class of anthracyclines potentiate Gram-positive antibiotics in intrinsically resistant Gram-negative bacteria

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Cox, Georgina; Koteva, Kalinka; Wright, Gerard D.

2014-01-01

Objectives An orthogonal approach taken towards novel antibacterial drug discovery involves the identification of small molecules that potentiate or enhance the activity of existing antibacterial agents. This study aimed to identify natural-product rifampicin adjuvants in the intrinsically resistant organism Escherichia coli. Methods E. coli BW25113 was screened against 1120 actinomycete fermentation extracts in the presence of subinhibitory (2 mg/L) concentrations of rifampicin. The active molecule exhibiting the greatest rifampicin potentiation was isolated using activity-guided methods and identified using mass and NMR spectroscopy. Susceptibility testing and biochemical assays were used to determine the mechanism of antibiotic potentiation. Results The anthracycline Antibiotic 301A1 was isolated from the fermentation broth of a strain of Streptomyces (WAC450); the molecule was shown to be highly synergistic with rifampicin (fractional inhibitory concentration index = 0.156) and moderately synergistic with linezolid (FIC index = 0.25) in both E. coli and Acinetobacter baumannii. Activity was associated with inhibition of efflux and the synergistic phenotype was lost when tested against E. coli harbouring mutations within the rpoB gene. Structure–activity relationship studies revealed that other anthracyclines do not synergize with rifampicin and removal of the sugar moiety of Antibiotic 301A1 abolishes activity. Conclusions Screening only a subsection of our natural product library identified a small-molecule antibiotic adjuvant capable of sensitizing Gram-negative bacteria to antibiotics to which they are ordinarily intrinsically resistant. This result demonstrates the great potential of this approach in expanding antibiotic effectiveness in the face of the growing challenge of resistance in Gram-negatives. PMID:24627312

A cardiac implantable device infection by Raoultella planticola in an immunocompromized patient.

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Adjodah, Chandra; D'Ivernois, Chistophe; Leyssene, David; Berneau, Jean-Baptiste; Hemery, Yann

2017-02-01

Introduction. Infection of cardiac implantable electronic devices is a severe condition associated with high mortality, particularly in patients who are dependent upon heart-pacing devices. Staphylococci are found in 70 % of reported cases. Case presentation. We report the case of a cardiac-pacemaker infection in a 79-year-old man, cumulating a history of rheumatoid arthritis treated by corticosteroids and methotrexate by a recently identified micro-organism: Raoultella planticola . He presented local signs of infection on his VVI pacemaker implantation site and underwent urgent pocket device replacement under cefamandole antibioprophylaxis. On incision thick pus oozed out. It was necessary to perform a complete hardware extraction comprising the pulse generator and the ancient lead. Pus was inoculated into aerobic and anaerobic culture vials and Gram staining unveiled Gram-negative rods. Microbiology analysis identified the organism as R. planticola. A new pacing device was inserted on the contrlateral pectoral region. Ciprofloxacin enabled full recovery. A literature review concerning this pathogen revealed that it is involved in severe infections such as bloodstream infections, peritonitis, cellulitis, pneumonia and lung abscesses, and urinary tract infections. In these case reports, underlying co-morbidities were identified such as solid active neoplasia, recent chemotherapy, corticosteroids, solid-organ-recipient patients and recent open surgery. Conclusion. R. planticola is a serious emerging pathogen and contributes to the burden of various infectious conditions. Its pathogenicity and occurrence should be known by clinicians and a high level of awareness is necessary to precisely identify it provide the correct antibiotic regimen.

Development of Quorum-Based Anti-Virulence Therapeutics Targeting Gram-Negative Bacterial Pathogens

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Wen Shan Yew

2013-08-01

Full Text Available Quorum sensing is a cell density-dependent signaling phenomenon used by bacteria for coordination of population-wide phenotypes, such as expression of virulence genes, antibiotic resistance and biofilm formation. Lately, disruption of bacterial communication has emerged as an anti-virulence strategy with enormous therapeutic potential given the increasing incidences of drug resistance in pathogenic bacteria. The quorum quenching therapeutic approach promises a lower risk of resistance development, since interference with virulence generally does not affect the growth and fitness of the bacteria and, hence, does not exert an associated selection pressure for drug-resistant strains. With better understanding of bacterial communication networks and mechanisms, many quorum quenching methods have been developed against various clinically significant bacterial pathogens. In particular, Gram-negative bacteria are an important group of pathogens, because, collectively, they are responsible for the majority of hospital-acquired infections. Here, we discuss the current understanding of existing quorum sensing mechanisms and present important inhibitory strategies that have been developed against this group of pathogenic bacteria.

Lipopolysaccharide biogenesis and transport at the outer membrane of Gram-negative bacteria.

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Sperandeo, Paola; Martorana, Alessandra M; Polissi, Alessandra

2017-11-01

The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer containing a unique glycolipid, lipopolysaccharide (LPS) in its outer leaflet. LPS molecules confer to the OM peculiar permeability barrier properties enabling Gram-negative bacteria to exclude many toxic compounds, including clinically useful antibiotics, and to survive harsh environments. Transport of LPS poses several problems to the cells due to the amphipatic nature of this molecule. In this review we summarize the current knowledge on the LPS transport machinery, discuss the challenges associated with this process and present the solutions that bacterial cells have evolved to address the problem of LPS transport and assembly at the cell surface. Finally, we discuss how knowledge on LPS biogenesis can be translated for the development of novel antimicrobial therapies. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016. Published by Elsevier B.V.

Multiparametric Profiling for Identification of Chemosensitizers against Gram-Negative Bacteria

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Vincent Lôme

2018-02-01

Full Text Available Antibiotic resistance is now a worldwide therapeutic problem. Since the beginning of anti-infectious treatment bacteria have rapidly shown an incredible ability to develop and transfer resistance mechanisms. In the last decades, the design variation of pioneer bioactive molecules has strongly improved their activity and the pharmaceutical companies partly won the race against the clock. Since the 1980s, the new classes of antibiotics that emerged were mainly directed to Gram-positive bacteria. Thus, we are now facing to multidrug-resistant Gram-negative bacteria, with no therapeutic options to deal with them. These bacteria are mainly resistant because of their double membrane that conjointly impairs antibiotic accumulation and extrudes these molecules when entered. The main challenge is to allow antibiotics to cross the impermeable envelope and reach their targets. One promising solution would be to associate, in a combination therapy, a usual antibiotic with a non-antibiotic chemosensitizer. Nevertheless, for effective drug discovery, there is a prominent lack of tools required to understand the rules of permeation and accumulation into Gram-negative bacteria. By the use of a multidrug-resistant enterobacteria, we introduce a high-content screening procedure for chemosensitizers discovery by quantitative assessment of drug accumulation, alteration of barriers, and deduction of their activity profile. We assembled and analyzed a control chemicals library to perform the proof of concept. The analysis was based on real-time monitoring of the efflux alteration and measure of the influx increase in the presence of studied compounds in an automatized bio-assay. Then, synergistic activity of compounds with an antibiotic was studied and kinetic data reduction was performed which led to the calculation of a score for each barrier to be altered.

Comparative activity of carbapenem testing (the COMPACT study in Turkey

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Leblebicioglu Hakan

2012-02-01

Full Text Available Abstract Background Recent evidence indicates that Gram-negative bacterial pathogens, the most common of which are Pseudomonas spp., Enterobacteriaceae, and Acinetobacter baumannii, are frequent causes of hospital-acquired infections. This study aims to evaluate the in vitro activity of doripenem and comparator carbapenem antibiotics against Gram-negative clinical isolates collected from COMParative Activity of Carbapenem Testing (COMPACT study centres in Turkey. Methods Ten centres in Turkey were invited to submit Pseudomonas aeruginosa, Enterobacteriaceae, and other Gram-negative isolates from intensive care unit (ICU/non-ICU patients with complicated intra-abdominal infections, bloodstream infections, or nosocomial pneumonia, including ventilator-associated pneumonia, between May and October 2008. Susceptibility was determined by each centre using E-test. A central laboratory performed species confirmation as well as limited susceptibility and quality-control testing. Results Five hundred and ninety six isolates were collected. MIC90 values for doripenem, meropenem, and imipenem, respectively, were 32, ≥ 64, and ≥ 64 mg/L against Pseudomonas spp.; 0.12, 0.12, and 0.5 mg/L against Enterobacteriaceae; and ≥ 64 mg/L for each against other Gram-negative isolates. In determining the susceptibility of hospital isolates of selected Gram-negative pathogens to doripenem, imipenem, and meropenem, we found that against all pathogens combined, the MIC90 for ICU compared with non-ICU isolates was higher. Conclusions Doripenem showed similar or slightly better activity than meropenem and better activity than imipenem against the Gram-negative pathogens collected in Turkey.

Clinical manifestations and management of left ventricular assist device-associated infections.

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Nienaber, Juhsien Jodi C; Kusne, Shimon; Riaz, Talha; Walker, Randall C; Baddour, Larry M; Wright, Alan J; Park, Soon J; Vikram, Holenarasipur R; Keating, Michael R; Arabia, Francisco A; Lahr, Brian D; Sohail, M Rizwan

2013-11-01

Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

Facilitating central line-associated bloodstream infection prevention: a qualitative study comparing perspectives of infection control professionals and frontline staff.

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McAlearney, Ann Scheck; Hefner, Jennifer L

2014-10-01

Infection control professionals (ICPs) play a critical role in implementing and managing healthcare-associated infection reduction interventions, whereas frontline staff are responsible for delivering direct and ongoing patient care. The objective of our study was to determine if ICPs and frontline staff have different perspectives about the facilitators and challenges of central line-associated bloodstream infection (CLABSI) prevention program success. We conducted key informant interviews at 8 hospitals that participated in the Agency for Healthcare Research and Quality CLABSI prevention initiative called "On the CUSP: Stop BSI." We analyzed interview data from 50 frontline nurses and 26 ICPs to identify common themes related to program facilitators and challenges. We identified 4 facilitators of CLABSI program success: education, leadership, data, and consistency. We also identified 3 common challenges: lack of resources, competing priorities, and physician resistance. However, the perspective of ICPs and frontline nurses differed. Whereas ICPs tended to focus on general descriptions, frontline staff noted program specifics and often discussed concrete examples. Our results suggest that ICPs need to take into account the perspectives of staff nurses when implementing infection control and broader quality improvement initiatives. Further, the deliberate inclusion of frontline staff in the implementation of these programs may be critical to program success. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis.

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Jung, Chiau-Jing; Zheng, Quan-Hau; Shieh, Ya-Hsiung; Lin, Chi-Shuan; Chia, Jean-San

2009-11-01

Streptococcus mutans, a commensal of the human oral cavity, can survive in the bloodstream and cause infective endocarditis (IE). However, the virulence factors associated with this manifestation of disease are not known. Here, we demonstrate that AtlA, an autolysin of S. mutans is a newly identified fibronectin (Fn) binding protein and contributes to bacterial resistance to phagocytosis and survival in the bloodstream. Interestingly, prior exposure to plasma at low concentrations was sufficient to enhance bacterial survival in the circulation. Calcium ions at physiological plasma concentrations induced maturation of AtlA from the 104-90 kDa isoform resulting in increased Fn binding and resistance to phagocytosis. An isogenic mutant strain defective in AtlA expression exhibited reduced survival and virulence when tested in a rat model of IE compared with the wild-type and complemented strains. The data presented suggest that plasma components utilized by S. mutans enhanced survival in the circulation and AtlA is a virulence factor associated with infective endocarditis.

Synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria

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Talei, Gholam-Reza; Mohammadi, Mohsen; Bahmani, Mahmoud; Kopaei, Mahmoud Rafieian

2017-01-01

Background: Infectious diseases have always been an important health issue in human communities. In the recent years, much research has been conducted on antimicrobial effects of nature-based compounds because of increased prevalence of antibiotic resistance. The present study was conducted to investigate synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria. Materials and Methods: In this experimental study, the synergistic effects of C. copticum and M. piperita essential oils with antibiotics on Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus epidermidis (ATCC 14990), and Listeria monocytogenes (ATCC 7644) were studied according to broth microdilution and the MIC and fractional inhibitory concentration (FIC) of these two essential oils determined. Results: C. copticum essential oil at 30 μg/ml could inhibit S. aureus, and in combination with vancomycin, decreased MIC from 0.5 to 0.12 μg/ml. Moreover, the FIC was derived 0.24 μg/ml which represents a potent synergistic effect with vancomycin against S. aureus growth. C. copticum essential oil alone or combined with other antibiotics is effective in treating bacterial infections. Conclusions: In addition, C. copticum essential oil can strengthen the activities of certain antibiotics, which makes it possible to use this essential oil, especially in drug resistance or to lower dosage or toxicity of the drugs. PMID:28929050

Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation.

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Forcina, Alessandra; Lorentino, Francesca; Marasco, Vincenzo; Oltolini, Chiara; Marcatti, Magda; Greco, Raffaella; Lupo-Stanghellini, Maria Teresa; Carrabba, Matteo; Bernardi, Massimo; Peccatori, Jacopo; Corti, Consuelo; Ciceri, Fabio

2018-03-02

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Three-hundred forty-eight consecutive patients transplanted at our hospital from July 2012 to January 2016 were screened for a pretransplant MDR-GNB colonization and evaluated for clinical outcomes. A pretransplant MDR-GNB colonization was found in 16.9% of allo-HSCT and in 9.6% of auto-HSCT recipients. Both in auto- and in allo-HSCT, carriers of a MDR-GNB showed no significant differences in overall survival (OS), transplant-related mortality (TRM), or infection-related mortality (IRM) compared with noncarriers. OS at 2 years for carriers compared with noncarriers was 85% versus 81% (P = .262) in auto-HSCT and 50% versus 43% (P = .091) in allo-HSCT. TRM at 2 years was 14% versus 5% (P = .405) in auto-HSCT and 31% versus 25% (P = .301) in allo-HSCT. IRM at 2 years was 14% versus 2% (P = .142) in auto-HSCT and 23% versus 14% (P = .304) in allo-HSCT. In multivariate analysis, only grade III to IV acute graft-versus-host disease was an independent factor for reduced OS (P < .001) and increased TRM (P < .001) and IRM (P < .001). During the first year after transplant, we collected 73 GNB bloodstream infectious (BSI) episodes in 54 patients, 42.4% of which sustained by a MDR-GNB. Rectal swabs positivity associated with the pathogen causing subsequent MDR-GNB BSI episodes in 13 of 31 (41.9%). Overall, OS at 4 months from MDR-GNB BSI episode onset was of 67.9%, with a 14-day attributed mortality of 12.9%, not being significantly different between carriers and noncarriers (P = .207). We conclude that in this extended single-center experience, a pretransplant MDR-GNB colonization did not significantly influence OS, TRM, and IRM both in auto- and allo-HSCT settings and that MDR-GNB attributed mortality can be controlled in carriers when an early pre-emptive antimicrobial therapy is

Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

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Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

2017-05-23

The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Clinical study of carbapenem sensitive and resistant Gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India.

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Ghafur, A K; Vidyalakshmi, P R; Kannaian, P; Balasubramaniam, R

2014-01-01

Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram-negative bacteremia, identified over a period of 1-year was done by medical records review, in Apollo Specialty Hospital, a 300-bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. Of the total 141 patients with Gram-negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia.

Incidence of colonization and bloodstream infection with carbapenem-resistant Enterobacteriaceae in children receiving antineoplastic chemotherapy in Italy.

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Caselli, Desiree; Cesaro, Simone; Fagioli, Franca; Carraro, Francesca; Ziino, Ottavio; Zanazzo, Giulio; Meazza, Cristina; Colombini, Antonella; Castagnola, Elio

2016-02-01

Few data are available on the incidence of carbapenemase-producing Enterobacteriaceae (CPE) infection or colonization in children receiving anticancer chemotherapy. We performed a nationwide survey among centers participating in the pediatric hematology-oncology cooperative study group (Associazione Italiana Ematologia Oncologia Pediatrica, AIEOP). During a 2-year observation period, we observed a threefold increase in the colonization rate, and a fourfold increase of bloodstream infection episodes, caused by CPE, with a 90-day mortality of 14%. This first nationwide Italian pediatric survey shows that the circulation of CPE strains in the pediatric hematology-oncology environment is increasing. Given the mortality rate, which is higher than for other bacterial strains, specific monitoring should be applied and the results should have implications for health-care practice in pediatric hematology-oncology.

Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria

NARCIS (Netherlands)

Kikkert, R.; Laine, M. L.; Aarden, L. A.; van Winkelhoff, A. J.

2007-01-01

BACKGROUND/AIMS: Periodontitis is a chronic infectious disease associated with a gram-negative subgingival microflora. Bacterial components stimulate, among other receptors, Toll-like receptor (TLR) 2 and/or TLR4. Accumulating evidence indicates that both qualitatively and quantitatively distinct

Silver-doped manganese dioxide and trioxide nanoparticles inhibit both gram positive and gram negative pathogenic bacteria.

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Kunkalekar, R K; Prabhu, M S; Naik, M M; Salker, A V

2014-01-01

Palladium, ruthenium and silver-doped MnO2 and silver doped Mn2O3 nanoparticles were synthesized by simple co-precipitation technique. SEM-TEM analysis revealed the nano-size of these synthesized samples. XPS data illustrates that Mn is present in 4+ and 3+ oxidation states in MnO2 and Mn2O3 respectively. Thermal analysis gave significant evidence for the phase changes with increasing temperature. Antibacterial activity of these synthesized nanoparticles on three Gram positive bacterial cultures (Staphylococcus aureus ATCC 6538, Streptococcus epidermis ATCC 12228, Bacillus subtilis ATCC 6633) and three Gram negative cultures (Escherichia coli ATCC 8739, Salmonella abony NCTC 6017 and Klebsiella pneumoniae ATCC 1003) was investigated using a disc diffusion method and live/dead assay. Only Ag-doped MnO2 and Ag-doped Mn2O3 nanoparticles showed antibacterial property against all six-test bacteria but Ag-doped MnO2 was found to be more effective than Ag-doped Mn2O3. Copyright © 2013 Elsevier B.V. All rights reserved.

Risk factors and mortality for nosocomial bloodstream infections in elderly patients.

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Reunes, S; Rombaut, V; Vogelaers, D; Brusselaers, N; Lizy, C; Cankurtaran, M; Labeau, S; Petrovic, M; Blot, S

2011-10-01

To determine risk factors for nosocomial bloodstream infection (BSI) and associated mortality in geriatric patients in geriatric and internal medicine wards at a university hospital. Single-center retrospective (1992-2007), pairwise-matched (1:1-ratio) cohort study. Geriatric patients with nosocomial BSI were matched with controls without BSI on year of admission and length of hospitalization before onset of BSI. Demographic, microbiological, and clinical data are collected. One-hundred forty-two BSI occurred in 129 patients. Predominant microorganisms were Escherichia coli (23.2%), coagulase-negative Staphylococci (19.4%), Pseudomonas aeruginosa (8.4%), Staphylococcus aureus (7.1%), Klebsiella pneumoniae (5.8%) and Candida spp. (5.8%). Matching was successful for 109 cases. Compared to matched control subjects, cases were more frequently female, suffered more frequently from arthrosis, angina pectoris and pressure ulcers, had worse Activities of Daily Living-scores, had more often an intravenous or bladder catheter, and were more often bedridden. Logistic regression demonstrated presence of an intravenous catheter (odds ratio [OR] 7.5, 95% confidence interval [CI] 2.5-22.9) and being bedridden (OR 2.9, 95% CI 1.6-5.3) as independent risk factors for BSI. In univariate analysis nosocomial BSI was associated with increased mortality (22.0% vs. 11.0%; P=0.029). After adjustment for confounding co-variates, however, nosocomial BSI was not associated with mortality (hazard ratio 1.3, 95% CI 0.6-2.6). Being bedridden and increasing age were independent risk factors for death. Intravenous catheters and being bedridden are the main risk factors for nosocomial BSI. Although associated with higher mortality, this infectious complication seems not to be an independent risk factor for death in geriatric patients. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Catheter-free Period Over 2 Days Is Associated with Better Outcome in Catheter-related Bloodstream Infection due to Candida

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Matsuo, Takahiro; Mori, Nobuyoshi; Hoshino, Eri; Sakurai, Aki; Furukawa, Keiichi

2017-01-01

Abstract Background Regardless of active antifungal drugs, mortality of candidemia remains high. Although it is well-known that central venous catheter (CVC) is one of the most important risk factors of candidemia and should be removed immediately, little is known about optimal timing of CVC replacement after removal. Here, we analyzed contributing risk factors associated with 30-day mortality for catheter-related bloodstream infection (CRBSI) due to candida and optimal timing of CVC replacem...

Analisi delle antibiotico-resistenze di Gram-negativi isolati da pazienti con infezioni del tratto urinario afferenti al Polo Oncologico e Dermatologico I.F.O.

OpenAIRE

Maria Teresa Gallo; Grazia Prignano; Mauro Belardi; Karim Donato; Gian Piero Testore; Fabrizio Ensoli

2006-01-01

Introduction. Urinary tract infections represent a worlwide problem due to their prevalence among nosocomial infections and to the increasing frequency of antibiotic resistance among the Gram-negative pathogens. Knowledge of the antimicrobial resistance patterns according to local epidemiology is essential for providing clinically appropriate therapy for urinary tract infection. In the present study we analysed the drug resistence pattern of Gram negative bacteria isolated from urine samples ...

Survival and detection of coliforms, Enterobacteriaceae, and gram-negative bacteria in Greek yogurt.

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Hervert, C J; Martin, N H; Boor, K J; Wiedmann, M

2017-02-01

Despite the widespread use of coliforms as indicator bacteria, increasing evidence suggests that the Enterobacteriaceae (EB) and total gram-negative groups more accurately reflect the hygienic status of high-temperature, short-time pasteurized milk and processing environments. If introduced into milk as postpasteurization contamination, these bacteria may grow to high levels and produce a wide range of sensory-related defects. However, limited information is available on the use and survival of bacterial hygiene indicators in dairy products outside of pasteurized fluid milk and cheese. The goal of this study was to (1) provide information on the survival of a diverse set of bacterial hygiene indicators in the low pH environment of Greek yogurt, (2) compare traditional and alternative detection methods for their ability to detect bacterial hygiene indicators in Greek yogurt, and (3) offer insight into optimal hygiene indicator groups for use in low-pH fermented dairy products. To this end, we screened 64 bacterial isolates, representing 24 dairy-relevant genera, for survival and detection in Greek yogurt using 5 testing methods. Before testing, isolates were inoculated into plain, 0% fat Greek yogurt (pH 4.35 to 4.65), followed by a 12-h hold period at 4 ± 1°C. Yogurts were subsequently tested using Coliform Petrifilm (3M, St. Paul, MN) to detect coliforms; Enterobacteriaceae Petrifilm (3M), violet red bile glucose agar and the D-Count (bioMérieux, Marcy-l'Étoile, France) to detect EB; and crystal violet tetrazolium agar (CVTA) to detect total gram-negative bacteria. Overall, the non-EB gram-negative isolates showed significantly larger log reductions 12 h after inoculation into Greek yogurt (based on bacterial numbers recovered on CVTA) compared with the coliform and noncoliform EB isolates tested. The methods evaluated varied in their ability to detect different microbial hygiene indicators in Greek yogurt. Crystal violet tetrazolium agar detected the highest

O-antigen protects gram-negative bacteria from histone killing.

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Catherine Chaput

Full Text Available Beyond their traditional role of wrapping DNA, histones display antibacterial activity to Gram-negative and -positive bacteria. To identify bacterial components that allow survival to a histone challenge, we selected resistant bacteria from homologous Escherichia coli libraries that harbor plasmids carrying pieces of the chromosome in different sizes. We identified genes required for exopolysaccharide production and for the synthesis of the polysaccharide domain of the lipopolysaccharide, called O-antigen. Indeed, O-antigen and exopolysaccharide conferred further resistance to histones. Notably, O-antigen also conferred resistance to histones in the pathogens Shigella flexneri and Klebsiella pneumoniae.

Non-oral gram-negative facultative rods in chronic periodontitis microbiota.

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van Winkelhoff, Arie J; Rurenga, Patrick; Wekema-Mulder, Gepke J; Singadji, Zadrach M; Rams, Thomas E

2016-05-01

The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. Subgingival biofilm specimens from 102 untreated and 101 recently treated adults with chronic periodontitis in the Netherlands were plated onto MacConkey III and Dentaid selective media with air-5% CO2 incubation for isolation of non-oral GNFR, and onto enriched Oxoid blood agar with anaerobic incubation for recovery of selected periodontal bacterial pathogens. Suspected non-oral GNFR clinical isolates were identified to a species level with the VITEK 2 automated system. A total of 87 (42.9%) out of 203 patients yielded subgingival non-oral GNFR. Patients recently treated with periodontal mechanical debridement therapy demonstrated a greater prevalence of non-oral GNFR (57.4% vs 28.4%, P chronic periodontitis patients yielded cultivable non-oral GNFR in periodontal pockets, particularly among those recently treated with periodontal mechanical debridement therapy. Since non-oral GNFR species may resist mechanical debridement from periodontal pockets, and are often not susceptible to many antibiotics frequently used in periodontal practice, their subgingival presence may complicate periodontal treatment in species-positive patients and increase risk of potentially dangerous GNFR infections developing at other body sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience

OpenAIRE

Galloway, David; Danziger-Isakov, Lara; Goldschmidt, Monique; Hemmelgarn, Trina; Courter, Joshua; Nathan, Jaimie D.; Alonso, Maria; Tiao, Greg; Fei, Lin; Kocoshis, Samuel

2015-01-01

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, ...

Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis

DEFF Research Database (Denmark)

Lilje, Berit; Rasmussen, Rasmus Vedby; Dahl, Anders

2017-01-01

Most Staphylococcus aureus isolates can cause invasive disease given the right circumstances, but it is unknown if some isolates are more likely to cause severe infections than others. S. aureus bloodstream isolates from 120 patients with definite infective endocarditis and 121 with S. aureus...... bacteraemia without infective endocarditis underwent whole-genome sequencing. Genome-wide association analysis was performed using a variety of bioinformatics approaches including SNP analysis, accessory genome analysis and k-mer based analysis. Core and accessory genome analyses found no association...... with either of the two clinical groups. In this study, the genome sequences of S. aureus bloodstream isolates did not discriminate between bacteraemia and infective endocarditis. Based on our study and the current literature, it is not convincing that a specific S. aureus genotype is clearly associated...

Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit

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Orlei Ribeiro de Araujo

Full Text Available Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU, would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396 comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349 were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004 and in Group 3 (n=250 when cefepime was reintroduced (January to September 2005. Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017 and Group 3 (p=0.003. There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.

A Trojan-Horse Strategy Including a Bacterial Suicide Action for the Efficient Use of a Specific Gram-Positive Antibiotic on Gram-Negative Bacteria.

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Schalk, Isabelle J

2018-05-10

In the alarming context of rising bacterial antibiotic resistance, there is an urgent need to discover new antibiotics or increase and/or enlarge the activity of those currently in use. The need for new antibiotics is even more urgent in the case of Gram-negative bacteria, such as Acinetobacter, Pseudomonas, and Enterobacteria, which have become resistant to many antibiotics and have an outer membrane with very low permeability to drugs. Vectorization of antibiotics using siderophores may be a solution to bypass such a bacterial wall: the drugs use the iron transporters of the outer membrane as gates to enter bacteria in a Trojan-horse strategy. Designing siderophore-antibiotics that can cross outer membranes has become almost routine, but their transport across the inner membrane is still a limiting step, as well as a strategy that allows dissociation of the antibiotic from the siderophore once inside the bacteria. Liu et al. ( J. Med. Chem. 2018 , DOI: 10.1021/acs.jmedchem.8b00218 ) report the synthesis of a siderophore-cephalosporin compound and demonstrate that β-lactams, such as cephalosporins, can serve as β-lactamase-triggered releasable linkers to allow intracellular delivery of Gram-positive antibiotics to Gram-negative bacteria.

The gram-negative bacterial periplasm: Size matters.

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Samuel I Miller

2018-01-01

Full Text Available Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the cytoplasm whose distinct reducing environment allows more efficient and diverse mechanisms of protein oxidation, folding, and quality control. The periplasm also contains structural elements and important environmental sensing modules, and it allows complex nanomachines to span the cell envelope. Recent work indicates that the size or intermembrane distance of the periplasm is controlled by periplasmic lipoproteins that anchor the outer membrane to the periplasmic peptidoglycan polymer. This periplasm intermembrane distance is critical for sensing outer membrane damage and dictates length of the flagellar periplasmic rotor, which controls motility. These exciting results resolve longstanding debates about whether the periplasmic distance has a biological function and raise the possibility that the mechanisms for maintenance of periplasmic size could be exploited for antibiotic development.

The usefulness of changing focus during examination using Gram staining as initial diagnostic clue for infective tuberculosis.

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Atsukawa, Yoshiko; Kawakami, Sayoko; Asahara, Miwa; Ishigaki, Shinobu; Tanaka, Takashi; Ono, Yasuo; Nishiya, Hajime; Fujisaki, Ryuichi; Koga, Ichiro; Ota, Yasuo; Miyazawa, Yukihisa

2011-08-01

Gram staining is a useful technique for detecting bacteria but is highly questionable in detecting Mycobacterium tuberculosis. Its detection generally requires special staining, such as Ziehl-Neelsen staining. We experienced three cases in which tuberculosis was first suggested by Gram staining of sputum or pus, confirmed by Ziehl-Neelsen staining, and diagnosed by polymerase chain reaction or culture. To find colorless tubercle bacilli in clinical samples with various organisms, varying the focus to slightly longer and shorter during study of the slides is indispensable. We present criteria for detecting infective pulmonary tuberculosis in Gram staining. First, in the ordinary focus, weakly stained, thin, gram-positive bacilli are found; second, with a slightly longer focus distance, the thin, cord-like, conspicuous gram-positive bacilli can be observed; and third, with a shorter focus distance, the gram-positive bacilli have changed into the brightened, colorless, or ghost ones. Four laboratory technologists each evaluated 20 Gram-stained samples after being lectured on the criteria, with no prior information about the sample. They accurately evaluated the presence of the bacilli in Gram-stained preparations in more than 90% of samples containing 3+ bacilli on Ziehl-Neelsen staining. Gram staining is available as an easy and rapid initial clue to recognize highly infective tuberculosis.

Central Venous Catheter-Related Bloodstream Infection with Kocuria kristinae in a Patient with Propionic Acidemia.

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Kimura, Masato; Kawai, Eichiro; Yaoita, Hisao; Ichinoi, Natsuko; Sakamoto, Osamu; Kure, Shigeo

2017-01-01

Kocuria kristinae is a catalase-positive, coagulase-negative, Gram-positive coccus found in the environment and in normal skin and mucosa in humans; however, it is rarely isolated from clinical specimens and is considered a nonpathogenic bacterium. We describe a case of catheter-related bacteremia due to K. kristinae in a young adult with propionic acidemia undergoing periodic hemodialysis. The patient had a central venous catheter implanted for total parenteral nutrition approximately 6 months prior to the onset of symptoms because of repeated acute pancreatitis. K. kristinae was isolated from two sets of blood cultures collected from the catheter. Vancomycin followed by cefazolin for 16 days and 5-day ethanol lock therapy successfully eradicated the K. kristinae bacteremia. Although human infections with this organism appear to be rare and are sometimes considered to result from contamination, physicians should not underestimate its significance when it is isolated in clinical specimens.

[i]Legionella spp[/i]., amoebae and not-fermenting Gram negative bacteria in an Italian university hospital water system

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Pasqualina Laganà

2014-09-01

Full Text Available [b]Introduction. [/b]In hospital and other health care facilities, contamination of water systems by potentially infectious microorganisms, such as bacteria, viruses and protozoa, is a source of nosocomial infections, which may originate fromcolonization of water pipes, cooling towers, spa pools, taps, showers and water supplies. [b]Objective. [/b]The study focuses on the occurrence of [i]Legionella spp.[/i], free-living amoebae and non-fermenting Gram-negative microorganisms in a University hospital water system located in the town of Messina (Sicily, Italy, which had never been examined previously. Materials and Methods. From January 2008 – March 2009, hot tap water samples were collected from 10 wards.[i] Legionella spp[/i]. recovered on selective culture medium were identified by microagglutination latex test; free-living amoebae were cultured using [i]Escherichia coli [/i]as a food source. Non-fermenting Gram negative microorganisms were identified by API 20 NE strips. [b]Results.[/b] [i]Legionella spp.[/i] were found in 33.33% of the samples. [i]L. pneumophila[/i] serogroup 1 was recovered from the Laboratory Diagnostic and Anaesthesia-Neurology Wards, with a peak of 3.5 × 10[sup]4[/sup] cfu/L in May 2008. [i]L. pneumophila[/i] serogroups 2–14 were found in the Othorhinolaryngology, Pathologic Anatomy, Paediatrics and Surgery Wards, and peaked (4 × 10[sup]4[/sup] cfu/L in April 2008. Pseudomonadaceae and Hyphomycetes were also detected. Legionella spp. were recovered from samples positive for non-pathogenic amoebae [i]Hartmannella spp[/i]. [b]Conclusion.[/b] This first study of a Messina hospital water system suggested potential health risks related to the detection of [i]Hartmannella spp[/i]., as reservoirs for[i] Legionella spp.[/i], and Pseudomonas aeruginosa, a Gram negative non-fermenting bacterium frequently causing nosocomial pneumonia. The urgent need for monitoring programmes and prevention measures to ensure hospital water

Methods for Confirming the Gram Reaction of Gram-variable Bacillus Species Isolated from Tobacco

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Morin A

2014-12-01

Full Text Available Bacillus is a predominant genus of bacteria isolated from tobacco. The Gram stain is the most commonly used and most important of all diagnostic staining techniques in microbiology. In order to help confirm the Gram positivity of Bacillus isolates from tobacco, three methods using the chemical differences of the cell wall and membrane of Gram-positive and Gram-negative bacteria were investigated: the KOH (potassium hydroxide, the LANA (L-alanine-4-nitroanilide, and the vancomycin susceptibility tests. When colonies of Gram-negative bacteria are treated with 3% KOH solution, a slimy suspension is produced, probably due to destruction of the cell wall and liberation of deoxyribonucleic acid (DNA. Gram-positive cell walls resist KOH treatment. The LANA test reveals the presence of a cell wall aminopeptidase that hydrolyzes the L-alanine-4-nitroanilide in Gram-negative bacteria. This enzyme is absent in Gram-positive bacteria. Vancomycin is a glycopeptide antibiotic inhibiting the cell wall peptido-glycan synthesis of Gram-positive microorganisms. Absence of lysis with KOH, absence of hydrolysis of LANA, and susceptibility to vancomycin were used with the Gram reaction to confirm the Gram positivity of various Bacillus species isolated from tobacco. B. laevolacticus excepted, all Bacillus species tested showed negative reactions to KOH and LANA tests, and all species were susceptible to vancomycin (5 and 30 µg.

In vitro activity of tigecycline and comparator agents against a global collection of Gram-negative and Gram-positive organisms: tigecycline Evaluation and Surveillance Trial 2004 to 2007.

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Garrison, Mark W; Mutters, Reinier; Dowzicky, Michael J

2009-11-01

The Tigecycline Evaluation and Surveillance Trial began in 2004 to monitor the in vitro activity of tigecycline and comparator agents against a global collection of Gram-negative and Gram-positive pathogens. Against Gram negatives (n = 63 699), tigecycline MIC(90)'s ranged from 0.25 to 2 mg/L for Escherichia coli, Haemophilus influenzae, Acinetobacter baumannii, Klebsiella oxytoca, Enterobacter cloacae, Klebsiella pneumoniae, and Serratia marcescens (but was > or =32 for Pseudomonas aeruginosa). Against Gram-positive organisms (n = 32 218), tigecycline MIC(90)'s were between 0.06 and 0.25 mg/L for Streptococcus pneumoniae, Enterococcus faecium, Streptococcus agalactiae, Staphylococcus aureus, and Enterococcus faecalis. The in vitro activity of tigecycline was maintained against resistant phenotypes, including multidrug-resistant A. baumannii (9.2% of isolates), extended-spectrum beta-lactamase-producing E. coli (7.0%) and K. pneumoniae (14.0%), beta-lactamase-producing H. influenzae (22.2%), methicillin-resistant S. aureus (44.5%), vancomycin-resistant E. faecium (45.9%) and E. faecalis (2.8%), and penicillin-resistant S. pneumoniae (13.8%). Tigecycline represents a welcome addition to the armamentarium against difficult to treat organisms.

Detection of Extended Spectrum Beta-Lactamases Among Gram Negative Bacilli Recovered from Cattle Feces In Benin City, Nigeria

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Helen Oroboghae OGEFERE

2017-06-01

Full Text Available This study was carried out to determine the prevalence of extended spectrum beta-lactamase (ESBL among Gram negative bacteria isolated from cattle feces in Benin City, Nigeria. A total of 250 Gram negative bacteria isolates were recovered from cattle feces and were processed microbiologically using standard techniques. Emergent colonies were identified and antibacterial susceptibility tests were determined using Kirby-Bauer disk diffusion method. All bacterial isolates were screened for the presence of ESBL using the double-disc synergy method. A total of 37 (14.8% isolates were positive for ESBL, with 33 (13.2% indicated by ceftazidime, while only 4 (1.6% were indicated by both ceftazidime and cefotaxime (P < 0.0001. Of the Gram negative bacterial isolates recovered, Salmonella species was the most prevalent ESBL-producer with 55.0% prevalence (P = 0.0092, while no isolate of Pseudomonas aeruginosa produced ESBL. ESBL-positive isolates showed poor susceptibility to the tested antibacterial agents in comparison with non-ESBL-producers and imipenem was the most active antibiotic. The prevalence of ESBL among Gram negative bacilli recovered from cattle feces was 14.8%. The study advises prudent use of antibiotics in the treatment of cattle and harps on improved hygiene in managing cattle, as they are potential reservoirs of ESBL-producing organisms.