... is in a class of medications called carbapenem antibiotics. It works by killing bacteria.Antibiotics such as aztreonam injection will not work for colds, flu, or other viral infections. Taking ...
Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny
To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to
Kurishita, A.; Ono, T. (Tohoku Univ., Sendai (Japan). School of Medicine); Uchida, A. (Kyoto Univ. (Japan). Radiation Biology Center)
The effects of combined treatment with OK-432, an immunomodulator prepared from Streptococcus haemolyticus, and aztreonam, a monobactum antibiotic, in the prevention of radiation-induced bacteraemia and mortality were examined in ICR-MCH mice irradiated with 9.5 Gy. The organisms recovered from the irradiated mice were Streptococcus faecalis and Proteus mirabilis. Treatment with aztreonam reduced the incidence of mice infected with Proteus mirabilis (p<0.01), but it showed no efficacy on Streptococcus faecalis. OK-432 could reduce the frequency of bacteraemia attributed to both organisms (p<0.05). Combined treatment with OK-432 and aztreonam further decreased the incidence of bacteraemia by both organisms; no organisms were recovered at 14 days following irradiation. The survival rate at 30 days following irradiation was 80% in mice treated with OK-432 plus aztreonam and 55% with OK-432 alone, while it was 0% in the groups treated with aztreonam or saline alone. These results indicated that combined treatment with OK-432 and a suitable antibiotic such as aztreonam is more effective than OK-432 or aztreonam alone. (Author).
Kurishita, A.; Ono, T.; Uchida, A.
The effects of combined treatment with OK-432, an immunomodulator prepared from Streptococcus haemolyticus, and aztreonam, a monobactum antibiotic, in the prevention of radiation-induced bacteraemia and mortality were examined in ICR-MCH mice irradiated with 9.5 Gy. The organisms recovered from the irradiated mice were Streptococcus faecalis and Proteus mirabilis. Treatment with aztreonam reduced the incidence of mice infected with Proteus mirabilis (p<0.01), but it showed no efficacy on Streptococcus faecalis. OK-432 could reduce the frequency of bacteraemia attributed to both organisms (p<0.05). Combined treatment with OK-432 and aztreonam further decreased the incidence of bacteraemia by both organisms; no organisms were recovered at 14 days following irradiation. The survival rate at 30 days following irradiation was 80% in mice treated with OK-432 plus aztreonam and 55% with OK-432 alone, while it was 0% in the groups treated with aztreonam or saline alone. These results indicated that combined treatment with OK-432 and a suitable antibiotic such as aztreonam is more effective than OK-432 or aztreonam alone. (Author)
Duma, R J; Berry, A J; Smith, S M; Baggett, J W; Swabb, E A; Platt, T B
Aztreonam was administered as a single, 2-g intravenous dose to 25 patients with noninflamed meninges and to 9 patients with inflamed meninges. It was well tolerated and was detected in the cerebrospinal fluid at the initial sampling period at 1 h after the end of infusion. Aztreonam levels in the cerebrospinal fluid of patients with inflamed meninges were four times higher than those recorded for the same time period in patients with noninflamed meninges. Aztreonam concentrations in cerebrospinal fluid in the presence of normal and inflamed meninges exceeded the inhibitory and bactericidal concentrations for most gram-negative bacteria. Thus, a multiple-dose treatment regimen with 2-g intravenous doses every 6 h appears to be appropriate for clinical trials of aztreonam for the treatment of gram-negative bacillary meningitis which is caused by susceptible organisms. PMID:6542765
Karlowsky, James A; Kazmierczak, Krystyna M; de Jonge, Boudewijn L M; Hackel, Meredith A; Sahm, Daniel F; Bradford, Patricia A
The combination of the monobactam aztreonam and the non-β-lactam β-lactamase inhibitor avibactam is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing Enterobacteriaceae , a difficult-to-treat subtype of carbapenem-resistant Enterobacteriaceae for which therapeutic options are currently very limited. The present study tested clinically significant isolates of Enterobacteriaceae ( n = 51,352) and Pseudomonas aeruginosa ( n = 11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for in vitro susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using a standard broth microdilution methodology. Avibactam was tested at a fixed concentration of 4 μg/ml in combination with 2-fold dilutions of aztreonam. The MIC 90 s of aztreonam-avibactam and aztreonam were 0.12 and 64 μg/ml, respectively, for all Enterobacteriaceae isolates; >99.9% of all isolates and 99.8% of meropenem-nonsusceptible isolates ( n = 1,498) were inhibited by aztreonam-avibactam at a concentration of ≤8 μg/ml. PCR and DNA sequencing identified 267 Enterobacteriaceae isolates positive for MBL genes (NDM, VIM, IMP); all Enterobacteriaceae carrying MBLs demonstrated aztreonam-avibactam MICs of ≤8 μg/ml and a MIC 90 of 1 μg/ml. Against all P. aeruginosa isolates tested, the MIC 90 of both aztreonam-avibactam and aztreonam was 32 μg/ml; against MBL-positive P. aeruginosa isolates ( n = 452), MIC 90 values for aztreonam-avibactam and aztreonam were 32 and 64 μg/ml, respectively. The current study demonstrated that aztreonam-avibactam possesses potent in vitro activity against a recent, sizeable global collection of Enterobacteriaceae clinical isolates, including isolates that were meropenem nonsusceptible, and against MBL-positive isolates of Enterobacteriaceae , for which there are few treatment options. Copyright © 2017 American
Mangioni, C; Bianchi, L; Bolis, P F; Lomeo, A M; Mazzeo, F; Ventriglia, L; Scalambrino, S
A prospective, randomized, multicenter study was conducted on the efficacy and safety of two prophylactic antibiotic regimens in both abdominal and vaginal hysterectomy. Patients received three intravenous doses of clindamycin (900 mg) plus either aztreonam (1 g) or cefotaxime (1 g); the doses were given at the induction of anesthesia and 8 and 16 hours later. A total of 170 patients undergoing abdominal hysterectomy and 142 patients undergoing vaginal hysterectomy completed the trial and were evaluated. Following abdominal hysterectomy infections occurred at the operative site in 1.2% of patients given a regimen including aztreonam and in 4.7% of those given a regimen including cefotaxime; the difference between the two groups was not significant. Neither were significant differences observed in the incidence of fever, the incidence of bacteriuria, the need for postoperative antibiotics, or the duration of postoperative hospitalization, although results were slightly better for patients receiving clindamycin plus aztreonam. Following vaginal hysterectomy, slightly but not significantly better results for the same parameters were obtained in the group given clindamycin plus cefotaxime. Diarrhea was the only adverse reaction attributable to antibiotic treatment and occurred more frequently in patients given cefotaxime. It was concluded that the two regimens were similarly effective and safe in preventing infections following hysterectomy.
Retsch-Bogart, George Z.; Quittner, Alexandra L.; Gibson, Ronald L.; Oermann, Christopher M.; McCoy, Karen S.; Montgomery, A. Bruce; Cooper, Peter J.
Background: We assessed the short-term efficacy and safety of aztreonam lysine for inhalation (AZLI [an aerosolized monobactam antibiotic]) in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) airway infection. Methods: In this randomized, double-blind, placebo-controlled, international study (AIR-CF1 trial; June 2005 to April 2007), patients (n = 164; ≥ 6 years of age) with FEV1 ≥ 25% and ≤ 75% predicted values, and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI (three times daily for 28 days) or placebo (1:1 randomization), then were monitored for 14 days after study drug completion. The primary efficacy end point was change in patient-reported respiratory symptoms (CF-Questionnaire-Revised [CFQ-R] Respiratory Scale). Secondary end points included changes in pulmonary function (FEV1), sputum PA density, and nonrespiratory CFQ-R scales. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. Results: After 28 days of treatment, AZLI improved the mean CFQ-R respiratory score (9.7 points; p < 0.001), FEV1 (10.3% predicted; p < 0.001), and sputum PA density (− 1.453 log10 cfu/g; p < 0.001), compared with placebo. Significant improvements in Eating, Emotional Functioning, Health Perceptions, Physical Functioning, Role Limitation/School Performance, and Vitality CFQ-R scales were observed. Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of “productive cough” was reduced by half in AZLI-treated patients. PA aztreonam susceptibility at baseline and end of therapy were similar. Conclusions: In patients with CF, PA airway infection, moderate-to-severe lung disease, and no recent use of antipseudomonal antibiotics or azithromycin, 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function, and was well tolerated. Trial registration: Clinicaltrials
Full Text Available There are not many articles about the chronic bronchial infection/colonization in patients with underlying lung disease other than cystic fibrosis (CF, especially with non-CF bronchiectasis (NCFBQ. The prevalence of B. cepacia complex is not well known in NCFBQ. The vast majority of published clinical data on Burkholderia infection in individuals with CF is comprised of uncontrolled, anecdotal, and/or single center experiences, and no consensus has emerged regarding treatment. We present two cases diagnosed with bronchiectasis (BQ of different etiology, with early pulmonary infection by B. cepacia complex, which was eradicated with inhaled aztreonam lysine.
Hansen, Christine; Skov, Marianne
and the clinical outcome of this infection; this article focuses on the use of inhaled antibiotics in chronic P. aeruginosa infection in CF, and specifically on studies including the use of inhaled aztreonam lysine in P. aeruginosa infection. Studies were identified using PubMed and ClinicalTrials.gov, searching...
Pitondo-Silva, André; Martins, Vinicius Vicente; Fernandes, Ana Flavia Tonelli; Stehling, Eliana Guedes
Pseudomonas aeruginosa can be found in water, soil, plants and, human and animal fecal samples. It is an important nosocomial pathogenic agent characterized by an intrinsic resistance to multiple antimicrobial agents and the ability to develop high-level (acquired) multidrug resistance through some mechanisms, among them, by the acquisition of plasmids and integrons, which are mobile genetic elements. In this study, 40 isolates from Brazilian soil were analyzed for antibiotic resistance, presence of integrons and plasmidial profile. The results demonstrated that the vast majority of the isolates have shown resistance for aztreonam (92.5%, n=37) and ticarcillin (85%, n=34), four isolates presented plasmids and eight isolates possess the class 1 integron. These results demonstrated that environmental isolates of P. aeruginosa possess surprising antibiotic resistance profile to aztreonam and ticarcillin, two antimicrobial agents for clinical treatment of cystic fibrosis patients and other infections occurred by P. aeruginosa. Copyright © 2014 Elsevier B.V. All rights reserved.
Combination of hypothiocyanite and lactoferrin (ALX-109) enhances the ability of tobramycin and aztreonam to eliminate Pseudomonas aeruginosa biofilms growing on cystic fibrosis airway epithelial cells.
Moreau-Marquis, Sophie; Coutermarsh, Bonita; Stanton, Bruce A
Chelating iron may be a promising new therapy to eliminate Pseudomonas aeruginosa biofilms in the lungs of cystic fibrosis (CF) patients. Here, we investigate whether ALX-109 [a defined combination of an investigational drug containing lactoferrin (an iron-binding glycoprotein) and hypothiocyanite (a bactericidal agent)], alone and in combination with tobramycin or aztreonam, reduces P. aeruginosa biofilms grown on human CF airway epithelial cells. P. aeruginosa (PAO1 and six clinical isolates of Pseudomonas) biofilms grown at the apical surface of confluent monolayers of CF airway epithelial cells were treated with ALX-109, either alone or in combination with tobramycin or aztreonam. Bacterial cfu remaining after treatment were determined by plate counting. ALX-109 alone reduced PAO1 biofilm formation, but had no effect on established biofilms. ALX-109 enhanced the ability of tobramycin and aztreonam to inhibit PAO1 biofilm formation and to reduce established PAO1 biofilms. ALX-109 and tobramycin were additive in disrupting established biofilms formed by six clinical isolates of P. aeruginosa obtained from the sputum of CF patients. Mucoid P. aeruginosa isolates were most susceptible to the combination of ALX-109 and tobramycin. In addition, ALX-109 also enhanced the ability of aztreonam to reduce established PAO1 biofilms. Inhalation therapy combining hypothiocyanite and lactoferrin with TOBI(®) (tobramycin) or Cayston(®) (aztreonam) may be beneficial to CF patients by decreasing the airway bacterial burden of P. aeruginosa. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Marshall, Steven; Hujer, Andrea M; Rojas, Laura J; Papp-Wallace, Krisztina M; Humphries, Romney M; Spellberg, Brad; Hujer, Kristine M; Marshall, Emma K; Rudin, Susan D; Perez, Federico; Wilson, Brigid M; Wasserman, Ronald B; Chikowski, Linda; Paterson, David L; Vila, Alejandro J; van Duin, David; Kreiswirth, Barry N; Chambers, Henry F; Fowler, Vance G; Jacobs, Michael R; Pulse, Mark E; Weiss, William J; Bonomo, Robert A
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included bla IMP , bla NDM , bla OXA-48 , bla CTX-M , bla AmpC , and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log 10 -CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log 10 -CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae . Copyright © 2017 American Society for Microbiology.
ERJAVEC, Z; DEVRIESHOSPERS, HG; VANKAMP, H; VANDERWAAIJ, D; HALIE, MR; DAENEN, SMGJ
143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxim (T/C). Response after 72 h was significantly better in patients receiving Imi
Pseudomonas aeruginosa was less susceptible to cefotaxime (2%) and aztreonam (33%), and highly susceptible to ceftazidime (72%) whereas Acinetobacter baumannii was highly resistant to aztreonam (100%), to cefotaxime (96%) and cetazidime (62%). Imipenem (98%) was the most active antibiotic followed by the ...
Westh, H; Frimodt-Møller, N; Gutschik, E
Nine Haemophilus species strains, all beta-lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments. Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone. Synergism between beta...
In this study we assessed the functionality of integrons, melanin-like pigment and biofilm formation on multidrug resistance among environmental isolates of Stenotrophomonas maltophilia. Marked resistances were noted against aztreonam (60%), cefepime (68%), ceftazidime (77%), ciprofloxacin (72%), gentamicin (65%), ...
In this study the antibiotic susceptibility of 51 P. aeruginosa strains isolated from clinical samples were detected by the disc diffusion test. The susceptibility of P. aeruginosa strains were found as respectively 55% amicacin, 43% aztreonam, 75% netilmycin, 68% sefepim, 73% ceftazidim, 76% ciproflaxacin, 37% gentamicin, ...
Fjaellegaard, Katrine; Sin, Melda Dönmez; Browatzki, Andrea
To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled......, exacerbations and QoL, whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest, including exacerbation rate. Adverse events, including bronchospasm, have been reported in association with tobramycin and aztreonam. Several antibiotic treatment regimens have been...... shown to improve QoL and exacerbation rate, whereas findings regarding sputum production, lung function and admissions have been conflicting. Evidence-based treatment algorithms for antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies....
Kurishita, A.; Ono, T.
Radiation induced hematopoietic and gastro-intestinal damages in mice were tried to alleviate experimentally by post-treatment. Combined treatment of OK-432 and aztreonam clearly prevented the radiation induced sepsis and elevated the survival rate in mice; the survival was 80% in the OK-432 plus aztreonam group while it was 55% in the group treated with OK-432 alone and 0% with saline. Irsogladine maleate, an anti-ulcer drug, increased the survival rate of jejunal crypt stem cells with a clear dose-related trend. The D 0 for irsogladine maleate was 2.8 Gy although it was 2.3 Gy for saline, These findings suggest that some conventional drugs are effective for radiation induced hematopoietic and gastro-intestinal damages and the possibility that they can be applied for people exposed to radiation accidentally. (author)
Dias, Rubens Clayton da Silva; Borges-Neto, Armando Alves; Ferraiuoli, Giovanna Ianini D’Almeida; de-Oliveira, Márcia P.; Riley, Lee W.; Moreira, Beatriz Meurer
Production of extended-spectrum β-lactamases (ESBL) has been reported in virtually all species of Enterobacteriaceae, which greatly complicates the therapy of infections caused by these organisms. However, the frequency of isolates producing AmpC β-lactamases, especially plasmid mediated AmpC (pAmpC), is largely unknown. These β-lactamases confer resistance to extended spectrum cephalosporins and aztreonam, a multidrug-resistant (MDR) profile. The aim of the present study was to determine the...
Moriyama, Brad; Henning, Stacey A; Childs, Richard; Holland, Steven M; Anderson, Victoria L; Morris, John C; Wilson, Wyndham H; Drusano, George L; Walsh, Thomas J
To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.
Dixon, Nyssa; Fowler, Randal C; Yoshizumi, A; Horiyama, Tsukasa; Ishii, Y; Harrison, Lucas; Geyer, Chelsie N; Moland, Ellen Smith; Thomson, Kenneth; Hanson, Nancy D
A novel metallo-β-lactamase gene, blaIMP-27, was identified in unrelated Proteus mirabilis isolates from two geographically distinct locations in the United States. Both isolates harbor blaIMP-27 as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27. Copyright © 2016 Dixon et al.
Objective: To determine the in vitrodisk diffusion and MIC patterns of the therapeutic alternatives for Salmonella Typhi. Study Design: Across-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from June 2011 to May 2013. Methodology: Clinical samples were collected from suspected cases of Salmonella infections. Culture was obtained on standard media. Suspected Salmonella colonies were tested by API 20E and confirmed by serology. The isolates were tested for resistance to various antibiotics by Kirby-Bauer disc diffusion method. MIC was done on MDR and ciprofloxacin intermediate or resistant cases by E-strips for selected antibiotics. Results: One hundred and twenty-eight isolates of Salmonella Typhi were recovered from 2230 specimens. Resistance by disk diffusion technique was 72% for ampicillin, 41.2% for cotrimoxazole, 38% for chloramphenicol, 8% for ciprofloxacin, 4.7% for cefpodoxime, 3.5% each for ertapenem aztreonam and moxifloxacin 2.4% for ceftriaxone and 2.3% for doripenem. No resistance was noted for imipenem, cefepime and gatifloxacin. Imipenem MIC90 was 0.38 and MIC50 was 0.25. For cefpirome, MIC90 was 0.64 and MIC50 was 0.09. For aztreonam, MIC90 was 0.12 and MIC50 was 0.09. For cefpodoxime MIC90 was 0.75 and MIC50 was 0.38. For azithromycin, these values were 16.0 and 7.0; and for tigecycline they were 0.25 and 0.09. Conclusion: Imipenem, azithromycin, tigecycline, aztreonam, cefpodoxime and cefpirome are potential therapeutic agents for resistant Salmonella Typhi infection. (author)
Full Text Available The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound—ethyl 2-(1-acetylpiperidine-4-carboxamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate—was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.
Sato, Kazuki; Ushioda, Kenichi; Akiba, Keiji; Matsumoto, Yoshimi; Maseda, Hideaki; Ando, Tasuke; Isogai, Emiko; Nakae, Taiji; Yoneyama, Hiroshi
The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound-ethyl 2-(1-acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate-was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.
Hiraoka, M; Okamoto, R; Inoue, M; Mitsuhashi, S
Four types of beta-lactamases consisting of a penicillinase type I (TEM-1), a penicillinase type II (OXA-1), a cephalosporinase of Citrobacter freundii, and a cephalosporinase of Proteus vulgaris were introduced into Escherichia coli MC4100 and its omp mutants, MH1160 (MC4100 ompR1) and MH760 (MC4100 ompR2), by transformation. Effects of the combination of the omp mutations and these beta-lactamases on the susceptibility of E. coli strains were studied with 15 beta-lactam antibiotics including cephalosporins, cephamycins, penicillins, imipenem, and aztreonam. The ompR1 mutant, MH1160, lacks OmpF and OmpC, and it showed reduced susceptibility to 11 of the 15 beta-lactam agents. The reduction in susceptibility to cefoxitin, moxalactam, and flomoxef was much greater than reduction in susceptibility to the other agents. When the ompR1 mutant produced the cephalosporinase of C. freundii, the susceptibility of the mutant to 12 of the 15 beta-lactam antibiotics decreased. The reduction in susceptibility of MH1160 to 10 of the 12 agents affected by the enzyme was two- to fourfold greater than that observed in MC4100. Such a synergistic effect was also observed with the cephalosporinase of P. vulgaris and ompR1 mutation against six cephalosporins, moxalactam, and aztreonam. Images PMID:2658786
Poon, Henry; Chang, Mei H; Fung, Horatio B
Ceftaroline is a cephalosporin with expanded gram-positive activity recently approved for clinical uses by the US Food and Drug Administration. This article provides an overview of the in vitro and in vivo activities, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of ceftaroline. Relevant information was identified through a search of PubMed (1990-April 2011), EMBASE (1990-April 2011), International Pharmaceutical Abstracts (1970-April 2011), and Google Scholar using the key words ceftaroline, PPI-0903, PPI-0903M, T-91825, and TAK-599. A review of the reference lists of identified articles, a search of the US Food and Drug Administration Web site, and posters and abstracts from scientific meetings yielded additional publications. In vitro, ceftaroline exhibits activity against most aerobic gram-positive isolates, common aerobic gram-negative respiratory pathogens, and some gram-positive anaerobes. The MIC range for most Staphylococcus aureus isolates, including vancomycin-resistant strains was between ≤0.008 and 4 μg/mL. In Phase III studies (CANVAS 1 and CANVAS 2), ceftaroline was found to be noninferior to vancomycin + aztreonam for the treatment of complicated skin and skin-structure infections, with a clinical cure rate of 91.6% among clinically evaluable patients (ceftaroline versus vancomycin + aztreonam: difference, -1.1; 95% CI, -4.2 to 2.0; P = NS). Ceftaroline's efficacy has also been assessed for the treatment of community-acquired pneumonia in 2 Phase III studies (FOCUS 1 and FOCUS 2) and was equivalent to ceftriaxone, with cure rates of 84.3% and 77.7%, respectively, among clinically evaluable patients in the combined analysis (ceftaroline versus ceftriaxone: difference, 6.7; 95% CI, 1.6 to 11.8). The recommended dosage for patients 18 years and older is 600 mg IV every 12 hours. Dosage adjustment is necessary in patients with renal impairment (creatinine clearance ≤50 mL/min). The
Mojdeh Hakemi Vala
Full Text Available Please cite this article as: Hakemi Vala M, Hallajzadeh M, Fallah F, Hashemi A, Goudarzi H. Characterization of the extended-spectrum beta-lactamase producers among non-fermenting gram-negative bacteria isolated from burnt patients. Arch Hyg Sci 2013;2(1:1-6. Background & Aims of the Study: Extended-spectrum beta-Lactamases (ESBLs represent a major group of beta-lactamases which are responsible for resistance to oxyimino-cephalosporins and aztreonam and currently being identified in large numbers throughout the world. The objective of this study was to characterize ESBL producers among non-fermenter gram-negative bacteria isolated from burnt patients. Materials & Methods: During April to July 2012, 75 non-fermenter gram-negative bacilli were isolated from 240 bacterial cultures collected from wounds of burnt patients admitted to the Burn Unit at Shahid Motahari Hospital (Tehran, Iran. Bacterial isolation and identification was done using standard methods. Antimicrobial susceptibility testing was performed by disk diffusion method for all strains against selected antibiotics and minimum inhibitory concentration was determined by microdilution test. The ability to produce ESBL was detected through double disk synergy test among candidate strains. Results: Of 75 non-fermenter isolates, 47 Pseudomonas aeruginosa and 28 Acinetobacter baumannii were identified. The resistance of P. aeruginosa isolates to tested antibiotics in antibiogram test were 100% to cefpodoxime, 82.98% to ceftriaxone, 78.73% to imipenem, 75% to meropenem, 72.72% to gentamicin, 69.23% to ciprofloxacin and aztreonam, 67.57% to cefepime, 65.95% to ceftazidime, and 61.53% to piperacillin. The results for Acinetobacter baumannii were 100% to ceftazidime, cefepime, ciprofloxacin, imipenem, meropenem, cefpodoxime, and cefotaxim, 96.85% to gentamicin, 89.65% to ceftriaxone, 65.51% to aztreonam, and 40% to piperacillin. Double disk synergy test showed that 21 (28% of non
Tada, Tatsuya; Shrestha, Shovita; Shimada, Kayo; Ohara, Hiroshi; Sherchand, Jeevan B; Pokhrel, Bharat M; Kirikae, Teruo
A novel PER-type extended-spectrum β-lactamase, PER-8, was identified in an Acinetobacter baumannii clinical isolate obtained in Nepal. The amino acid sequence of PER-8 has a substitution at position 39 (Gly to Glu) compared with that of PER-7. The k cat / K m ratio of PER-8 for aztreonam was lower than that of PER-7, while the k cat / K m ratio of PER-8 for imipenem was higher than that of PER-7. The genomic environment surrounding bla PER-8 was intI1 bla PSE-1 qacEDI sulI IS CR1-bla PER-8 gts sulI orfX on a 100-kb plasmid. Copyright © 2017 American Society for Microbiology.
Potter, Robert F; D'Souza, Alaric W; Dantas, Gautam
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Wuthiekanun, Vanaporn; Amornchai, Premjit; Langla, Sayan; White, Nicholas J; Day, Nicholas P J; Limmathurotsakul, Direk; Peacock, Sharon J
Leptospira Vanaporn Wuthiekanun (LVW) agar was used to develop a disk diffusion assay for Leptospira spp. Ten pathogenic Leptospira isolates were tested, all of which were susceptible to 17 antimicrobial agents (amoxicillin/clavulanic acid, amoxicillin, azithromycin, cefoxitin, ceftazidime, ceftriaxone, chloramphenicol, ciprofloxacin, clindamycin, doripenem, doxycycline, gentamicin, linezolid, nitrofurantoin, penicillin, piperacillin/tazobactam, and tetracycline). All 10 isolates had no zone of growth inhibition for four antimicrobials (fosfomycin, nalidixic acid, rifampicin, and trimethoprim/sulfamethoxazole). Of the ten Leptospira, seven had a growth inhibition zone of ≤ 21 mm for aztreonam, the zone diameter susceptibility break point for Enterobacteriaceae. This assay could find utility as a simple screening method during the epidemiological surveillance of antimicrobial resistance in Leptospira spp. © The American Society of Tropical Medicine and Hygiene.
Flávia L. P. C. Pellegrino
Full Text Available Previous analysis of Pseudomonas aeruginosa class-1 integrons from Rio de Janeiro, Brazil, revealed the blaGES gene in one isolate. We screened isolates of two widespread PFGE genotypes, A and B, at a public hospital in Rio, for the presence of blaGES. The gene was detected in all seven P. aeruginosa isolates belonging to genotype B. Three of the seven genotype-B isolates were resistant to amikacin, aztreonam, ceftazidime, cefepime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin-tazobactam and ticarcillin-clavulanic acid. The other four isolates were resistant to all these agents, except gentamicin, imipenem, meropenem and piperacillin-tazobactam. A synergistic effect between ceftazidime and imipenem or clavulanic acid suggested the production of GES-type ESBL.
Potter, Robert F.; D’Souza, Alaric W.; Dantas, Gautam
Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments. PMID:27912842
N. I. Gabrielan
Full Text Available Antibiotic and fagosensitivity most etiologically important nosocomial strains of bacteria – Pseudomonas aeru- ginosa, Klebsiella pneumoniae, E. coli, Proteus spp., Staphylococcus spp. were studied. Multiple drug-resistant bacteria as gram-positive and gram-negative, isolated from 8 substrates, had been demonstrated. With regard to the sensitivity of Pseudomonas aeruginosa >40% was observed in 40–50% of the strains to aminoglycosides – aztreonam, amikacin, netilmicin, and only 23–25% of the strains – to gentamicin and levofloxacin (an average of antibiotic susceptibility was 27%. All strains of ESBL Klebsiella drew up and were sensitive only to imipenem, meropenem and aminoglycosides. Specific phages lysed 43–48% of the strains Pseudomonas aeruginosa and Klebsiella pneumoniae, E. coli, Pro- teus spp., multidrug resistant strains of Staphylococcus spp. It is proposed to introduce the use of phages in clinical practice.
Margate, Emmily; Magalhães, Vera; Fehlberg, Lorena Cristina Corrêa; Gales, Ana Cristina; Lopes, Ana Catarina Souza
In this brief communication we describe the occurrence of a KPC-producing Serratia marcescens isolate in a home-care patient from Recife, Brazil. The blaKPC, blaSPM, blaIMP, blaVIM, blaOXA, blaCTX-M, blaSHV, blaTEM and blaGES genes were investigated by Polymerase Chain Reaction (PCR) and DNA sequencing. The isolate was positive for blaKPC-2 and blaTEM-1 and was resistant to aztreonam, cefepime, cefotaxime, imipenem, meropenem, gentamicin, ciprofloxacin and cefazidime, and susceptible only to amikacin, tigecycline and gatifloxacin. This is the first report in Brazil of KPC-producing S. marcescens clinical isolate outside of a hospital environment. Caregivers should be alert for the presence of this isolate in the community setting.
Ciofu, Oana; Jensen, Tim; Pressler, Tacjana
in pulmonary function (as a percentage of the predictive values) was 5.6% for FEV1 (forced expiratory volume in the first second) and 8.6% for FVC (forced vital capacity). C-reactive protein and erythrocyte sedimentation rate (ESR) and leukocyte count decreased significantly. In courses administered...... for chronic infection with B. cepacia the post treatment FEV1 and FVC values were higher than the pre-treatment values, and all the inflammatory parameters decreased. The geometric means of minimal inhibitory concentration (MICs) (microg/mL) for P. aeruginosa (B. cepacia) were: tobramycin 6 (59......), ciprofloxacin 1.2 (9.7), piperacillin 49 (16.3), ceftazidime 26 (23), aztreonam 26 (35), imipenem 6.4 (not determined) and meropenem 5.1 (4.8). No statistically significant increase in the MICs of meropenem for either pathogen occurred during therapy. Of the 124 courses, 115 were tolerated without any clinical...
Agersø, Yvonne; Hasman, Henrik; Cavaco, Lina M.
Methicillin-resistant Staphylococcus aureus (MRSA), especially CC398, have emerged in livestock worldwide. We investigated the occurrence of MRSA in pigs at slaughter and in retail meat. During 2009, nasal swabs (n=789) were taken from pigs at slaughter. Moreover, 866 meat samples [Danish: pork...... (153), broiler meat (121), beef (142) and; imported: pork (173), broiler meat (193), and beef (84)] were randomly collected in retail stores and outlets. MRSA was isolated from nasal swabs or from meat samples after preenrichment (Mueller Hinton broth with 6.5% NaCl), selective enrichment (tryptone...... soya broth with 4mg/L cefoxitine and 75mg/L aztreonam) and selective plating on Brilliance Chromogenic MRSA agar. The presence of mecA was confirmed by PCR and the MRSA isolates were spa typed. Novel MRSA spa types were characterized by MLST, PFGE and SCCmec typing. Thirteen percent (101...
Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L
In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Wang, Fu-Der; Lin, Mei-Lin; Lee, Wen-Sen; Liu, Cheng-Yi
The resistance rates of ampicillin/sulbactam 2:1 against imipenem-susceptible and -resistant Acinetobacter baumannii were 23.5 and 30%, respectively. Ceftazidime/sulbactam combination showed significant reduction of resistant rates against Enterobacter cloacae, A. baumannii, ESBL Klebsiella pneumoniae. MIC90 of cefoperazone against E. cloacae, Serratia marcescens, A. baumannii and ESBL K. pneumoniae were > 128 mg/l. Addition of sulbactam enhanced the antimicrobial activities significantly. When imipenem was combined with sulbactam, the resistant rates against imipenem-resistant A. baumanni were significantly reduced. Cefepime/sulbactam combination was active against imipenem-resistant A. baumanni. The resistance rates of aztreonam/sulbactam combination against E. cloacae, imipenem-sensitive and resistant A. baumannii, ESBL K. pneumoniae were lowered significantly. The cefotaxime/sulbactam combination showed a significant improvement of activities against E. cloacae, S. marcescens, A. baumannii and ESBL K. pneumoniae. Copyright 2004 Elsevier B.V.
Bahar, G; Eraç, B; Mert, A; Gülay, Z
A Providencia rettgeri strain resistant to extended-spectrum cephalosporins and intermediate to aztreonam was isolated from the urine of a patient hospitalized in the urology clinic of SSK Educational Hospital in Ankara. Clavulanic acid restored the activity of extended-spectrum cephalosporins, suggesting that the strain was harboring an extended-spectrum beta-lactamase. Since the PER-1 enzyme is widespread in Turkey, and had been already detected in a related species such as Proteus mirabilis, the Providencia strain was suspected of harboring a PER-1 enzyme, which was indeed detected by PCR. This is the first description in a P. rettgeri isolate of a PER-1 enzyme which is widespread among Acinetobacter baumanni and Pseudomonas aeruginosa strains in Turkey.
Sougakoff, W; Naas, T; Nordmann, P; Collatz, E; Jarlier, V
The role of the serine residue found at position 237 in the carbapenemase Sme-1 has been investigated by constructing a mutant in which Ser-237 was replaced by an alanine. The S237A mutant showed a catalytic behavior against penicillins and aztreonam very similar to that of Sme-1. By contrast, S237A was characterized by a reduced catalytic efficiency against cephems, such as cephalothin and cephaloridine. In addition, the weak activity of Sme-1 against the cephamycin cefoxitin was hardly detectable with the mutant enzyme. Finally, the Ser-237-->Ala mutation resulted in a marked decrease in catalytic activity against imipenem, showing that Ser-237 contributes to the carbapenemase activity of the class A beta-lactamase Sme-1.
Full Text Available Abstract Background In a recent multi-centre Italian survey (2003–2004, conducted in 45 laboratories throughout Italy with the aim of monitoring microorganisms responsible for severe infections and their antibiotic resistance, Acinetobacter baumannii was isolated from various wards of 9 hospitals as one of the most frequent pathogens. One hundred and seven clinically significant strains of A. baumannii isolates were included in this study to determine the in vitro activity of tigecycline and comparator agents. Methods Tests for the susceptibility to antibiotics were performed by the broth microdilution method as recommended by CLSI guidelines. The following antibiotics were tested: aztreonam, piperacillin/tazobactam, ampicillin/sulbactam, ceftazidime, cefepime, imipenem, meropenem tetracycline, doxycycline, tigecycline, gentamicin, amikacin, ciprofloxacin, colistin, and trimethoprim/sulphametoxazole. The PCR assay was used to determine the presence of OXA, VIM, or IMP genes in the carbapenem resistant strains. Results A. baumannii showed widespread resistance to ceftazidime, ciprofloxacin and aztreonam in more than 90% of the strains; resistance to imipenem and meropenem was 50 and 59% respectively, amikacin and gentamicin were both active against about 30% of the strains and colistin about 99%, with only one strain resistant. By comparison with tetracyclines, tigecycline and doxycycline showed a higher activity. In particular, tigecycline showed a MIC90 value of 2 mg/L and our strains displayed a unimodal distribution of susceptibility being indistinctly active against carbapenem-susceptible and resistant strains, these latter possessed OXA-type variant enzymes. Conclusion In conclusion, tigecycline had a good activity against the MDR A. baumannii strains while maintaining the same MIC90 of 2 mg/L against the carbapenem-resistant strains.
Saeed, M.; Hussain, S.; Ahmad, A.
To evaluate the pathogen burden and antibiotic-resistance trends of Pseudomonas aeruginosa among hospitalised patients at a tertiary care hospital. Study Design:Retrospective, hospital record-based, cross-sectional study. Place and Duration of Study:Microbiology Laboratory, Allama Iqbal Medical College/Jinnah Hospital, Lahore, from January 2014 to December 2016. Methodology:A total of 5,960 samples were collected from clinically suspected cases of bacterial infections, admitted to the hospital. Microbial identification and antibiotic susceptibility pattern were carried out and analysed. Results:Out of a total of 5,960 samples, Pseudomonas aeruginosawas isolated from 1,268 (21.2%) specimens. Department-wise isolation rate was n=600 (42.9%), n=268 (15.4%), n=201 (12.6%), and n=199 (16.0%) from intensive care unit (ICU), surgical units, medical units, and Gynae wards, respectively (p<0.0001). Sample-wise isolation rate was, wound swabs n=448 (35%), urine n=356 (28%), sputum n=187 (14 %), tracheal aspirate n=127 (10%), blood n=99 (7%), and broncho-alveolar lavage n=51 (4%) (p<0.0001). Drug-resistance pattern showed low rates for carbapenems (meropenem n=440 (35%), Imipenem n=436 (34%) and beta-lactam + beta-lactamase inhibitor combination (piperacillin+ tazobactam n=437 (34%) while alarming rates were observed for cephalosporins (ceftazidime n=716 (56%), fluoroquinolones (ciprofloxacin n=690 (54%), cefoperazone+sulbactam n=685 (54%), aminoglycosides (gentamicin, n=669 (53%), amikacin n=608 (48%), and monobactams (aztreonam n=666 (52%). Decreasing trend was observed only for amikacin 63% to 37%, aztreonam showed similar pattern throughout, while there was an increasing trend of drug resistance in all groups of antibiotics. Conclusion:Emerging drug-resistant strains of Pseudomonas aeruginosaare probably linked to the injudicious use of antibiotics, leading to ineffective empirical therapy. Therefore, we suggest that culture and antimicrobial susceptibility testing should
Liou, Bo-Huang; Duh, Ruay-Wang; Lin, Yi-Tsung; Lauderdale, Tsai-Ling Yang; Fung, Chang-Phone
Serratia marcescens is an important nosocomial pathogen and the characteristic property of resistance conferred by extended-spectrum beta-lactamase or a novel AmpC cephalosporinase was not unusual in Taiwan. This study investigated the trends in antimicrobial resistance in S. marcescens from a nationwide surveillance in Taiwan. S. marcescens isolates were collected biennially between 2002 and 2010 from medical centers and regional hospitals throughout Taiwan, as part of the Taiwan Surveillance of Antimicrobial Resistance program. Minimal inhibitory concentrations were determined by the Clinical and Laboratory Standards Institute reference broth microdilution method. A total of 403 nonduplicate S. marcescens isolates were collected, mostly from respiratory samples (157, 39.0%), followed by the urinary tract samples (90, 22.3%). Overall, 99.3% isolates were susceptible to imipenem, 93.8% to ceftazidime, 89.2% to minocycline, 87.8% to amikacin, 86.8% to cefepime, 82.9% to aztreonam, 73.2% to ceftriaxone, 72.7% to levofloxacin, 63.8% to ciprofloxacin, 60.8% to trimethoprim/sulfamethoxazole (TMP/SMX), and 59.6% to gentamicin. A significantly increased susceptibility rate after 2004 was observed for the following antibiotics: amikacin (73.8% vs. 97.1%), gentamicin (40.0% vs. 72.4%), ciprofloxacin (53.8% vs. 70.4%), ceftriaxone (53.8% vs. 86.0%), cefepime (74.4% vs. 95.1%), aztreonam (72.5% vs. 89.7%), and TMP/SMX (41.3% vs. 73.7%). In this 8-year study, the susceptibility of S. marcescens to ceftazidime and imipenem remained consistently high in Taiwan. S. marcescens isolates demonstrated relatively higher resistance to ciprofloxacin and levofloxacin, and therefore continued surveillance of antimicrobial resistance, especially for fluoroquinolone, is warranted. Copyright © 2013. Published by Elsevier B.V.
Gabriele Mariani Machado
Full Text Available INTRODUÇÃO: O principal mecanismo de resistência entre isolados de Pseudomonas aeruginosa e Acinetobacter sp. é a produção de metalo-β-lactamases (MβLs. As MβLs são enzimas capazes de hidrolisar cefalosporinas, penicilinas e carbapenêmicos, mas não monobactâmicos (aztreonam antibióticos que se encontram entre as principais opções terapêuticas para o tratamento de infecções causadas por bactérias não fermentadoras de glicose. MÉTODOS: Um estudo observacional, transversal, descritivo e retrospectivo foi desenvolvido para avaliar a frequência e o perfil de susceptibilidade cepas de P. aeruginosa e Acinetobacter sp. produtoras de MβLs isoladas no Hospital São Vicente de Paulo, Passo Fundo, Brasil. RESULTADOS: A produção de MβLs foi observada em 77,6% (n = 173/223 dos isolados de P. aeruginosa e em 22,4% (n = 50/223 dos isolados de Acinetobacter sp. Dentre as cepas produtoras de MβL, a maioria apresentou mais de 90% de resistência a seis antimicrobianos dos 12 testados, enfatizando a resistência a ceftazidima, gentamicina, aztreonam, piperaciclina/tazobactam, cefepime, ciprofloxacina, meropenem e tobramicina. CONCLUSÕES: Os índices de MβL encontrados confirmam a preocupação mundial com a disseminação desse mecanismo de resistência.
Isoken Henrietta Igbinosa
Full Text Available Objective: To characterize multiple antibiotic resistance profile of Pseudomonas aeruginosa from aquaculture and abattoir environments. Methods: Wastewater samples were obtained from the abattoir and aquaculture environments between May 2016 and July 2016 and analysed using standard phenotypic, biochemical and PCR-based methods. Results: The mean pseudomonads count ranged from (4 × 102 ± 1.01 to (2 × 104 ± 0.10 colony-forming unit/mL in the aquaculture environment and (3 × 103 ± 0.00 to (1 × 105 ± 1.00 colony-forming unit/mL in the abattoir environment. A total of 96 isolates of Pseudomonas aeruginosa confirmed by PCR were thereafter selected from both aquaculture and abattoir environments and further characterized for their antimicrobial susceptibility profile by adopting the disc diffusion method. High level of resistance was observed against the aminoglycosides [gentamycin 64/96 (66.67% and kanamycin 52/96 (54.17%], monobactams [aztreonam 76/96 (79.17%], carbapenems [meropenem 52/96 (54.17%], tetracyclines [tetracycline 72/96 (75.00%] and cephems [ceftazidime 72/96 (75.00% and cefuroxime 48/96 (50.00%]. Multiple antibiotic resistant index of the respective isolates ranged from 0.4 to 0.8 while multidrug resistant profile of the isolates revealed that 28 of the respective isolates were resistant to ceftazidime, cefuroxime, gentamycin, kanamycin, aztreonam which belongs to cephems, aminoglycosides and monobactam class of antimicrobials. Conclusions: Findings from the present study therefore underscores the need for effective monitoring of the abattoir and aquaculture environments as they could be the significant source for spreading antibiotic resistant bacteria within the environment.
Bedenic, B; Vranes, J; Mihaljevic, Lj; Tonkic, M; Sviben, M; Plecko, V; Kalenic, S
The aim of this study was to compare the sensitivity and specificity of six different beta-lactam antibiotics using five phenotypical tests for detection of extended spectrum beta-lactamases (ESBLs) based on synergism of beta-lactam antibiotics and clavulanate. Experiments were performed on a set of 80 Klebsiella pneumoniae strains and 105 Escherichia coli strains with previously characterized ESBLs (SHV, TEM and CTX-M). ESBLs were detected by five different phenotypical methods: MIC (minimum inhibitory concentration) determination of beta-lactam antibiotics with and without clavulanate, double-disk synergy test (DDST), inhibitor-potentiated disk-diffusion test (IPDDT), CLSI-Clinical and Laboratory Standard Institution (former NCCLS) combined-disk-test, and modified MAST-disk-diffusion test (MAST-DD-test). Seven antibiotics were tested as indicators of ESBL production: ceftazidime, cefotaxime, ceftriaxone, aztreonam, ceftibuten, cefpodoxime and cefepime. Ceftazidime and aztreonam were the best indicators for SHV-5, SHV-12 and TEM beta-lactamases whereas cefotaxime and ceftriaxone were the most sensitive in detection of SHV-2 and CTX-M beta-lactamases in DDST, IPDDT and CLSI test. MIC determination of beta-lactam antibiotics with and without clavulanate was the most sensitive method. DDST was the least sensitive test. Double-disk synergy test, which is the most frequently used test for detection of ESBLs in routine laboratories, was the least sensitive independently of the indicator antibiotic. Since MIC determination is a very laborious and time consuming method, we would recommend the NCCLS combined disk test or IPDD test for detection of ESBLs in routine laboratories with 5 mm zone augmentation breakpoint.
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
Ishii, Y; Ohno, A; Taguchi, H; Imajo, S; Ishiguro, M; Matsuzawa, H
Escherichia coli TUH12191, which is resistant to piperacillin, cefazolin, cefotiam, ceftizoxime, cefuzonam, and aztreonam but is susceptible to cefoxitin, latamoxef, flomoxef, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-1) purified from the bacteria had a pI of 7.8, had a molecular weight of about 29,000, and hydrolyzed beta-lactam antibiotics such as penicillin G, ampicillin, oxacillin, carbenicillin, piperacillin, cephalothin, cefoxitin, cefotaxime, ceftazidime, and aztreonam. Toho-1 was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid and tazobactam. Resistance to beta-lactams, streptomycin, spectinomycin, sulfamethoxazole, and trimethoprim was transferred by conjugational transfer from E. coli TUH12191 to E. coli ML4903, and the transferred plasmid was about 58 kbp, belonging to incompatibility group M. The cefotaxime resistance gene for Toho-1 was subcloned from the 58-kbp plasmid by transformation of E. coli MV1184. The sequence of the gene for Toho-1 was determined, and the open reading frame of the gene consisted of 873 or 876 bases (initial sequence, ATGATG). The nucleotide sequence of the gene (DDBJ accession number D37830) was found to be about 73% homologous to the sequence of the gene encoding a class A beta-lactamase produced by Klebsiella oxytoca E23004. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 290 or 291 amino acid residues, which contained amino acid motifs common to class A beta-lactamases (70SXXK, 130SDN, and 234KTG). Toho-1 was about 83% homologous to the beta-lactamase mediated by the chromosome of K. oxytoca D488 and the beta-lactamase mediated by the plasmid of E. coli MEN-1. Therefore, the newly isolated beta-lactamase Toho-1 produced by E. coli TUH12191 is similar to beta-lactamases produced by K. oxytoca D488, K. oxytoca E23004, and E. coli MEN-1 rather than to mutants of TEM or SHV enzymes
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Eighty nine bacterial strains isolated from newborn infants hospitalized at a Special Care Unit in Medellin, Colombia, were studied. The sensitivity of each one was determined by the Minimallnhibitory Concentration method against 21 antibiotics; a high frequency of resistance was found toward gentamycin, netilmycin, oxacillin, penicillin G and ampicillin, that are often employed as initial therapy in newborn infants; on the other hand both Gram positive and Gram negative bacteria exhibited high percentages of sensitivity against quinolones; aztreonam and third generation cephalosporins were also highly effective against Gram negative bacilli. On the basis of this new information the need to restate therapeutic conducts in the case of serious bacterial neonatal infections is emphasized.
Se estudiaron 89 cepas bacterianas aisladas de neonatos hospitalizados en la sala de cuidados especiales de la Fundación Hospitalaria San Vicente de Paúl, de Medellín; a cada una se le determinó la sensibilidad frente a 21 antibióticos por el método de la concentración inhibitoria mínima (CIM; se halló una alta frecuencia de resistencia hacia la gentamicina, la netilmicina, la oxacilina y la ampicilina que se usan a menudo en esta institución como terapia inicial en las infecciones del recién nacido; por otra parte se demostraron altos porcentajes de sensibilidad hacia las quinolonas tanto de las bacterias gram positivas como de las gram negativas; contra estas últimas también fueron muy efectivos el aztreonam y las cefalosporinas de tercera generación. A la luz de esta nueva información se llama la atención hacia la necesidad de revaluar las normas de la antibioterapia en las infecciones graves del recién nacido.
Lina María Echeverri Toro
Full Text Available The antimicrobial resistance is an increasing problem of public health. Klebsiella pneumoniae has become one of the most important pathogens because it is a frequent cause of nosocomial and community acquired infections and it has pathogenicity mechanisms like capsules, adhesive properties mediated by specialized estructures (pillis and siderophores that are capable of taking up iron, an essential factor in bacterial growth. The increase in bacterial resistance to antibiotics has evolved with the use of these in patients treatments, being increasingly wide the spectrum that they include, happening from the resistance to ampicillin by the production of betalactamase SHV-1 to carbapenems resistance by diverse mechanisms, from the production of extendedspectrum betalactamases (ESBL that are associated with hydrolysis of extended-spectrum cephalosporins and aztreonam. Microbiology laboratory should follow international recommendations to detect and confirm the presence of this resistance mechanism in bacteria and the clinicians should make a suitable interpretation of the results to make the better choice of the antibiotic therapy. ----- La resistencia de los microorganismos a los antibióticos es un problema cada vez creciente en salud pública. Entre estos, Klebsiella pneumoniae es un representante importante no sólo por su frecuencia como causa de infecciones asociadas al cuidado de la salud y de la comunidad, sino por los mecanismos patogénicos que posee, como la capacidad de producir cápsula, la presencia de estructuras especializadas que le permiten adherirse a las células del hospedero (pilis, y de sideróforos que le permiten obtener el hierro necesario para su desarrollo. La resistencia de Klebsiella pneumoniae a los antimicrobianos ha evolucionado de acuerdo con la aparición y uso de estas moléculas en el tratamiento de los pacientes, siendo cada vez más amplio el espectro que abarcan, el cual va desde la resistencia a la ampicilina
Masuda, Nobuhisa; Sakagawa, Eiko; Ohya, Satoshi; Gotoh, Naomasa; Tsujimoto, Hideto; Nishino, Takeshi
To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the following substrate specificities. All of the efflux systems extrude a wide variety of antimicrobial agent groups, i.e., quinolones, macrolides, tetracyclines, lincomycin, chloramphenicol, most penicillins (all but carbenicillin and sulbenicillin), most cephems (all but cefsulodin and ceftazidime), meropenem, and S-4661, but none of them extrude polymyxin B or imipenem. Extrusion of aminoglycosides is specific to MexXY-OprM, and extrusion of a group of the β-lactams, i.e., carbenicillin, sulbenicillin, ceftazidime, moxalactam, and aztreonam, is specific to MexAB-OprM. Moreover, MexAB-OprM and MexCD-OprJ extrude novobiocin, cefsulodin, and flomoxef, while MexXY-OprM does not. These substrate specificities are distinct from those reported previously. PMID:11083635
Butt, T.; Butt, E.; Raza, S.
This descriptive and cross-sectional study was planned to determine the dilemma of inadvertent detection of extended spectrum beta lactamase (ESBL) production in Enterobacteriaceaewhen using inhibition zone size of antibiotic disks of Cefotaxime or Aztreonam in routine antibiotic susceptibility testing as recommended by Clinical Laboratory Standards Institute (CLSI). Screening and double disk tests were adopted as per CLSI. Escherichia coli ATCC 25922 was used as control strain. Among total specimens of 5346, there were 348 isolates of Escherichia coli(n=235), Klebsiella pneumonia (n=92), Klebsiella oxytoca(n=3) or Proteus mirabilus(n=18). The screening method recommended by CLSI significantly falsely detected ESBL production in 79 (32.3%) isolates (p<0.0001). ESBL detection is important as its frequency is high and treatment of the infection varies with the presence and absence of ESBL. To avoid false reporting, proper phenotypic detection of ESBL confirmatory method-like double-disk synergy test, should be used routinely. (author)
Full Text Available Pulmonary infections by Gram-negative bacteria such as Achromobacter xylosoxidans are recovered frequently in patients with Cystic Fibrosis. Aims of this study were to value the isolation frequency of A.xylosoxidans strains in a cohort of Cystic Fibrosis patients, to investigate their antimicrobial sensitivity and to establish possible clonal likeness among strains.A retrospective study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Centre of “Federico II” University, Naples. Sputum samples were collected and selective media as well as commercial systems for bacterial identification were used. The activity of antimicrobial agents was determined using diffusion and micro-dilution methods. For DNA-fingerprinting, a genomic DNA macrorestriction followed by pulsed-field gel electrophoresis was carried out. A total of 238 strains from 51 patients were isolated. Strains were resistant to aztreonam, about half of these were resistant to gentamicin and trimethoprim-sulphamethoxazole. They were sensitive to piperacillin, piperacillin/tazobactam, and also to carbapenems, quinolones, cephalosporines. Macrorestriction analysis applied on some isolates showed substantial heterogeneity among strains.Actually, the prognostic role of A. xylosoxidans in Cystic Fibrosis is unclear, but this finding must imply difficulties on therapeutic approach. So, it is need to be on the look out regard such microorganisms. Preliminary results of DNA-fingerprinting indicate no evidence of clonal likeness and then of patient-to-patient spread.
Dong, Fang; Xu, Xi-wei; Song, Wen-qi; Lü, Ping; Yang, Yong-hong; Shen, Xu-zhuang
To analyze the antibiotic resistance of the Pseudomonas aeruginosa (PA) isolated from pediatric patients and the resistant genes of beta-lactam antibiotics thereof. 146 PA strains were isolated from pediatric patients. Agar dilution method recommended by the Clinical and Laboratory Standards Institute was used to examine the minimum inhibitory concentrations (MICs) of 12 antimicrobial agents, including the penicillins, third and fourth genet ration cephalosporins, carbapenemase, Aztreonam, beta-lactamase inhibitors, quinolones, and aminoglycosides. PCR was used to detect the expression of the genes TEM, SHV, OXA, PER, GES, CTX-M, IMP, VIM, DHA, MIR, FOX, and oprD2. The multi-drug resistance rates against different antibiotic were high among the 146 PA strains. The rates of imipenem and meropenem resistance were 41.1% and 35.6% respectively. Among the 146 PA strains, 46 (31.5%) were positive for the MBL genotype; 38 (82.6%) carried the blaIMP gene, 8 (17.4%) carried the blaVIM gene, and 114 (78.1%) were oprD2 negative. The genes TEM, SHV, OXA, CTX-M, PER, VEB, GES, FOX, MIR, and DHA were not found in all strains. Many PA isolated from pediatric patients carry the genes IMP or VIM and losses oprD2 gene related to the expression of the outer membrane porin OprD2. The loss of the gene oprD2 is essential mechanism of beta-lactam antibiotics resistance in PA.
Full Text Available Aims and Objectives: It has been observed that various microorganisms are acquiring resistance to most of the available potent antibiotics; hence, there is a need for every hospital to follow the use of antibiotics according to antibiotic sensitivity pattern in that particular hospital or geographical area. It has been reported that Enterobacteriaceae group of microorganisms are increasingly acquiring resistance to many antibiotics and this resistance varies geographically. As there is a short of recent data with respect to Indian hospital, this particular study was designed with the aim of establishing sensitivity pattern of Enterobacteriaceae group of microorganisms to various antibiotics. Materials and Methods: Data of antibiotic sensitivity from December 2010 to April 2011 of different Enterobacteriaceae was taken from the Department of Microbiology, Govt. Medical College, Surat. Sensitivity of different Enterobacteriaceae was shown as using descriptive statistics. Results: E. coli (55.6% and Klebsiella (31.2% were the most frequent bacteria isolated. Enterobacteriaceae were very less sensitive to amoxicillin + clavulanic acid (13.7%, chloramphenicol (7.6%, cefoperazone (14.4%, cefixime (15.7%, and cefuroxime (17.6. Sensitivity to aztreonam was 32.7%. Sensitivity to carbapenem group of drugs included in this study, i.e., meropenem was 69.8%. Highest sensitivity was shown for ceftazidime (74.1%. E. coli is more sensitive to meropenem as compared with Klebsiella. Conclusion: Sensitivity of Enterobacteriaceae group of microorganisms to known antibiotics is decreasing. Decreased sensitivity to carbapenem group of antibiotics is a matter of concern.
Full Text Available A carbapenem-resistant strain of Pseudomonas aeruginosa, NCGM1984, was isolated in 2012 from a hospitalized patient in Japan. Immunochromatographic assay showed that the isolate was positive for IMP-type metallo-β-lactamase. Complete genome sequencing revealed that NCGM1984 harbored two copies of blaIMP-34, located at different sites on the chromosome. Each blaIMP-34 was present in the same structures of the class 1 integrons, tnpA(ISPa7-intI1-qacG-blaIMP-34-aac(6'-Ib-qacEdelta1-sul1-orf5-tniBdelta-tniA. The isolate belonged to multilocus sequence typing ST235, one of the international high-risk clones. IMP-34, with an amino acid substitution (Glu126Gly compared with IMP-1, hydrolyzed all β-lactamases tested except aztreonam, and its catalytic activities were similar to IMP-1. This is the first report of a clinical isolate of an IMP-34-producing P. aeruginosa harboring two copies of blaIMP-34 on its chromosome.
Hong, Myoung-Ki; Lee, Jae Jin; Wu, Xing; Kim, Jin-Kwang; Jeong, Byeong Chul; Pham, Tan-Viet; Kim, Seung-Hwan; Lee, Sang Hee; Kang, Lin-Woo
The SFC-1 gene from S. fonticola was cloned and SFC-1 was expressed, purified and crystallized. X-ray diffraction data were collected from an SFC-1 crystal to 1.6 Å resolution. SFC-1, a class A carbapenemase that confers antibiotic resistance, hydrolyzes the β-lactam rings of β-lactam antibiotics (carbapenems, cephalosporins, penicillins and aztreonam). SFC-1 presents an enormous challenge to infection control, particularly in the eradication of Gram-negative pathogens. As SFC-1 exhibits a remarkably broad substrate range, including β-lactams of all classes, the enzyme is a potential target for the development of antimicrobial agents against pathogens producing carbapenemases. In this study, SFC-1 was cloned, overexpressed, purified and crystallized. The SFC-1 crystal diffracted to 1.6 Å resolution and belonged to the orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 65.8, b = 68.3, c = 88.8 Å. Two molecules are present in the asymmetric unit, with a corresponding V M of 1.99 Å 3 Da −1 and a solvent content of 38.1%
Full Text Available Since about twenty years, following the introduction into therapeutic of news beta-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems, a very significant number of new beta-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-beta-enzymes (IMP, VIM, SPM, GIM types are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all beta-lactamases because they confer resistance to carbapenems and all the beta-lactams (with the exception of aztreonam and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended--spectrum antibiotics (e.g. cephalosporins and carbapenems, and therefore care must be taken that these drugs are not used unnecessarily.
Luczkiewicz, Aneta; Kotlarska, Ewa; Artichowicz, Wojciech; Tarasewicz, Katarzyna; Fudala-Ksiazek, Sylwia
In this study, species distribution and antimicrobial susceptibility of cultivated Pseudomonas spp. were studied in influent (INF), effluent (EFF), and marine outfall (MOut) of wastewater treatment plant (WWTP). The susceptibility was tested against 8 antimicrobial classes, active against Pseudomonas spp.: aminoglycosides, carbapenems, broad-spectrum cephalosporins from the 3rd and 4th generation, extended-spectrum penicillins, as well as their combination with the β-lactamase inhibitors, monobactams, fluoroquinolones, and polymyxins. Among identified species, resistance to all antimicrobials but colistin was shown by Pseudomonas putida, the predominant species in all sampling points. In other species, resistance was observed mainly against ceftazidime, ticarcillin, ticarcillin-clavulanate, and aztreonam, although some isolates of Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudoalcaligenes, and Pseudomonas protegens showed multidrug-resistance (MDR) phenotype. Among P. putida, resistance to β-lactams and to fluoroquinolones as well as multidrug resistance become more prevalent after wastewater treatment, but the resistance rate decreased in marine water samples. Obtained data, however, suggests that Pseudomonas spp. are equipped or are able to acquire a wide range of antibiotic resistance mechanisms, and thus should be monitored as possible source of resistance genes.
Full Text Available Acinetobacter species are aerobic Gram variable coccobacilli that are now emerging as an important nosocomial pathogen. Infections caused by them are difficult to control due to multidrug resistance. The purpose of this study was to detect virulence factors namely gelatinase production, biofilm formation and antibiotic susceptibility of Acinetobacter species. Two hundred fifty six clinical samples collected from Bangabandhu Sheikh Mujib medical University (BSMMU and from burn unit of Dhaka Medical College Hospital were included in the study. Gelatinase production was seen on Luria Bertani agar media containing gelatin (30 gm/l and biofilm formation was detected in microtiter plate assay. Out of 256 clinical samples, 52 (20.3% were Acinetobacter species. Out of 52 Acinetobacter isolates, none were gelatinase producer but 39 (75% were found biofilm producers. Acinetobacter isolates were 100% resistant to ceftazidime, cefotaxime cefuroxime and ceftriaxone. High level of resistance was also recorded for amoxicillin (98.1%, aztreonam (98.1%, gentamicin (90.4%, ciprofloxacin (73.1%, amikacin (57.6%, netilmicin (53.8% and imipenem (44.2%. Susceptibility to colistin was maximum (96.2%. The present study demonstrated a high propensity of biofilm formation by the clinical isolates of Acinetobacter species and most of the Acinetobacter were multidrug resistant. Ibrahim Med. Coll. J. 2012; 6(1: 27-30
Alain C. Juayang
Full Text Available Over five years, a total of 646 P. aeruginosa isolates was acquired from different clinical specimens and their resistance to the commonly used anti-pseudomonal antibiotics was determined. The majority of the isolates were from respiratory (60.99% and urinary sources (23.22% while the least came from transudates and exudates (2.01%. Most of the samples were acquired from older adults (77.55%, most of whom were admitted (67.03%. Amikacin was found to be the most effective drug with a resistance rate of 7.5%, followed by piperacillin/tazobactam (8.5% and gentamicin (13.5%. On the other hand, 26.7% of the isolates were resistant to levofloxacin. Almost 100% of the isolates were screened positive for AmpC production, which may suggest inducible resistance against expanded spectrum beta-lactamase. Furthermore, for the last three years, P. aeruginosa isolates from this area have been noted to have decreasing resistance only to aztreonam and gentamicin. Also, for five years, a mean MAR index of 0.17 was noted which indicates either proper antibiotic use or most isolates did not come from high-risk areas. Moreover, there was no significant difference in the resistance of P. aeruginosa when compared by specimen source (p = 0.662, but significant when compared by year band (p = 0.02.
Full Text Available With the increased focus on healthy eating and consuming raw vegetables, this study assessed the extent of contamination of fresh vegetables by Pseudomonas aeruginosa in Jamaica and examined the antibiotic susceptibility profiles and the presence of various virulence associated determinants of P. aeruginosa. Analyses indicated that vegetables from retail markets and supermarkets were widely contaminated by P. aeruginosa; produce from markets were more frequently contaminated, but the difference was not significant. Lettuce and carrots were the most frequently contaminated vegetables, while tomatoes were the least. Pigment production (Pyoverdine, pyocyanin, pyomelanin and pyorubin, fluorescein and alginate were common in these isolates. Imipenem, gentamicin and ciprofloxacin were the most inhibitory antimicrobial agents. However, isolates were resistant or showed reduced susceptibility to ampicillin, chloramphenicol, sulphamethoxazole/trimethoprim and aztreonam, and up to 35% of the isolates were resistant to four antimicrobial agents. As many as 30% of the isolates were positive for the fpv1 gene, and 13% had multiple genes. Sixty-four percent of the isolates harboured an exoenzyme gene (exoS, exoT, exoU or exoY, and multiple exo genes were common. We conclude that P. aeruginosa is a major contaminant of fresh vegetables, which might be a source of infection for susceptible persons within the community.
José R. Mediavilla
Full Text Available Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.
Full Text Available Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract of Juglans regia tree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract of J. regia bark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria, Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30% in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action of J. regia extract against multiple drug-resistant bacteria when tested with a range of antibiotics.
D'Aimmo, Maria Rosaria; Modesto, Monica; Biavati, Bruno
The outlines of antibiotic resistance of some probiotic microorganisms were studied. This study was conducted with the double purpose of verifying their ability to survive if they are taken simultaneously with an antibiotic therapy and to increase the selective properties of suitable media for the isolation of samples containing mixed bacterial populations. We isolated from commercial dairy and pharmaceutical products, 34 strains declared as probiotics, belonging to the genera Bifidobacterium and Lactobacillus, and 21 strains of starter culture bacteria. All the microorganisms have been compared by electrophoresis of the soluble proteins for the purpose of identifying them. A Multiplex-PCR with genus- and species-specific primers was used to detect for Bifidobacterium animalis subsp. lactis presence. All bifidobacteria were B. animalis subsp. lactis except one Bifidobacterium longum. Sometimes the identification showed that the used strain was not the one indicated on the label. The lactobacilli were Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus delbrueckii subsp. bulgaricus. The streptococci were all Streptococcus thermophilus. The minimal inhibitory concentration (MIC) of 24 common antibiotic substances has been valued by the broth microdilution method. All tested strains were susceptible to ampicillin, bacitracin, clindamycin, dicloxacillin, erytromycin, novobiocin, penicillin G, rifampicin (MIC(90) ranging from 0.01 to 4 microg/ml); resistant to aztreonam, cycloserin, kanamycin, nalidixic acid, polymyxin B and spectinomycin (MIC(90) ranging from 64 to >1000 microg/ml). The susceptibility to cephalothin, chloramphenicol, gentamicin, lincomycin, metronidazole, neomycin, paromomycin, streptomycin, tetracycline and vancomycin was variable and depending on the species.
Khan, M.A.; Ashshi, A.M.; Mahomed, M.F.
Background: Acinetobacter baumannii causes infections of respiratory, urinary tract, blood stream and surgical sites. Its clinical significance has increased due to its rapidly developing resistance to major groups of antibiotics used for its treatment. There is limited data available on antimicrobial susceptibility of A. baumannii from Saudi Arabia. Objectives: To determine the patterns of drug resistance of Acinetobacter baumannii and predisposing factors for its acquisition.Subjects and Methods: In this descriptive study, 72 hospitalized patients infected with A baumannii were studied. The clinical and demographic data of the patients were collected using a predesigned questionnaire. Isolation and identification of A.baumannii from all clinical specimens were done using standard microbiological methods. Antibiotic susce ptibility testing was performed by disk diffusion method recommended by Clinical Laboratory Standards Institute. Results: Majority of the isolates (61.1%) were from respiratory tract infections. A.baumannii isolates showed high drug resistance to piperacil lin (93.1%), aztreonam (80.5%), ticarcillin, ampicillin, and tetracycline (76.4%, each) and cefotaxime (75%). Only amikacin showed low rate of resistance compared to other antibiotics (40.3%). About 36% patients had some underlying diseases with diabetes mellitus (11%) being the predominant underlying disease. Conclusions: High antimicrobial resistance to commonly used antibiotics was seen against A.baumannii isolates. Only amikacin was most effective against it. (author)
Multiple-locus variable number of tandem repeats (VNTR) fingerprinting (MLVF) and antibacterial resistance profiles of extended spectrum beta lactamase (ESBL) producing Pseudomonas aeruginosa among burnt patients in Tehran.
Jabalameli, Fereshteh; Mirsalehian, Akbar; Sotoudeh, Nazli; Jabalameli, Leila; Aligholi, Marzieh; Khoramian, Babak; Taherikalani, Morovat; Emaneini, Mohammad
Extended spectrum β-lactamase (ESBL)-producing trait was present in 48 out of the 112 (42.8%) Pseudomonas aeruginosa isolates collected from burn wound infections during a 12-month period. The presence of oxa-10, per-1, veb-1 and ges genes and the multiple-locus variable number of tandem repeats (VNTR) fingerprinting (MLVF) of 112 P. aeruginosa strains were determined by PCR and multiplex PCR. Disk diffusion methods were used to determine the susceptibility of the isolates to antimicrobial agents as instructed by CLSI. All ESBL isolates were resistant to aztreonam, cefepime, cefotaxime, cefpodoxime, ceftazidime, ceftriaxone and ofloxacin. Fewer than 60% of ESBL isolates were resistant to imipenem, meropenem, and piperacillin-tazobactam but more than 90% were resistant to amikacin, ciprofloxacin, levofloxacin, ticarcillin and tobramycin. The most prevalent ESBL genes included oxa-10 (70%) and per-1 (50%) followed by veb-1 (31.3%). The gene encodes GES enzyme did not detect in any isolates. A total of 100 P. aeruginosa strains were typed by MLVF typing method. MLVF produced 42 different DNA banding patterns. These data indicate that different MLVF types infect burn wounds in patients at a hospital in Tehran and also suggest an alarming rate of ESBL-producing isolates in this test location. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.
Wong, Aloysius Tze
Background Probiotics are live microorganisms that confer nutrition- and health-promoting benefits if consumed in adequate amounts. Concomitant with the demand for natural approaches to maintaining health is an increase in inclusion of probiotics in food and health products. Since probiotic bacteria act as reservoir for antibiotic resistant determinants, the transfer of these genes to pathogens sharing the same intestinal habitat is thus conceivable considering the fact that dietary supplements contain high amounts of often heterogeneous populations of probiotics. Such events can confer pathogens protection against commonly-used drugs. Despite numerous reports of antibiotic resistant probiotics in food and biological sources, the antibiogram of probiotics from dietary supplements remained elusive. Findings Here, we screened five commercially available dietary supplements for resistance towards antibiotics of different classes. Probiotics of all batches of products were resistant towards vancomycin while batch-dependent resistance towards streptomycin, aztreonam, gentamycin and/or ciprofloxacin antibiotics was detected for probiotics of brands Bi and Bn, Bg, and L. Isolates of brand Cn was also resistant towards gentamycin, streptomycin and ciprofloxacin antibiotics. Additionally, we also report a discrepancy between the enumerated viable bacteria amounts and the claims of the manufacturers. Conclusions This short report has highlighted the present of antibiotic resistance in probiotic bacteria from dietary supplements and therefore serves as a platform for further screenings and for in-depth characterization of the resistant determinants and the molecular machinery that confers the resistance.
Tiwari, Vishvanath; Nagpal, Isha; Subbarao, Naidu; Moganty, Rajeswari R
Acinetobacter baumannii, one of the major Gram negative bacteria, causes nosocomial infections such as pneumonia, urinary tract infection, meningitis, etc. β-lactam-based antibiotics like penicillin are used conventionally to treat infections of A. baumannii; however, they are becoming progressively less effective as the bacterium produces diverse types of β-lactamases to inactivate the antibiotics. We have recently identified a novel β-lactamase, OXA-51 from clinical strains of A. baumannii from our hospital. In the present study, we generated the structure of OXA-51 using MODELLER9v7 and studied the interaction of OXA-51 with a number of β-lactams (penicillin, oxacillin, ceftazidime, aztreonam and imipenem) using two independent programs: GLIDE and GOLD. Based on the results of different binding parameters and number of hydrogen bonds, interaction of OXA-51 was found to be maximum with ceftazidime and lowest with imipenem. Further, molecular dynamics simulation results also support this fact. The lowest binding affinity of imipenem to OXA-51 indicates clearly that it is not efficiently cleaved by OXA-51, thus explaining its high potency against resistant A. baumannii. This finding is supported by experimental results from minimum inhibitory concentration analysis and transmission electron microscopy. It can be concluded that carbapenems (imipenem) are presently effective β-lactam antibiotics against resistant strains of A. baumannii harbouring OXA-51. The results presented here could be useful in designing more effective derivatives of carbapenem.
Wong, Aloysius Tze
Abstract Background Probiotics are live microorganisms that confer nutrition- and health-promoting benefits if consumed in adequate amounts. Concomitant with the demand for natural approaches to maintaining health is an increase in inclusion of probiotics in food and health products. Since probiotic bacteria act as reservoir for antibiotic resistant determinants, the transfer of these genes to pathogens sharing the same intestinal habitat is thus conceivable considering the fact that dietary supplements contain high amounts of often heterogeneous populations of probiotics. Such events can confer pathogens protection against commonly-used drugs. Despite numerous reports of antibiotic resistant probiotics in food and biological sources, the antibiogram of probiotics from dietary supplements remained elusive. Findings Here, we screened five commercially available dietary supplements for resistance towards antibiotics of different classes. Probiotics of all batches of products were resistant towards vancomycin while batch-dependent resistance towards streptomycin, aztreonam, gentamycin and/or ciprofloxacin antibiotics was detected for probiotics of brands Bi and Bn, Bg, and L. Isolates of brand Cn was also resistant towards gentamycin, streptomycin and ciprofloxacin antibiotics. Additionally, we also report a discrepancy between the enumerated viable bacteria amounts and the claims of the manufacturers. Conclusions This short report has highlighted the present of antibiotic resistance in probiotic bacteria from dietary supplements and therefore serves as a platform for further screenings and for in-depth characterization of the resistant determinants and the molecular machinery that confers the resistance.
Yong, Dongeun; Toleman, Mark A; Bell, Jan; Ritchie, Brett; Pratt, Rachael; Ryley, Henry; Walsh, Timothy R
Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837) isolated from the Women's and Children's Hospital, Adelaide, Australia, produced a metallo-β-lactamase (MBL)-positive Etest result. All isolates were PCR negative for known MBL genes. A gene bank was created, and an MBL gene, designated bla(AIM-1), was cloned and fully characterized. The encoded enzyme, AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1. It is chromosomal and flanked by two copies (one intact and one truncated) of an ISCR element, ISCR15. Southern hybridization studies indicated the movement of both ISCR15 and bla(AIM-1) within the three different clinical isolates. AIM-1 hydrolyzes most β-lactams, with the exception of aztreonam and, to a lesser extent, ceftazidime; however, it possesses significantly higher k(cat) values for cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group B3 enzyme detected and signals further problems for already beleaguered antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative infections.
Wang, Jun; He, Lijiao; Sha, Jintong; Zhu, Haobo; Huang, Liqu; Zhu, Xiaojiang; Dong, Jun; Li, Guogen; Ge, Zheng; Lu, Rugang; Ma, Geng; Shi, Yaqi; Guo, Yunfei
Urinary tract infection (UTI) is one of most common pediatric infections. The aim of this study was to investigate the etiology and antimicrobial resistance patterns in children hospitalized at Children's Hospital of Nanjing Medical University. We conducted a retrospective, descriptive study of all UTI from 1 January 2013 to 30 November 2016 in children discharged from Nanjing Children's Hospital. The isolated pathogens and their resistance patterns were examined using midstream urine culture. A total of 2,316 children with UTI were included in the study. The occurrence rates of isolated pathogens were as follows: Enterococcus spp., 35.15%; Escherichia coli, 22.32%; Staphylococcus aureus spp., 7.73%; Streptococcus spp., 7.51%; and Klebsiella spp., 6.95%. Uropathogens had a low susceptibility to linezolid (3.47%), vancomycin (0.92%), imipenem (5.74%), and amikacin (3.17%), but they had a high susceptibility to erythromycin (90.52%), penicillin G (74.01%), cefotaxime (71.41%), cefazolin (73.41%), cefuroxime (72.52%), and aztreonam (70.11%). There is high antibiotic resistance in hospitalized children with UTI. Susceptibility testing should be carried out on all clinical isolates, and the empirical antibiotic treatment should be altered accordingly. © 2018 Japan Pediatric Society.
Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu
Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p antibiotics ( p antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.
Afrah Kamal Yassin
Full Text Available Poultry and livestock are the most important reservoirs for pathogenic Escherichia coli and use of antimicrobials in animal farming is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms. The aim of our study was to investigate antimicrobial resistance in E. coli isolated from food animals in Jiangsu, China. The disc diffusion method was used to determine susceptibility to 18 antimicrobial agents in 862 clinical isolates collected from chickens, ducks, pigs, and cows between 2004 and 2012. Overall, 94% of the isolates showed resistance to at least one drug with 83% being resistance to at least three different classes of antimicrobials. The isolates from the different species were most commonly resistant to tetracycline, nalidixic acid, sulfamethoxazole, trimethoprim/sulfamethoxazole and ampicillin, and showed increasing resistance to amikacin, aztreonam, ceftazidime, cefotaxime, chloramphenicol, ciprofloxacin. They were least resistant to amoxicillin/clavulanic acid (3.4% and ertapenem (0.2%. MDR was most common in isolates from ducks (44/44, 100%, followed by chickens (568/644, 88.2%, pigs (93/113, 82.3% and cows (13/61, 21.3%. Our finding that clinical E. coli isolates from poultry and livestock are commonly resistant to multiple antibiotics should alert public health and veterinary authorities to limit and rationalize antimicrobial use in China.
Luczkiewicz, A; Fudala-Ksiazek, S; Jankowska, K; Quant, B; Olańczuk-Neyman, K
The occurrence of resistance patterns among wastewater fecal coliforms was determined in the study. Susceptibility of the isolates was tested against 19 antimicrobial agents: aminoglycosides, aztreonam, carbapenems, cephalosporines, beta-lactam/beta-lactamase inhibitors, penicillines, tetracycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. Additionally the removal of resistant isolates was evaluated in the laboratory-scale wastewater treatment model plant (M-WWTP), continuously supplied with the wastewater obtained from the full-scale WWTP. Number of fecal coliforms in raw (after mechanical treatment) and treated wastewater, as well as in aerobic chamber effluent was determined using selective medium. The selected strains were identified and examined for antibiotic resistance using Phoenix Automated Microbiology System (BD Biosciences, USA). The strains were identified as Escherichia coli (n=222), Klebsiella pneumoniae ssp. ozaenae (n=9), and Pantoea agglomerans (n=1). The isolate of P. agglomerans as well as 48% of E. coli isolates were sensitive to all antimicrobials tested. The most frequent resistance patterns were found for ampicillin: 100% of K. pneumoniae ssp. ozaenae and 41% of E. coli isolates. Among E. coli isolates 12% was regarded as multiple antimicrobial resistant (MAR). In the studied M-WWTP, the applied activated sludge processes reduced considerably the number of fecal coliforms, but increased the ratio of antimicrobial-resistant E. coli isolates to sensitive ones, especially among strains with MAR patterns.
Full Text Available Elda Righi, Alessia Carnelutti, Antonio Vena, Matteo Bassetti Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Abstract: The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA, are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. Keywords: bacterial skin and skin structure infections, multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus, delafloxacin
Full Text Available New Delhi metallo-β-lactmase-1 (NDM-1 has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiotics have been detected. It could effectively hydrolyze most β-lactams (k cat/K m ratios between 0.03 to 1.28 µmol⁻¹.s⁻¹, except aztreonam. We also found that thiophene-carboxylic acid derivatives could inhibit NDM-1 and have shown synergistic antibacterial activity in combination with meropenem. Flexible docking and quantum mechanics (QM study revealed electrostatic interactions between the sulfur atom of thiophene-carboxylic acid derivatives and the zinc ion of NDM-1, along with hydrogen bond between inhibitor and His189 of NDM-1. The interaction models proposed here can be used in rational design of NDM-1 inhibitors.
Full Text Available The objective of this work was the phylogenetic characterization of local clinical isolates of uropathogenic E. coli with respect to drug resistance. A total of 59 uropathogenic E. coli responsible for community acquired urinary tract infections were included in this study. A triplex PCR was employed to segregate each isolate into four different phylogenetic groups (A, B1, B2 and D. Drug resistance was evaluated by disc diffusion method. The drugs used were ampicillin, aztreonam, cefixime, cefoperazone, ceftriaxone, cephradine among β-lactam group; amikacin, gentamicin, and streptomycin among aminoglycosides; nalidixic acid and ciprofloxacin from quinolones; trimethoprim-sulfomethoxazole, and tetracycline. Among 59 uropathogenic E. coli isolates majority belonged to phylogenetic group B2 (50% where as 19% each belonged to groups A and B1, and 12% to group D. All the isolates were multiple drug resistant (MDR. Most effective drugs against Group A, B1, and B2 were gentamicin, amikacin and cefixime; ceftriaxone and quinolones; and ceftriaxone and amikacin, respectively. Group D isolates were found to be highly resistant to all drugs. Our results have shown emergence of MDR isolates among uropathogenic E. coli with dominance of phylogenetic group B2. However, it was found that group D isolates were though less frequent, more drug resistant as compared with group B2. Groups A and B1 were relatively uncommon. Amikacin, ceftriaxone and gentamicin were the most effective drugs in general.
Ericsson, Charles D
Risk of travellers' diarrhoea is about 7% in developed countries and 20-50% in the developing world. Options for prevention include education and chemoprophylaxis. Vaccination is a promising but incomplete option. Achieving behaviour modification of food and water choices among tourists is difficult. Bismuth subsalicylate (BSS)-containing compounds are about 62% effective in the prevention of travellers' diarrhoea. Antibiotics are about 84% effective in preventing travellers' diarrhoea. Routine prophylaxis of travellers' diarrhoea, especially with antibiotics, should be discouraged. Oral rehydration is generally important in the treatment of diarrhoea, but travellers' diarrhoea is only infrequently dehydrating in adults. The addition of oral rehydration solutions confers no additional benefit to loperamide in the treatment of travellers' diarrhoea in adults. Presently, the most active of the antibiotics routinely available for treatment are members of the fluoroquinolone group. Antibiotics that are not absorbed such as aztreonam and a rifampicin-like agent, rifaximin, are both effective. The latter might become a therapy of choice once it is routinely available, due to predictably less adverse reactions with a non-absorbed antibiotic. Preliminary results with azithromycin look very promising. Less severe disease can be treated with a variety of non-antibiotic agents (e.g. BSS-containing compounds, loperamide and a calmodulin inhibitor, zaldaride). The combination of an antibiotic and loperamide is superior to treatment with either agent alone in a several studies and is arguably the treatment of choice for distressing travellers' diarrhoea.
Evangelopoulou, Grammato; Kritas, Spyridon; Govaris, Alexander; Burriel, Angeliki R
Salmonella enterica subsp. arizonae was isolated from 13 of 123 slaughtered pigs in central Greece. The samples cultured were feces, ileum tissue, mesenteric lymph nodes, and gallbladder swabs. A total of 74 isolates from 492 samples were identified as Salmonella spp. by use of standard laboratory culture media and two commercial micromethods and by use of a polyvalent slide agglutination test for the detection of O and H antigens. Among them were 19 (25.68%) suspected to be S. enterica subsp. arizonae according to analysis with standard laboratory culture media. Of those, 14 were identified as S. enterica subsp. arizonae by the API 20E (bioMérieux, France) and the Microgen GnA+B-ID (Microgen Bioproducts, Ltd., United Kingdom) identification systems. All the isolates were tested for resistance to 23 antimicrobials. Strains identified as S. enterica subsp. arizonae were resistant to 17 (70.8%) antibiotics. The highest proportions of resistance were observed for sulfamethoxazole-trimethoprim (71.4%), tetracycline (71.4%), ampicillin (64.3%), and amoxicillin (57.1%). Two isolates were resistant to aztreonam (7.1%) and tigecycline (7.1%), used only for the treatment of humans. Thus, pork meat may play a role in the transmission of antibiotic-resistant S. enterica subsp. arizonae to human consumers. This is the first report of S. enterica subsp. arizonae isolation from pigs.
Wang, Jann-Tay; Chen, Pei-Chen; Chang, Shan-Chwen; Shiau, Yih-Ru; Wang, Hui-Ying; Lai, Jui-Fen; Huang, I-Wen; Tan, Mei-Chen; Lauderdale, Tsai-Ling Yang
Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) β-lactam breakpoints on susceptibility rates and on detecting extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues. Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC β-lactamases gene detection by PCR. Univariate and multivariate analyses were performed. Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC β-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these β-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.
Full Text Available Antibiotics are always considered for surgical site infection (SSI in adolescent idiopathic scoliosis (AIS surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily, experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily, and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily. The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG (p < 0.05, respectively. COS reduces the side effects caused by antibiotics (p < 0.05. COS improved biochemical indexes and reduced the levels of interleukin (IL-6 and tumor necrosis factor (TNF alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.
Farzana, K.; Hameed, A.
Among the samples received in pathology laboratory, Pakistan institute of Medical Science, Islamabad, 5069 samples had bacterial growth, among these 2580 (51%) samples were Gram-positive cocci and 1688 were Staphylococcus aureus during a period of two years. Out of these Gram-positive cocci 56% were resistant to penicillin group, 27% were resistant to cephalosporin group, 22% were resistant to aminoglycoside group 15% were resistant to quinolone group and 31% were resistant to other antibiotics (cotrimaxazole, erythromycin, aztreonam, vancomycin, nitrofurantion and meropenam). Antibio-grams of Gram-positive cocci were determined against various antibiotics by disc diffusion method. The rate of resistance to most of the antibiotics such as ampicillin, piperacillin, carbenicillin, penicillin, cephradine, cefotaxime, erythromycin, ceclor, ofloxacin, pefloxacin, ciprofloxacin, cotrimexazole (septran), gentamicin, meropenem, ceftazidime, erythromycin, tobramycin, enoxacin was higher when tested against the isolates collected from pus as compared to those from blood and urine. Antibiotic resistant strains were more prevalent in pus samples than other clinical isolates (blood and urine). The randomly selected 155 strains of Staphylococcus aureus when tested against five groups of antibiotics showed resistance rate against ampicillin (92%), cephradine (92%), cephradine (60%), and gentamicin (58%). However intermediate resistance was found in case of vancomicin (38%), in hospitalized and non-hospitalized patients. (author)
de Melo, Maíra Espíndola Silva; Cabral, Adriane Borges; Maciel, Maria Amélia Vieira; da Silveira, Vera Magalhães; de Souza Lopes, Ana Catarina
The objectives of this study were to determine the distribution of phylogenetic groups among Klebsiella pneumoniae isolates from Recife, Brazil and to assess the relationship between the groups and the isolation sites and resistance profile. Ninety four isolates of K. pneumoniae from hospital or community infections and from normal microbiota were analyzed by gyrA PCR-RFLP, antibiotic susceptibility, and adonitol fermentation. The results revealed the distinction of three phylogenetic groups, as it has also been reported in Europe, showing that these clusters are highly conserved within K. pneumoniae. Group KpI was dominantly represented by hospital and community isolates while groups KpII and KpIII displayed mainly normal microbiota isolates. The resistance to third generation cephalosporins, aztreonam, imipenem, amoxicillin/clavulanic acid, and streptomycin was only observed in KpI. The percentage of resistance was higher in KpI, followed by KpII and KpIII. The differences in the distribution of K. pneumoniae phylogenetic groups observed in this study suggest distinctive clinical and epidemiological characteristics among the three groups, which is important to understand the epidemiology of infections caused by this organism. This is the first study in Brazil on K. pneumoniae isolates from normal microbiota and community infections regarding the distribution of phylogenetic groups based on the gyrA gene.
Yildiz, B.; Kural, N.; Yarar, C.; Ak, I.; Akcar, N.
Objective was to determine the resistance of antibiotics for complicated urinary tract infection (UTI), including urinary tract anomaly (UTA), for empirical antibiotic therapy of complicated UTI. Four hundred and twenty two urine isolates were obtained from 113 patients with recurrent UTI, who used prophylactic antibiotics between February 1999 and November 2004 in the Eskisehir Osmangazi University, Eskisehir, Turkey. Reflux was found to be most important predisposing factor for recurrent UTI (31.9%). Renal scar was detected more in patients with UTA than without UTA (59.2% versus 12.4%, p<0.05). Gram-negative organisms were dominant in patients with and without UTA (91.5% and 79.2%). Enterococci and Candida spp. were more prevalent in children with UTA than without UTA (p<0.001). Isolates were significantly more resistant to ampicillin, trimethoprim-sulfamethoxazole, amikacin, co-amoxiclav, ticarcillin-clvalanate and piperacillin-tazobactam in patients with UTA than without UTA. We found low resistance to ciprofloxacin and nitrofurantoin in UTI with and without UTA. Enterococci spp. was highly resistance to ampicillin and amikacin in patients with UTA. Aztreonam, meropenem and ciprofloxacin seemed to be the best choice for treatment of UTI with UTA due to Escherichia coli and Klebsiella spp. Nitrofurantoin and nalidixic acid may be first choice antibiotics for prophylaxis in UTI with and without UTA. The UTI with UTA caused by Enterococci spp. might not benefit from a combination of amikacin and ampicillin, it could be treated with glycopeptides. (author)
Rodrigo Elisandro Mendes
Full Text Available Nos últimos anos tem sido observada maior incidência de bacilos Gram-negativos resistentes a cefalosporinas de espectro ampliado no ambiente hospitalar, ocasionando, assim, maior uso de betalactâmicos mais potentes, como os carbapenens. A utilização de carbapenens exerce maior pressão seletiva sobre a microbiota hospitalar, o que pode ocasionar aumento da resistência a esses agentes. Entre os mecanismos de resistência a carbapenens mais comumente identificados estão a produção de betalactamases, como, por exemplo, as pertencentes à classe D de Ambler e as que pertencem à classe B de Ambler, ou metalo-beta-lactamases (MbetaL. Essas últimas hidrolisam todos betalactâmicos comercialmente disponíveis, sendo a única exceção o monobactam aztreonam. Desde o início da década de 1990, novos genes que codificam MbetaLs têm sido descritos em microrganismos clinicamente importantes, como Pseudomonas spp., Acinetobacter spp. e membros da família Enterobacteriaceae. O encontro desses microrganismos não-sensíveis a carbapenens pode ser submetido a metodologias fenotípicas para detecção da produção de MbetaL com o intuito de auxiliar a Comissão de Controle de Infecção Hospitalar (CCIH e prevenir a disseminação desses determinantes de resistência, uma vez que genes que codificam MbetaLs estão contidos em estruturas genéticas que propiciam sua mobilidade de forma muito efetiva, sendo então facilmente disseminados.Increase isolation of Gram-negative bacilli resistant to broad-spectrum cephalosporin has been observed during the last few years, thus determining the use of more potent beta-lactams, such as carbapenems. The use of these antimicrobial agents may lead to the emergence of carbapenem resistant Gram-negative bacilli in the nosocomial environment. Carbapenem resistance may be due to the production of Ambler class D beta-lactamase or Ambler class B beta-lactamase, also called metallo-beta-lactamase (MbetaL. Apart from
Análise epidemiológica de isolados clínicos de Pseudomonas aeruginosa provenientes de hospital universitário Epidemiologic analysis of clinical isolates of Pseudomonas aeruginosa from an university hospital
Eduardo José Valença Cordeiro Pires
Full Text Available OBJETIVOS: A Pseudomonas aeruginosa é um patógeno oportunista que tem se destacado quanto à prevalência em casos de infecções hospitalares. Sua ampla resistência aos diversos grupos de antimicrobianos garante a este microrganismo um papel de destaque entre as bactérias mais prevalentes associadas à infecção nosocomial. O objetivo deste estudo foi realizar um levantamento epidemiológico da P. aeruginosa, bem como do seu perfil de susceptibilidade aos antimicrobianos no Hospital das Clínicas da Universidade Federal de Pernambuco. MÉTODOS: Foi realizado um estudo retrospectivo baseado no livro de registro de secreções diversas do laboratório de bacteriologia do Hospital das Clínicas no período compreendido entre janeiro a junho de 2008. Entre os registros, identificamos aqueles que foram positivos para a P. aeruginosa, analisando sua origem e perfil de susceptibilidade aos antimicrobianos utilizados na rotina daquele laboratório. RESULTADOS: As bactérias mais freqüentes, isoladas das secreções diversas, foram P. aeruginosa (26% e S. aureus (25%. Quanto à origem, a P. aeruginosa foi isolada principalmente de infecções respiratórias, pois 33% das amostras positivas para esta bactéria foram provinientes de secreções traqueais e 21% nasais. Os antimicrobianos mais eficazes contra a P. aeruginosa foram: amicacina, imipenem, meropenem e aztreonam. CONCLUSÕES: Estes resultados mostram uma alta prevalência de P. aeruginosa, no Hospital das Clínicas da Universidade Federal de Pernambuco. Apesar de apresentar grande resistência a antimicrobianos mais antigos como as cefalosporinas de primeira e segunda geração, assim como cloranfenicol, em geral, este patógeno demonstrou boa sensibilidade às drogas utilizadas na rotina deste hospital.OBJECTIVES: Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen in hospital infection cases. Its high resistance rates to many antimicrobials has given this
Full Text Available Objective: The aim of this multiple-hospital study was to investigate the prevalence of integrons in multidrug-resistant Acinetobacter baumannii (MDRAB in Eastern China, and characterize the integron-integrase genes, so as to provide evidence for the management and appropriate antibiotic use of MDRAB infections. Methods: A total of 425 clinical isolates of A. baumannii were collected from 16 tertiary hospitals in 11 cities of four provinces (Fujian, Jiangsu, Zhejiang and Shandong from January 2009 to June 2012. The susceptibility of A. baumannii isolates to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, ceftriaxone, cefepime, aztreonam, meropenem, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, sulfamethoxazole/trimenthoprim, minocycline and imipenem was tested, and integrons and their gene cassettes were characterized in these isolates using PCR assay. In addition, integron-positive A. baumannii isolates were genotyped using pulsed-field gel electrophoresis (PFGE assay, and intI1 gene cassette was sequenced. Results: intI1 gene was carried in 69.6% of total A. baumannii isolates, while intI2 and intI3 genes were not detected. The prevalence of resistance to ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, ceftriaxone, cefepime, aztreonam, imipenem, meropenem, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin and sulfamethoxazole/trimenthoprim was significantly higher in integron-positive A. baumannii isolates than in negative isolates (all p values <0.05, while no significant difference was observed in the prevalence of minocycline resistance (p > 0.05. PFGE assay revealed 27 PFGE genotypes and 4 predominant genotypes, P1, P4, P7 and P19. The PFGE genotype P1 contained 13 extensive-drug resistant and 89 non-extensive-drug resistant A. baumannii isolates, while the genotype P4 contained 34 extensive-drug resistant and 67 non-extensive-drug resistant isolates, appearing a significant
Emergencia de la resistencia antibiótica debida a las β-lactamasas de espectro extendido (BLEE: detección, impacto clínico y epidemiología Emergence of antimicrobial resistance to extended-spectrum β-lactamases (ESBL: detection, clinic impact and epidemiology
Full Text Available RESUMEN La rápida emergencia de la resistencia antimicrobiana debida a las BLEE tiene un impacto significativo en la salud pública. En los últimos 24 años ha suscitado un gran interés el conocimiento acerca de las BLEE, esta explosión de publicaciones abarca a todos los continentes y más de 30 países, actualmente es motivo de preocupación y se considera un problema de salud pública. Las BLEE son enzimas que producen los gram negativos y confieren resistencia a las penicilinas, a todas las cefalosporinas y al aztreonam, pero no a los carbapenems ni a las cefamicinas y la mayoría son inhibidas por el acido clavulanico. En general las BLEE son derivadas de TEM-1, TEM-2 y SHV-1, difieren entre si de sus progenitoras por unos escasos aminoácidos por lo que su filogenia es cercana. Son comúnmente encontradas en E.coli, Klebsiella sp, y P.mirabilis, no obstante, existen otras BLEE que difieren filogenéticamente de TEM y SHV, como las CTX-M, las carbapenemasas tipo OXA y las metalo-β-lactamasas VIM e IMP, típicamente encontradas en especies de P. aeruginosa, Serratia sp and Enterobacter sp. La producción de BLEE en los patógenos de importancia clínica es un problema serio en los pacientes hospitalizados debido a las implicaciones clínicas, terapéuticas y económicas. Las técnicas para la detección de las BLEE van de lo simple con aspectos fenotipicos hasta las pruebas complejas moleculares de geno-detección específica. El objetivo de esta revisión es discutir el impacto clínico y epidemiológico de las BLEE más prevalentes así como las técnicas para su detección y su seguimiento nosocomial.ABSTRACT The rapid emerge of antimicrobial resistance dueto ESBL has a significant impact in public health. In the last 24 years, the study of extendedspectrumβ-lactamases (ESBL has created great interest. This has been documented by publications from all continents and more than 30 countries, and the extent of this problem is a public
Actividad "in vitro" de diferentes antibacterianos sobre bacilos gram-negativos no fermentadores, excluidos Pseudomonas aeruginosa y Acinetobacter spp ‘In vitro' activity of different antimicrobial agents on gram-negative nonfermentative bacilli, excluding Pseudomonas aeruginosa and Acinetobacter spp
Full Text Available Los bacilos gram-negativos no fermentadores se encuentran ampliamente distribuidos en el medio ambiente. Además de causar dificultades en la identificación, a menudo presentan una marcada multirresistencia a los antimicrobianos incluyendo aquellos activos frente a Pseudomonas aeruginosa. El objetivo de este trabajo fue evaluar la actividad "in vitro" de diferentes antimicrobianos sobre 177 aislamientos de bacilos gram-negativos no fermentadores (excluidos Pseudomonas aeruginosa y Acinetobacter spp. provenientes de especimenes clínicos. Las concentraciones inhibitorias mínimas (CIM se determinaron por el método de dilución en agar Mueller Hinton frente a los siguientes antibacterianos: ampicilina, piperacilina, piperacilina-tazobactama, sulbactama, cefoperazona, cefoperazona-sulbactama, ceftazidima, cefepima, aztreonam, imipenem, meropenem, colistina, gentamicina, amicacina, trimetoprima-sulfametoxazol (TMS, cloranfenicol, eritromicina, rifampicina, norfloxacina, ciprofloxacina y minociclina. Sobre siete aislamientos: Sphingobacterium multivorum (2, Sphingobacterium spiritivorum (1, Empedobacter brevis (1, Weeksella virosa (1, Bergeyella zoohelcum (1 y Oligella urethralis (1 se ensayó la sensibilidad a amoxicilina-ácido clavulánico y ampicilina-sulbactama y no se determinó la actividad de cefoperazona ni de sulbactama. La multirresistencia fue comúnmente observada en los aislamientos de Stenotrophomonas maltophilia, Burkholderia cepacia, Chryseobacterium spp., Myroides spp., Achromobacter xylosoxidans y Ochrobactrum anthropi. En cambio, Pseudomonas stutzeri, Shewanella putrefaciens-algae, Sphingomonas paucimobilis, Pseudomonas oryzihabitans, Bergeyella zoohelcum, Weeksella virosa y Oligella urethralis, fueron ampliamente sensibles a los antibacterianos ensayados. Debido a la gran variabilidad observada en la sensibilidad a los antimicrobianos en las distintas especies, se hace imprescindible realizar la prueba de sensibilidad a los
Liu, S; Wang, C; Fu, Y X
Objective: To know the drug resistance of Acinetobacter baumannii (AB) in wound of children with traffic injury and its relationship with antibiotic use. Methods: Wound exudate of 226 children with traffic injury admitted to our unit from January 2010 to December 2015 were collected. API bacteria identification panels and fully automatic microbiological identification system were used to identify pathogens. Kirby-Bauer paper disk diffusion method was used to detect the drug resistance of pathogens to 18 antibiotics including amoxycillin/clavulanic acid, piperacillin/tazobactam, and imipenem. The detection situation of pathogen of children's wounds and drug resistance of detected AB to 18 antibiotics in each year were collected. Forty-six AB positive children (2 children excluded) were divided into imipenem-resistant group (IR, n =19) and non imipenem-resistant group (NIR, n =25) according to whether AB was 100% resistant to imipenem. Drug resistance of AB in wounds of children to 18 antibiotics in two groups was compared. The antibiotic use of AB positive children was collected, and the antibiotic use intensity of children in two groups was compared. Data were processed with Fisher's exact test, independent sample t test, and corrected t test. Results: (1) The detection rates of pathogen in wounds of children in 2010-2015 were 95.6% (43/45), 89.8% (53/59), 81.3% (148/182), 81.1% (107/132), 81.6% (120/147), and 77.5% (62/80), respectively, showing a trend of decreasing year by year. A total of 665 strains and 75 pathogens were detected, and the top 5 pathogens with detection rate from high to low were AB, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermidis, and Escherichia coli, respectively. (2) Drug resistance rates of AB to amoxycillin/clavulanic acid, cefazolin, aztreonam, and piperacillin were all 100%, while AB was 100% sensitive to polymyxin, and the total drug resistance rates of AB to the other 13 antibiotics were all above 50%. The
Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W
Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.
Full Text Available The emergence and spread of carbapenemase-producing Enterobacteriaceae (CPE represent a major public health concern because these bacteria are usually extensively resistant to most antibiotics. In order to evaluate their dissemination in Quebec, a surveillance program was introduced in 2010. We report the molecular and epidemiological profiles of CPE isolates collected. Between August 2010 and December 2012, a total of 742 non-duplicate isolates non-susceptible to carbapenems were analysed. AmpC β-lactamase and metallo-β-lactamase production were detected by Etest and carbapenemase production by the modified Hodge test (MHT. Antibiotic susceptibility profiles were determined using broth microdilution or Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC strains was analyzed by pulsed-field gel electrophoresis (PFGE. The presence of genes encoding carbapenemases as well as other β-lactamases was detected using PCR. Of the 742 isolates tested, 169 (22.8% were CPE. Of these 169 isolates, 151 (89.3% harboured a blaKPC gene while the remaining isolates carried blaSME (n = 9, blaOXA-48 (n = 5, blaNDM (n = 3, and blaNMC (n = 1 genes. Among the 93 KPC strains presenting with a unique pattern (unique PFGE pattern and/or unique antibiotics susceptibility profile, 99% were resistant to ertapenem, 95% to imipenem, 87% to meropenem, 97% to aztreonam, 31% to colistin and 2% to tigecycline. In 19 patients, 2 to 5 KPC strains from different species or with a different PFGE pattern were isolated. CPE strains were present in the province of Quebec with the majority of strains harbouring KPC. Alternately, SME, OXA-48 and NMC containing strains were rarely found.
Zhong, Xue-Shan; Ge, Jing; Chen, Shao-Wei; Xiong, Yi-Quan; Zheng, Xue-Yan; Qiu, Min; Huo, Shu-Ting; Chen, Qing
To investigate antimicrobial resistance of Klebsiella pneumoniae and Pseudomonas aeruginosa isolates in fecal samples from rat-like animals. Rat-like animals were captured using cages around a hospital and the neighboring residential area between March and October, 2015. K. pneumoniae and P. aeruginosa were isolated from the fecal samples of the captured animals. Antimicrobial susceptibility test was performed according to the guidelines of Clinical and Laboratory Standards Institute (2014). A total of 329 rat-like animals were captured, including 205 Suncus murinus, 111 Rattus norvegicus, 5 Rattus flavipectus and 8 Mus musculus. The positivity rates of K. pneumoniae and P. aeruginosa were 78.4% and 34.7% in the fecal samples from the captured animals, respectively. K. pneumoniae isolates from Suncus murinus showed a high resistance to ampicillin, cephazolin, nitrofurantoin, piperacillin and cefotaxime (with resistance rates of 100%, 51.2%, 44.2%, 37.2%, and 23.3%, respectively), and K. pneumoniae isolates from Rattus spp. showed a similar drug-resistance profile. The prevalence rates of multidrug resistance and ESBLs were 40.9% and 10.7%, respectively. P. aeruginosa from both Suncus murinus and Rattus spp. exhibited the highest resistance rates to aztreonam (12.4% and 16.0%, respectively), followed by penicillins and fluoroquinolones. P. aeruginosa isolates were susceptible to cephems, aminoglycosides and carbapenems (with resistance rates below 5%). K. pneumoniae and P. aeruginosa isolated from rat-like animals showed drug-resistance profiles similar to those of the strains isolated from clinical patients, suggesting that the possible transmission of K. pneumoniae and P. aeruginosa between rat-like animals and human beings.
Jacoby, G A; Carreras, I
Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases. PMID:2193623
García-Tello, A; Gimbernat, H; Redondo, C; Arana, D M; Cacho, J; Angulo, J C
Beta-lactamases are bacterial enzymes that protect microorganisms from the lethal effects of β-lactam antibiotics. The production of beta-lactamases is the most important mechanism of resistance to these antibiotics, especially in Gram-negative bacteria. Review the magnitude of the problem of extended-spectrum beta-lactamases (ESBL) in the urological setting and present the fundamental action guidelines on the issue, the main risk factors and the prevention strategies. A structured search strategy for patient, problem, intervention, comparison and result was conducted in the PubMed-Medline database to identify the most relevant studies related to the management of patients with urinary tract infection by ESBL-producing microorganisms. We also present a caseload analysis of our center on this issue. ESBL are found in Enterobacteria, mainly Klebsiella sp. and Escherichia coli and are characterized by their hydrolytic ability compared with beta-lactam antibiotics, which entails resistance to penicillin, cephalosporin and aztreonam. They are also associated with resistance to other antibiotics. There is a high risk of infection and colonization by ESBL producers in patients with prolonged hospital stays or who required invasive devices. The prior use of antibiotics and stays in residential care are also risk factors. Prevention programs should focus on preventing nosocomial infection. It is essential that a restrictive policy on the use of antibiotics be implemented. The therapy of choice for severe infections is focused on carbapenems, although their indiscriminate use should be avoided. In uncomplicated lower urinary tract infections, fosfomycin and nitrofurantoin are the best treatment alternatives. ESBL-producing strains constitute a true global health problem. Prevention strategies should focus on nosocomial infection. We should not forget, however, that the appearance of these pathogens in community-acquired infections is increasingly frequent. Therapeutic
Mangat, Chand S; Boyd, David; Janecko, Nicol; Martz, Sarah-Lynn; Desruisseau, Andrea; Carpenter, Michael; Reid-Smith, Richard J; Mulvey, Michael R
One of the core goals of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) is to monitor major meat commodities for antimicrobial resistance. Targeted studies with methodologies based on core surveillance protocols are used to examine other foods, e.g., seafood, for antimicrobial resistance to detect resistances of concern to public health. Here we report the discovery of a novel Ambler class A carbapenemase that was identified in a nontoxigenic strain of Vibrio cholerae (N14-02106) isolated from shrimp that was sold for human consumption in Canada. V. cholerae N14-02106 was resistant to penicillins, carbapenems, and monobactam antibiotics; however, PCR did not detect common β-lactamases. Bioinformatic analysis of the whole-genome sequence of V. cholerae N14-02106 revealed on the large chromosome a novel carbapenemase (referred to here as VCC-1, for Vibrio cholerae carbapenemase 1) with sequence similarity to class A enzymes. Two copies of blaVCC-1 separated and flanked by ISVch9 (i.e., 3 copies of ISVch9) were found in an acquired 8.5-kb region inserted into a VrgG family protein gene. Cloned blaVCC-1 conferred a β-lactam resistance profile similar to that in V. cholerae N14-02106 when it was transformed into a susceptible laboratory strain of Escherichia coli. Purified VCC-1 was found to hydrolyze penicillins, 1st-generation cephalosporins, aztreonam, and carbapenems, whereas 2nd- and 3rd-generation cephalosporins were poor substrates. Using nitrocefin as a reporter substrate, VCC-1 was moderately inhibited by clavulanic acid and tazobactam but not EDTA. In this report, we present the discovery of a novel class A carbapenemase from the food supply. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Al-Agamy, Mohamed H; Jeannot, Katy; El-Mahdy, Taghrid S; Shibl, Atef M; Kattan, Wael; Plésiat, Patrick; Courvalin, Patrice
This study was conducted to investigate the molecular epidemiology of resistance in Acinetobacter baumannii isolates collected at a hospital in Riyadh, Saudi Arabia, from January through December 2010. Twenty-seven A. baumannii were highly resistant (MIC 90 > 256 μg/ml) to ceftazidime, cefepime, and aztreonam. Imipenem resistance was seen in 24 isolates, of which 18 had an minimum inhibitory concentration (MIC) >32 μg/mL. Ciprofloxacin, gentamicin, and amikacin resistance was found in 93%, 52%, and 37% of all the isolates, respectively. Moreover, 8 (30%) isolates showed colistin resistance, and 15 (56%) were found to have MICs ≥4 μg/mL for tigecycline. The frequency of ADC, GES-1, GES-11, and GES-5 were 96.3% (n = 26), 18.5% (n = 5), 11% (n = 3), and 3.7% (n = 1), respectively. OXA-23 was found in 63% (n = 17) of the isolates; ISAba1 was found upstream of OXA-23 in 16. OXA-24/40 was detected in only one strain. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) analysis revealed that the 27 strains were distributed in 8 sequence types (STs) and 16 clonal pulsotypes (A-P). Five singleton STs were identified, including ST15 and ST113-ST116. The emergence of multidrug-resistant A. baumannii is becoming a major concern in Saudi Arabia. Metallo-β-lactamases have no role in carbapenem resistance in this collection. The spread of OXA-23 in our strains occurred across different STs and pulsotypes, unlike what has been observed in many other countries. PFGE typing was more discriminatory than MLST. The high frequency of colistin and tigecycline resistance found in the isolates calls for continuous monitoring. This study describes the first identification of GES-5 conferring carbapenem resistance in A. baumannii.
Full Text Available The aim of this study was to investigate the phylogenetic background and to assess hlyD (involved in the secretion of haemolysin A and intll (encoding a class 1 integrase in Escherichia coli isolates derived from urinary and fecal specimens. A total of 200 E. coli isolates was collected from patients presenting with urinary tract infection (UTI during September 2009 to September 2010 and screened for hlyD and intll genes by polymerase chain reaction (PCR. Phylogenetic analysis showed that E. coli is composed of four main phylogenetic groups (A, B1, B2 and D and that uropathogenic E. coli (UPEC isolates mainly belong to groups B2 (54% and D (34% whereas group A (44% and D (26% are predominant among commensal E. coli isolates. In this study, hlyD was present in 26% of UPEC and 2% of commensal E. coli isolates. However, hemolytic activity was detected for 42% of UPEC and 6% of commensal E. coli isolates (p < 0.05. intll gene was more frequently expressed in UPEC (24% in comparison with commensal E. coli isolates (12%. Resistance to aztreonam, co-trimoxazole and cefpodoxime were frequently found among UPEC isolates whereas commensal E. coli isolates were commonly resistant to co-trimoxazole, nalidixic acid and cefotaxime. Concluding, a considerable difference between UPEC and commensal E. coli isolates was observed regarding their phylogenetic groups, presence of class 1 integron and hlyD gene, hemolysin activity and resistance pattern. The detection of class 1 integrons and hlyD gene was higher among UPEC compared with commensal E. coli isolates. These findings may contribute for a better understanding of the factors involved in the pathogenesis of UPEC.
Karampatakis, Theodoros; Geladari, Anastasia; Politi, Lida; Antachopoulos, Charalampos; Iosifidis, Elias; Tsiatsiou, Olga; Karyoti, Aggeliki; Papanikolaou, Vasileios; Tsakris, Athanassios; Roilides, Emmanuel
Solid-organ transplant recipients may display high rates of colonization and/or infection by multidrug-resistant bacteria. We analysed and compared the phenotypic and genotypic diversity of carbapenem-resistant (CR) strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii isolated from patients in the Solid Organ Transplantation department of our hospital. Between March 2012 and August 2013, 56 CR strains from various biological fluids underwent antimicrobial susceptibility testing with VITEK 2, molecular analysis by PCR amplification and genotypic analysis with pulsed-field gel electrophoresis (PFGE). They were clustered according to antimicrobial drug susceptibility and genotypic profiles. Diversity analyses were performed by calculating Simpson's diversity index and applying computed rarefaction curves.Results/Key findings. Among K. pneumoniae, KP-producers predominated (57.1 %). VIM and OXA-23 carbapenemases prevailed among P. aeruginosa and A. baumannii (89.4 and 88.9 %, respectively). KPC-producing K. pneumoniae and OXA-23 A. baumannii were assigned in single PFGE pulsotypes. VIM-producing P. aeruginosa generated multiple pulsotypes. CR K. pneumoniae strains displayed phenotypic diversity in tigecycline, colistin (CS), amikacin (AMK), gentamicin (GEN) and co-trimoxazole (SXT) (16 clusters); P. aeruginosa displayed phenotypic diversity in cefepime (FEP), ceftazidime, aztreonam, piperacillin, piperacillin-tazobactam, AMK, GEN and CS (9 clusters); and A. baumannii displayed phenotypic diversity in AMK, GEN, SXT, FEP, tobramycin and rifampicin (8 clusters). The Simpson diversity indices for the interpretative phenotype and PFGE analysis were 0.89 and 0.6, respectively, for K. pneumoniae strains (P<0.001); 0.77 and 0.6 for P. aeruginosa (P=0.22); and 0.86 and 0.19 for A. baumannii (P=0.004). The presence of different antimicrobial susceptibility profiles does not preclude the possibility that two CR K. pneumoniae or A. baumannii
Dias, Rubens Clayton da Silva; Borges-Neto, Armando Alves; Ferraiuoli, Giovanna Ianini D’Almeida; de-Oliveira, Márcia P.; Riley, Lee W.; Moreira, Beatriz Meurer
Production of extended-spectrum β-lactamases (ESBL) has been reported in virtually all species of Enterobacteriaceae, which greatly complicates the therapy of infections caused by these organisms. However, the frequency of isolates producing AmpC β-lactamases, especially plasmid mediated AmpC (pAmpC), is largely unknown. These β-lactamases confer resistance to extended spectrum cephalosporins and aztreonam, a multidrug-resistant (MDR) profile. The aim of the present study was to determine the occurrence of ESBL and pAmpC β-lactamases in a hospital where MDR enterobacterial isolates recently emerged. A total of 123 consecutive enterobacterial isolates obtained from 112 patients at a university hospital in Rio de Janeiro, Brazil during March-June 2001 were included in the study. ESBL was detected by the addition of clavulanate to cephalosporin containing disks and by double diffusion. AmpC production was evaluated by a modified tridimensional test and a modified Hodge test. The presence of plasmid-mediated ampC β-lactamase genes was evaluated by multiplex-PCR. Sixty-five (53%) of 123 enterobacterial isolates were MDR, obtained from 56 patients. ESBL production was detected in 35 isolates; 5 clonal E. coli isolates exhibited high levels of chromosomal AmpC and ESBL production. However, no isolates contained pAmpC genes. Infection or colonization by MDR enterobacteria was not associated with any predominant resistant clones. A large proportion of hospital infections caused by ESBL-producing enterobacteria identified during the study period were due to sporadic infections rather than undetected outbreaks. This observation emphasizes the need to improve our detection methods for ESBL- and AmpC-producing organisms in hospitals where extended-spectrum cephalosporins are in wide use. PMID:17900845
Radhouani, H; Poeta, P; Igrejas, G; Gonçalves, A; Vinué, L; Torres, C
Fifty-three faecal samples from yellow-legged gulls (Larus cachinnans) at the Berlengas nature reserve in Portugal were cultured on Levine agar plates not supplemented with antimicrobial agents, and one Escherichia coli colony was isolated and identified from each sample. The percentages of resistant isolates for each of the drugs were ampicillin (43.4 per cent), tetracycline (39.6 per cent), nalidixic acid (34.0 per cent), streptomycin (32.1 per cent), trimethoprim-sulfamethoxazole (SXT) (26.4 per cent), ciprofloxacin (18.9 per cent), chloramphenicol (18.9 per cent), gentamicin (7.5 per cent), tobramycin (7.5 per cent) amikacin (5.7 per cent) and amoxicillin-clavulanic acid (1.9 per cent). All the isolates were susceptible to cefoxitin, ceftazidime, cefotaxime, aztreonam and imipenem. The following resistance genes were detected: bla(TEM) (17 of 23 ampicillin-resistant isolates), tet(A) and/or tet(B) (18 of 21 tetracycline-resistant isolates), aadA (12 of 17 streptomycin-resistant isolates), cmlA (all chloramphenicol-resistant isolates), aac(3)-II with or without aac(3)-IV (all four gentamicin-resistant isolates), and sul1 and/or sul2 and/or sul3 (all 14 SXT-resistant isolates). The intI1 gene was detected in 10 of 14 SXT-resistant isolates, and three of them also contained class 2 integrons; four different gene cassette arrangements were identified among class 1 integrons (aadA, dfrA1+aadA1, dfrA12+orfF+aadA2 and sat+psp+aadA2) and one among the class 2 integrons (dfrA1+sat+aadA1). Ninety per cent of the isolates were included in the A or B1 phylogenetic groups.
Full Text Available Abstract Background The purpose of this study was to investigate the prevalence of MRSA in herds of fattening pigs in different regions of Germany, and to determine factors associated with the occurrence of this pathogen. For this purpose pooled dust samples were collected, and a questionnaire covered information regarding herd characteristics and management practices. Samples were pre-enriched in high-salt medium followed by selective enrichment containing cefoxitin/aztreonam, and culturing. Presumptive colonies were confirmed by multiplex-PCR targeting nuc-, mecA- and 16S rRNA-genes. Isolates were spa- and SCCmec-, and in selected cases, multilocus sequence-typed. Susceptibilities to 13 antimicrobials were determined by broth microdilution. Statistical analysis was carried out using backward stepwise logistic regression to calculate odds ratios with the MRSA test result as the outcome and herd characteristics as categorical covariates. Results Overall, 152 of 290 (52% fattening pig farms tested positive for MRSA. The prevalence in the east, north- and south-west of Germany ranged from 39 to 59%. t011 (66% and t034 (23% were the most commonly identified spa-types, and 85% of isolates carried SCCmec Type V. Identified spa-types were all associated with clonal complex CC398. Susceptibility testing revealed that all isolates were resistant to tetracycline. High resistance rates were also found for sulfamethoxazole/trimethoprim (40%, and quinupristin/dalfopristin (32%. In addition, 83% of strains displayed multidrug resistant (> 3 substance classes phenotypes. Logistic regression revealed herd size (large farms OR: 5.4; CI: 2.7-11.2; p Conclusions MRSA CC398 is widely distributed among herds of fattening pigs in Germany. Farm management plays a crucial role in the dissemination of MRSA with herd size, and production type representing potential major indicators.
Alt, Katja; Fetsch, Alexandra; Schroeter, Andreas; Guerra, Beatriz; Hammerl, Jens A; Hertwig, Stefan; Senkov, Natalja; Geinets, Anna; Mueller-Graf, Christine; Braeunig, Juliane; Kaesbohrer, Annemarie; Appel, Bernd; Hensel, Andreas; Tenhagen, Bernd-Alois
The purpose of this study was to investigate the prevalence of MRSA in herds of fattening pigs in different regions of Germany, and to determine factors associated with the occurrence of this pathogen. For this purpose pooled dust samples were collected, and a questionnaire covered information regarding herd characteristics and management practices. Samples were pre-enriched in high-salt medium followed by selective enrichment containing cefoxitin/aztreonam, and culturing. Presumptive colonies were confirmed by multiplex-PCR targeting nuc-, mecA- and 16S rRNA-genes. Isolates were spa- and SCCmec-, and in selected cases, multilocus sequence-typed. Susceptibilities to 13 antimicrobials were determined by broth microdilution. Statistical analysis was carried out using backward stepwise logistic regression to calculate odds ratios with the MRSA test result as the outcome and herd characteristics as categorical covariates. Overall, 152 of 290 (52%) fattening pig farms tested positive for MRSA. The prevalence in the east, north- and south-west of Germany ranged from 39 to 59%.t011 (66%) and t034 (23%) were the most commonly identified spa-types, and 85% of isolates carried SCCmec Type V. Identified spa-types were all associated with clonal complex CC398. Susceptibility testing revealed that all isolates were resistant to tetracycline. High resistance rates were also found for sulfamethoxazole/trimethoprim (40%), and quinupristin/dalfopristin (32%). In addition, 83% of strains displayed multidrug resistant (> 3 substance classes) phenotypes.Logistic regression revealed herd size (large farms OR: 5.4; CI: 2.7-11.2; p pig operations. MRSA CC398 is widely distributed among herds of fattening pigs in Germany. Farm management plays a crucial role in the dissemination of MRSA with herd size, and production type representing potential major indicators.
Hamid, M.H.; Maqbool, S.
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)
Ansari, M.; Saad, N.
Objective:To differentiate between Ambler class A, B and D of carbapenemase-producing Enterobacteriaceae by using simple phenotypic methods that can be carried out in the laboratory without requiring any specialised techniques. Study Design:Cross-sectional study. Place and Duration of Study:Microbiology Department, Army Medical College, NUST, Islamabad, from November 2015 to November 2016. Methodology: Clinical specimens were subjected to identification of Enterobacteriaceae by colony morphology and API 20 E. Carbapenem resistance was detected by applying meropenem disc (10 mu g) by disc diffusion method according to CLSI (Clinical Laboratory Standard Institute) criteria. Carbapenemase production among Enterobacteriaceaewas detected by Modified Hodge test. Phenotypic methods, Phenylboronic acid (for Class A KPC producing Enterobacteriaceae) and EDTA inhibition tests (for Class B MBL producing Entrobacteriaceae) were applied. Presence of OXA 48 was detected by phenotypic method using imipenem 10 mu g, EDTA and PBA discs. Antibiotic susceptibility was determined by Kirby-Bauer disc diffusion method. Results:Forty-three out of 45 (95.45%) were carbapenemase producers. Thirty-eight out of 43 (88.3%) were KPC producers and 4 out of 43 (11.62%) were MBL producers. All KPC producers were Klebsiella pneumoniae. Among five MBL producers, one each (20%) was Enterobacter cloacae and Escherichia coli and 3 (60%) were Klebsiella pneumoniae. All MBL producers were resistant to aztreonam and amoxicillin/clavulanate. Two of the KPC producing Klebsiella pneumoniaewere pan-drug resistant (resistant to colistin and tigecycline). Two were non-carbapenemase producers. Conclusion:Enterobacteriaceaestrains producing KPC-type carbapenemase were the most prevalent (88.3%) in the studied healthcare setup. (author)
Mai M. Zafer
Full Text Available This study was designed to investigate the prevalence of metallo-β-lactamases (MBL and extended-spectrum β-lactamases (ESBL in P. aeruginosa isolates collected from two different hospitals in Cairo, Egypt. Antibiotic susceptibility testing and phenotypic screening for ESBLs and MBLs were performed on 122 P. aeruginosa isolates collected in the period from January 2011 to March 2012. MICs were determined. ESBLs and MBLs genes were sought by PCR. The resistant rate to imipenem was 39.34%. The resistance rates for P. aeruginosa to cefuroxime, cefoperazone, ceftazidime, aztreonam, and piperacillin/tazobactam were 87.7%, 80.3%, 60.6%, 45.1%, and 25.4%, respectively. Out of 122 P. aeruginosa, 27% and 7.4% were MBL and ESBL, respectively. The prevalence of blaVIM-2, blaOXA-10-, blaVEB-1, blaNDM-, and blaIMP-1-like genes were found in 58.3%, 41.7%, 10.4%, 4.2%, and 2.1%, respectively. GIM-, SPM-, SIM-, and OXA-2-like genes were not detected in this study. OXA-10-like gene was concomitant with VIM-2 and/or VEB. Twelve isolates harbored both OXA-10 and VIM-2; two isolates carried both OXA-10 and VEB. Only one strain contained OXA-10, VIM-2, and VEB. In conclusion, blaVIM-2- and blaOXA-10-like genes were the most prevalent genes in P. aeruginosa in Egypt. To our knowledge, this is the first report of blaVIM-2, blaIMP-1, blaNDM, and blaOXA-10 in P. aeruginosa in Egypt.
Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D.
Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation
Full Text Available Abstract Background Extended spectrum ß-lactamases (ESBLs represent a major group of lactamases responsible for resistance, mostly produced by gram-negative bacteria, to newer generations of ß-lactam drugs currently being identified in large numbers worldwide. The present study was undertaken to see the frequency of ESBL producing Pseudomonas spp. isolated from six hundred clinical specimens (wound, pus, aural, urine, sputum, throat and other swabs collected over a period of three years from two tertiary care hospitals in Bangladesh. Findings Aerobic bacterial culture was performed on aseptically collected swabs and only growth of Pseudomonas was considered for further species identification and ESBL production along with serotyping of Pseudomonas aeruginosa. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer agar diffusion method and ESBL production was detected on Mueller Hinton agar by double-disk synergy technique using Amoxicillin-Clavulanic acid with Ceftazidime, Cefotaxime, Ceftriaxone and Aztreonam. Culture yielded 120 Pseudomonas spp. and 82 of them were biochemically characterized for species. Pseudomonas aeruginosa was found to be the predominant (90.2% species. Of 82 isolates tested for ESBL, 31 (37.8% were ESBL positive with 29 (93.5% as Pseudomonas aeruginosa, the remaining 2 (6.5% were Stenotrophomonas maltophilia and Ralstonia pickettii. Antibiogram revealed Imipenem as the most effective drug (93.3% among all antimicrobials used against Pseudomonas spp. followed by Aminoglycosides (63.7%. Conclusion ESBL producing Pseudomonas spp. was found to be a frequent isolate from two tertiary care hospitals in Bangladesh, showing limited susceptibility to antimicrobials and decreased susceptibility to Imipenem in particular, which is a matter of great concern.
Olusolabomi J Idowu
Full Text Available Background: Extended-spectrum beta-lactamase (ESBL-producing Gram-negative bacteria are emerging and impacting significantly on the management of patients and hospital costs. Besides, they are not being routinely sought after in diagnostic laboratories thus contributing to treatment failure. Materials and Methods: Bacterial isolates from wounds of 45 patients were identified using commercial identification kits and antibiotic susceptibility was evaluated by the Bauer-Kirby method. Screening and phenotypic confirmation of ESBL production were done as prescribed by the Clinical and Laboratory Standards Institute. The conjugation experiment was performed by the mating assay in broth between the ESBL producers and E. coli ATCC 25922 as the recipient. Results: Out of 102 Gram-negative bacteria isolated, 36 were positive for ESBL mainly of the Enterobacteriaceae family (33 and the rest were oxidase-positive bacilli (3. The predominant bacteria were Klebsiella spp. and E. coli. Others were Serratia rubidae, Citrobacter freundii, Morganella morgannii, Proteus spp., Providencia stuartii, and Enterobacter spp. There was a significant association between treatment with third-generation cephalosporins (3GCs and isolation of ESBLs ( p=0.0020 . The ESBL producers were multiply resistant and moderately sensitive to colistin. The conjugation experiment showed that the ESBL gene was transferred horizontally and tetracycline, cotrimoxazole, nitrofurantoin, gentamicin, and aztreonam resistance genes were co-transferred. No mortality was recorded but the mean length of stay in the hospital was 82 days. Conclusion: The development and spread of ESBL among Gram-negative bacteria and possible horizontal transfer calls for concern, especially in view of treatment failure, high treatment cost, and consequent discomfort to patients.
de Oliveira, Daniele V; Van Der Sand, Sueli T
Some bacteria from the Enterobacteriaceae family are showing a significant capability to disseminate β-lactams resistance mechanisms among them, and these same mechanisms can be carried out from the hospital environment to superficial water. The aim of this study was to evaluate different phenotypic methods for the detection β-lactamases production by enterobacteria isolated from the anthropogenic environment: hospital wastewater and from a stream that cross the city of Porto Alegre. The applied tests were the modified Hodge test (MHT) and phenotypic tests with the following inhibitors: carbapenemase-phenylboronic acid (APB), metallo-β-lactamase-EDTA, AmpC β-lactamase-cloxacillin, and the confirmatory test for extended-spectrum β-lactamase (ESBL)-clavulanic acid. For this evaluation, 131 isolates were initially subjected to antibiogram using the following antimicrobials: cefotaxime (30 µg), cefpodoxime (10 μg), ceftazidime (30 µg), ertapenem (10 μg), meropenem (10 μg), and aztreonam (30 μg). After this first screening, 62 isolates showed a profile resistance for at least one antimicrobial. These isolates were subjected to all phenotypic tests. Of those, 40 isolates were positive for at least one phenotypic test. In MHT test, one isolate was positive and five were with inconclusive results. The results achieved with the inhibitors are as follows: APB 25/40 positive strains; EDTA 8/40 positive strains; and with CLOXA 2/40 positive strains. ESBL production was observed for 34/40 strains. This assessment shows a high level of bacteria which can produce enzymes that inactivate β-lactams present in the different environment like the stream waters and from the hospital settings.
Cristina Letícia Rugini
Full Text Available Abstract: INTRODUCTION: Nosocomial infections are closely associated with antimicrobial drug resistance. One of the most important mechanisms of resistance to β-lactam antibiotics is the production of extended spectrum β-lactamases (ESBLs. The objective of the present study was to evaluate the prevalence and antimicrobial susceptibility profile of ESBL-producing strains and to assess the evolution of antimicrobial drug resistance between 2007 and 2013 at the Hospital São Vicente de Paulo, Passo Fundo, State of Rio Grande do Sul, Brazil. METHODS: We conducted a descriptive, observational, cross-sectional study. Bacterial culture was performed from January to December 2013. The antimicrobial susceptibility profile of these cultures was determined using the disk diffusion method. Phenotypic screening for ESBL production was performed using the disk approximation method. RESULTS : We analyzed a total of 19,112 cultures, 11.5% of which were positive for Enterobacteriaceae. Of these, 30.3% of the isolates were positive for ESBL production, and the most prevalent species was Klebsiella sp. (37.5%. Over 95% of these isolates showed reduced susceptibility to all cephalosporins, aztreonam, and amoxicillin/clavulanic acid. The isolates also showed high sensitivity to the following antimicrobials: amikacin, meropenem, and piperacillin/tazobactam. Overall, the resistance rates among ESBL-producing Enterobacteriaceae decreased from 2007 to 2013. CONCLUSIONS : In our hospital, the increased sensitivity to certain antimicrobial agents seems to be directly related to the implementation of improvements in the methods to prevent and control nosocomial infections in addition to the natural development of other resistance mechanisms.
Broseta Rico, Enrique; Jiménez Cruz, Juan Fernando
To review the topic of urinary tract infections (UTI) during pregnancy and menopause. UTI during pregnancy and menopause have great relevance in the field of urologic infections; during pregnancy because of the particularities involved in its diagnosis and treatment and potential consequences to the fetus and mother; menopausal UTI because this group of women is numerous and represents a growing section of the general population pyramid, due to the aging of population in developed countries associated with longer life expectancies and grater demand for quality of life. We performed a bibliographic review combined with our personal experience. During pregnancy there are several functional and anatomical changes that condition not only a higher risk of UTI, but also an additional treatment difficulty due to antimicrobial pharmacokinetics alterations and potential damage to the fetus. Despite efforts to find an easy, fast and reliable test for bacteriuria detection, urine culture continues to be the first diagnostic test for its detection and follow up during pregnancy. Penicillin derivates and cephalosporins continue to be the first choice because their lack of adverse effects on either fetus or mother. Alternative options like phosphomicin and aztreonam although they show low toxicity there is need for more studies supporting their suitability for the treatment of pregnancy UTIs. Menopausal female UTI have their different features from those in younger women. Hormonal alterations derived from gonadal atrophy associate functional changes in the vaginal ecosystem, making it prone to enterobacteriaceae colonization as a first step up to the urinary tract. This associated with genitourinary tract anatomical alterations inherent t aging make UTI extraordinary prevalent in this growing segment of population. Treatment lines focus on hormonal alteration correction and proper antimicrobial prophylaxis and vaccines in a close future. UTIs during pregnancy and menopause have
Mateus-Vargas, Rafael H; Atanassova, Viktoria; Reich, Felix; Klein, Günter
The increasing number of antimicrobial resistant Enterobacteriaceae both in veterinary and human medicine, the dissemination of these bacteria in several environments and their possible repercussions on human health is causing concern. Game meat is usually seen as free of antimicrobial resistant bacteria. The objective of this study was to evaluate the current antimicrobial susceptibility status in generic Escherichia coli isolated from packed frozen game meat from a game handling establishment in Germany. A total of 229 E. coli isolates were obtained from cuts of red deer, roe deer and wild boar. The susceptibility to 12 antimicrobial agents was evaluated by a broth microdilution method according to ISO 20776-1:2006. Minimal Inhibitory Concentration (MIC) values were compared to breakpoints and cut-off values published by the EUCAST. Isolates showing MICs above the reference values were further studied for associated resistance determinants and phylogrouping by PCR. Overall, 16 E. coli isolates (7.0%) showed resistance (microbiological or clinical) to at least one antimicrobial agent tested. Clinical resistance was recorded to ampicillin (5/229) and chloramphenicol (4/229), whereas the MIC of 9 isolates exceeded the epidemiological cut-off value for doxycycline. One of the ampicillin-resistant isolates showed resistance to the β-lactam antibiotic derivatives tested, cephalosporines and aztreonam. Three of 9 non-wild-type isolates for doxycycline were positive for tet (B) genes. The ß-lactam-resistant isolate was found to harbour bla CTX-M-1 gene. These data show a low prevalence of resistant E. coli in packed game meat compared to studies on conventional meat. Although isolates obtained in this study may also be originating from the processing environment and not necessarily from animals, based on our results, it is important to monitor the development of antimicrobial resistance in game animals and products in order to identify future threats for the
de Boer, E; Zwartkruis-Nahuis, J T M; Wit, B; Huijsdens, X W; de Neeling, A J; Bosch, T; van Oosterom, R A A; Vila, A; Heuvelink, A E
Recently the isolation of methicillin-resistant Staphylococcus aureus (MRSA) strains from several food-producing animals has been reported. During slaughtering of MRSA-positive animals, contamination of carcasses with MRSA may occur and consequently the meat of these animals may get contaminated. The aim of this study was to estimate the prevalence of MRSA in raw meat samples from the retail trade. Samples of raw beef, pork, veal, lamb/mutton, chicken, turkey, fowl and game were collected from the retail trade. A detection method including a two-step enrichment in Mueller-Hinton broth+6.5% NaCl and phenol red mannitol broth containing ceftizoxime and aztreonam, followed by isolation on MRSA ID agar (bioMérieux) was evaluated and subsequently applied for the detection of MRSA in samples of raw meats. MRSA strains were isolated from 264 (11.9%) of 2217 samples analyzed. Isolation percentages for the meat species were: beef (10.6%), veal (15.2%), lamb and mutton (6.2%), pork (10.7%), chicken (16.0%), turkey (35.3%), fowl (3.4%) and game (2.2%). The majority (85%) of the isolated strains belonged to spa-types of pulsed-field gel electrophoresis (PFGE) non-typeable (NT)-MRSA, corresponding to the multilocus sequence type ST398, a type also recently isolated in the Netherlands from pigs. However, a smaller part of these strains were found to be of other ST's, possibly of human origin. Further studies are needed to elucidate transmission routes of MRSA in relation to meat and other foods and to provide the tools for preventing the spread of MRSA. At present the high prevalence of MRSA in meat has not been shown to contribute significantly to the dissemination of MRSA to humans and the possible health hazard for consumers of the presence of MRSA in foods should be further elucidated.
Full Text Available E. coli O157:H7 y Salmonella spp., son bacterias de distribución mundial causantes de enfermedades intestinales queafectan tanto al hombre como a LOS animales. ESTE estudio tuvo como objetivo determinar la presencia y frecuenciade aparición de E. coli O157:H7 y Salmonella spp., en los diferentes sistemas de producción porcina que se empleanen el departamento de Córdoba. Se realizó un estudio de corte descriptivo prospectivo, con un muestreo al azar enlos sistemas de explotación porcina intensiva y extensiva. Se procesaron 500 muestras de materia fecal de porcinos,250 provenientes del sistema extensivo y 250 del sistema intensivo. Para la detección E. coli y Salmonella spp., sellevaron a cabo procedimientos estándares microbiológicos. Los resultados mostraron una frecuencia de aparición deSalmonella spp., del 1%, el 0.2% en el sistema intensivo y el 0.8% en el sistema extensivo; no se aisló Escherichia coliO157:H7. Los resultados de resistencia y sensibilidad a los antibióticos en las cepas aisladas de Salmonella spp.,mostraron una sensibilidad del 100% al trimetoprim sulfametozasol, a la amikacina, al ceftriaxona, a la ciprofloxacina,a la gentamicina y al aztreonam y un 20% a la ampicilina y al sulbactam. Se concluye que la frecuencia de apariciónde Salmonella spp., en muestras coprológicas porcinas es baja, y nula para E. coli O157:H7, sin embargo, se debemantener la vigilancia sobre estos patógenos, por lo que se recomienda continuar los estudios epidemiológicos.
Moore, Aimee M; Ahmadi, Sara; Patel, Sanket; Gibson, Molly K; Wang, Bin; Ndao, Malick I; Deych, Elena; Shannon, William; Tarr, Phillip I; Warner, Barbara B; Dantas, Gautam
The early life of the human host marks a critically important time for establishment of the gut microbial community, yet the developmental trajectory of gut community-encoded resistance genes (resistome) is unknown. We present a longitudinal study of the fecal antibiotic resistome of healthy amoxicillin-exposed and antibiotic-naive twins and their mothers during the first year of life. We extracted metagenomic DNA (mgDNA) from fecal samples collected from three healthy twin pairs at three timepoints (1 or 2 months, 6 or 7 months, and 11 months) and from their mothers (collected at delivery). The mgDNA was used to construct metagenomic expression libraries in an Escherichia coli host. These libraries were screened for antibiotic resistance, and functionally selected resistance genes were sequenced and annotated. A diverse fecal resistome distinct from the maternal resistome was apparent by 2 months of age, and infants' fecal resistomes included resistance to clinically important broad-spectrum beta-lactam antibiotics (e.g., piperacillin-tazobactam, aztreonam, cefepime) not found in their mothers. Dissemination of resistance genes among members of a given family was positively correlated with sharing of those same resistance genes between unrelated families, potentially identifying within-family sharing as a marker of resistance genes emerging in the human community at large. Finally, we found a distinct developmental trajectory for a community-encoded function: chloramphenicol resistance. All study subjects at all timepoints harbored chloramphenicol resistance determinants, but multidrug efflux pumps (rarely found in mothers) were the primary effectors of chloramphenicol resistance in young infants. Chloramphenicol acetyltransferases were more common in mothers than in infants and were found in nearly all the infants at later timepoints. Our results suggest that healthy 1-2-month-old infants' gut microbes harbor clinically relevant resistance genes distinct from
Alyamani, Essam J; Khiyami, Mohamed A; Booq, Rayan Y; Alnafjan, Basel M; Altammami, Musaad A; Bahwerth, Fayez S
Acinetobacter baumannii is a common opportunistic pathogen that causes major nosocomial infections in hospitals. In this study, we hypothesized a high prevalence of A. baumanni ESBL (extended-spectrum beta-lactamase) among all collected isolates. A. baumannii isolates (n = 107) from ICU (Intensive care unit) of local hospitals in Makkah were phenotypically and genotypically characterized. The identity and antibiotic susceptibility of A. baumannii strains were determined using the Vitek-2 system. The identified ESBL producers were further analyzed by PCR and sequencing followed by MLST typing. bla TEM , bla SHV , and the bla CTX-M-group genes 1, 2, 8, 9, and 25 were investigated. Furthermore, bla OXA51-like and bla OXA23-like genes were also examined in the carbapenem-resistant A. baumannii isolates. Our data indicated a high prevalence of A. baumannii ESBL producers among the collected strains. Of the 107 A. baumannii isolates, 94 % were found to be resistant to cefepime and ceftazidime, and aztreonam using the Vitek 2 system. The genes detected encoded TEM, OXA-51-like and OXA-23-like enzymes, and CTX-M-group proteins 1, 2, 8, 9, and 25. MLST typing identified eight sequence type (ST) groups. The most dominant STs were ST195 and ST557 and all of them belong to worldwide clonal complex (CC) 2. This study has shown that there is a high prevalence of antimicrobial resistance in A. baumannii. The diversity of STs may suggest that new ESBL strains are constantly emerging. The molecular diversity of the ESBL genes in A. baumannii may have contributed to the increased antimicrobial resistance among all isolates.
Ehrmann, E; Jolivet-Gougeon, A; Bonnaure-Mallet, M; Fosse, T
In oral microbiome, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of fastidious Capnocytophaga species. The performances of six culture media (blood agar, chocolate blood agar, VCAT medium, CAPE medium, bacitracin chocolate blood agar and VK medium) were compared with literature data concerning five other media (FAA, LB, TSBV, CapR and TBBP media). To understand variable growth on selective media, the MICs of each antimicrobial agent contained in this different media (colistin, kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, vancomycin, aztreonam and bacitracin) were determined for all Capnocytophaga species. Overall, VCAT medium (Columbia, 10% cooked horse blood, polyvitaminic supplement, 3·75 mg l(-1) of colistin, 1·5 mg l(-1) of trimethoprim, 1 mg l(-1) of vancomycin and 0·5 mg l(-1) of amphotericin B, Oxoid, France) was the more efficient selective medium, with regard to the detection of Capnocytophaga species from oral samples (P culture, a simple blood agar allowed the growth of all Capnocytophaga species. Nonetheless, in oral samples, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of Capnocytophaga species. The demonstrated superiority of VCAT medium made its use essential for the optimal detection of this bacterial genus. This work showed that extreme caution should be exercised when reporting the isolation of Capnocytophaga species from oral polymicrobial samples, because the culture medium is a determining factor. © 2013 The Society for Applied Microbiology.
Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D., E-mail: email@example.com
Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation.
Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy
Full Text Available Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF. We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146 detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE revealed that a single genotype (clone FQSE-A produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089 was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination
Brennan-Krohn, Thea; Truelson, Katherine A; Smith, Kenneth P; Kirby, James E
Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights
Roberts, Marilyn C; No, David B; Marzluff, John M; Delap, Jack H; Turner, Robert
Vancomycin-resistant enterococci [VRE] have been isolated from municipal, hospital and agricultural wastewater, recreational beaches, wild animals, birds and food animals around the world. In this study, American crows (Corvus brachyrhynchos) from sewage treatment plants (WWTP), dairy farms, and a large roost in a restored wetland with corresponding environmental samples were cultured for VRE. A total of 245 samples [156 crows, 89 environmental] were collected and screened for acquired vanA, vanB and/or intrinsic vanC1 genes. Samples were enriched overnight in BHI supplemented with 20μg/mL aztreonam, 4μg/mL vancomycin and plated on m-Enterococcus agar media supplemented with 6μg/mL vancomycin. Selected colonies were grown on BHI media supplemented with 18μg/mL vancomycin. Of these, 24.5% of the crow and 55% the environmental/cow samples were VRE positive as defined by Enterococcus spp. able to grow on media supplemented with 18μg/mL vancomycin. A total of 122 VRE isolates, 43 crow and 79 environmental isolates were screened, identified to species level using 16S sequencing and further characterized. Four vanA E. faecium and multiple vanC1 E. gallinarum were identified from crows isolated from three sites. E. faecium vanA and E. gallinarum vanC1 along with other Enterococcus spp. carrying vanA, vanB, vanC1 were isolated from three environments. All enterococci were multidrug resistant. Crows were more likely to carry vanA E. faecium than either the cow feces or wetland waters/soils. Comparing E. gallinarum vanC1 from crows and their environment would be useful in determining whether crows share VRE strains with their environment. Copyright © 2016 Elsevier B.V. All rights reserved.
Hashem, Hany; Hanora, Amro; Abdalla, Salah; Shawky, Alaa; Saad, Alaa
Resistant Pseudomonas aeruginosa is a serious concern for antimicrobial therapy, as the common isolates exhibit variable grades of resistance, involving beta-lactamase enzymes, beside native defense mechanisms. The present study was designed to determine the occurrence of Metallo-β- Lactamases (MBL) and Amp C harboring P. aeruginosa isolates from Suez Canal university hospital in Ismailia, Egypt. A total of 147 P. aeruginosa isolates, recovered from 311 patients during a 10-month period, were collected between May 2013 and February 2014; the isolates were collected from urine, wound and sputum. Minimum inhibitory concentration (MIC) determined by agar dilution methods was ≥2 μg/mL for meropenem and imipenem. Identification of P. aeruginosa was confirmed using API 20NE. Metallo-β- Lactamases and Amp C were detected based on different phenotypic methods. Overall, 26.5% of P. aeruginosa isolates (39/147) were carbapenem resistant isolates. Furthermore, 64.1% (25/39) were MBL producers, these isolates were screened by the combined disc and disc diffusion methods to determine the ability of MBL production. Both MBL and Amp C harbored P. aeruginosa isolates were 28% (7/25). Sixty-four percent of P. aeruginosa isolates were multidrug resistant (MDR) (16/25). The sensitivity toward polymyxin, imipenem, norfloxacin, piperacillin-tazobactam and gentamicin was 99%, 91%, 88%, 82% and 78%, respectively. The resistance rate towards cefotaxime, ceftazidime, cefepime, aztreonam and meropenem was 98.6%, 86%, 71.4%, 34% and 30%, respectively. Multidrug resistance was significantly associated with MBL production in P. aeruginosa . Early detection of MBL-producing P. aeruginosa and hospital antibiotic policy prescription helps proper antimicrobial therapy and avoidance of dissemination of these multidrug resistance isolates.
Full Text Available Shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. However, only limited data is available on the global phenotypic and genotypic characteristics of S. flexneri 1b. In the present study, 40 S. flexneri 1b isolates from different regions of China were confirmed by serotyping and biochemical characterization. Antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susceptibility profiles varied between geographical locations. Strains from Yunnan were far more resistant than those from Xinjiang, while only one strain from Shanghai was resistant to ceftazidime and aztreonam. Fifteen cephalosporin resistant isolates were identified in this study. ESBL genes (blaSHV, blaTEM, blaOXA, and blaCTX-M and ampC genes (blaMOX, blaFOX, blaMIR(ACT-1, blaDHA, blaCIT and blaACC were subsequently detected among the 15 isolates. The results showed that these strains were positive only for blaTEM, blaOXA, blaCTX-M, intI1, and intI2. Furthermore, pulsed-field gel electrophoresis (PFGE analysis showed that the 40 isolates formed different profiles, and the PFGE patterns of Xinjiang isolates were distinct from Yunnan and Shanghai isolates by one obvious, large, missing band. In summary, similarities in resistance patterns were observed in strains with the same PFGE pattern. Overall, the results supported the need for more prudent selection and use of antibiotics in China. We suggest that antibiotic susceptibility testing should be performed at the start of an outbreak, and antibiotic use should be restricted to severe Shigella cases, based on resistance pattern variations observed in different regions. The data obtained in the current study might help to develop a strategy for the treatment of infections caused by S. flexneri 1b in China.
Full Text Available The presence of multiresistance to the effects of antibiotics and chemotherapeutics and extended spectrum beta-lactamase were examined in 45 strains of E. coli and 35 strains of Salmonella. The strains of E. coli originated from several species of domestic animals: dogs, cats, poultry, and cattle, and 30 strains of Salmonella originated from poultry, 4 strains from cattle, and 1 strain from swine. The presence of the following serovarieties was established using serological examinations: Salmonella Enteritidis 17 strains, Salmonella Gallinarum 1 strain, Salmonella Hartford 5 strains, Salmonella Anatum 1 strain, Salmonella Typhimurium 4 strains, Salmonella Agona 1 strain, Salmonella Infantis 1 strain, Salmonella Thompson var. Berlin 1 strain, Salmonella Tennessee 1 strain, Salmonella Senftenberg 1 strain, Salmonella Glostrup 1 strain, and Salmonella Hadar 1 strain. In the examinations of the listed strains we used antibiogram discs of ampicillin, amoxicillin with clavulanic acid, cephalexin, cephtriaxon, cephotaxim, cephtazidime, aztreonam, gentamycin, chloramphenicol, tetracycline, cyprofloxacine, and a combination of sulphamethoxasole and trimethoprim. The lowest prevalence of multiresistance in E. Coli strains to 3 or more antibiotics was established in dogs 20%, and the highest in 60% strains originating from swine. In 62.88% strains of Salmonella we established sensitivity to all applied antibiotics. Resistance was also established in a small number of the examined strains to ampicillin (11 strains, to tetracycline (5 strains, to amoxicillin with clavulanic acid (5 strains, to sulphamethoxasole with trimethoprim (5 strains, to gentamycin (3 strains, and to cloramphenicol (1 strain. Of all the examined strains of Salmonella, 6 strains originating from poultry exhibited multiresistence. The presence of extended spectrum beta-lactamase effects examined using the ESBL test, was not established in strains of E. coli and Salmonella strains.
Flores Ribeiro, Angela; Bodilis, Josselin; Alonso, Lise; Buquet, Sylvaine; Feuilloley, Marc; Dupont, Jean-Paul; Pawlak, Barbara
Aquatic environments could play a role in the spread of antibiotic resistance genes by enabling antibiotic-resistant bacteria transferred through wastewater inputs to connect with autochthonous bacteria. Consequently, drinking water could be a potential pathway to humans and animals for antibiotic resistance genes. The aim of this study was to investigate occurrences of Escherichia coli and Pseudomonas spp. in drinking water produced from a karst, a vulnerable aquifer with frequent increases in water turbidity after rainfall events and run-offs. Water samples were collected throughout the system from the karstic springs to the drinking water tap during three non-turbid periods and two turbid events. E. coli densities in the springs were 10- to 1000-fold higher during the turbid events than during the non-turbid periods, indicating that, with increased turbidity, surface water had entered the karstic system and contaminated the spring water. However, no E. coli were isolated in the drinking water. In contrast, Pseudomonas spp. were isolated from the drinking water only during turbid events, while the densities in the springs were from 10- to 100-fold higher than in the non-turbid periods. All the 580 Pseudomonas spp. isolates obtained from the sampling periods were resistant (to between 1 and 10 antibiotics), with similar resistance patterns. Among all the Pseudomonas isolated throughout the drinking water production system, between 32% and 86% carried the major resistance pattern: ticarcillin, ticarcillin-clavulanic acid, cefsulodin, and/or aztreonam, and/or sulfamethoxazol-trimethoprim, and/or fosfomycin. Finally, 8 Pseudomonas spp. isolates, related to the Pseudomonas putida and Pseudomonas fluorescens species, were isolated from the drinking water. Thus, Pseudomonas could be involved in the dissemination of antibiotic resistance via drinking water during critical periods. Copyright © 2014 Elsevier B.V. All rights reserved.
Sy, S K B; Derendorf, H
A β-lactamase inhibitor (BLI) confers susceptibility of β-lactamase-expressing multidrug resistant (MDR) organisms to the partnering β-lactam (BL). To discuss the experimental design and modelling strategies for two-drug combinations, using ceftazidime- and aztreonam-avibactam combinations, as examples. The information came from several publications on avibactam in vitro time-kill studies and corresponding pharmacodynamic models. The experimental design to optimally gather crucial information from constant-concentration time-kill studies is to use an agile matrix of two-drug concentration combinations that cover 0.25- to 4-fold BL minimum inhibitory concentration (MIC) relative to the BLI concentrations to be tested against the particular isolate. This shifting agile design can save substantial costs and resources, without sacrificing crucial information needed for model development. The complex synergistic BL/BLI interaction is quantitatively explored using a semi-mechanistic pharmacokinetic-pharmacodynamic (PK/PD) mathematical model that accounts for antimicrobial activities in the combination, bacteria-mediated BL degradation and inhibition of BL degradation by BLI. A predictive mathematical formulation for the two-drug killing effects preserves the correlation between the model-derived EC 50 of BL and the BL MIC. The predictive value of PK/PD model is evaluated against external data that were not used for model development, including but not limited to in vitro hollow fibre and in vivo murine infection models. As a framework for translational predictions, the goal of this modelling strategy is to significantly decrease the decision-making time by running clinical trial simulations with MIC-substituted EC 50 function for isolates of comparable susceptibility through established correlation between BL MIC and EC 50 values. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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.
Harada, Kazuki; Niina, Ayaka; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Miyamoto, Tadashi; Kataoka, Yasushi
Large-scale monitoring of resistance to 14 antimicrobial agents was performed using 103 Proteus mirabilis strains isolated from dogs in Japan. Resistant strains were analysed to identify their resistance mechanisms. Rates of resistance to chloramphenicol, streptomycin, enrofloxacin, trimethoprim/sulfamethoxazole, kanamycin, ampicillin, ciprofloxacin, cephalothin, gentamicin, cefoxitin and cefotaxime were 20.4, 15.5, 12.6, 10.7, 9.7, 8.7, 5.8, 2.9, 2.9, 1.9 and 1.9%, respectively. No resistance to ceftazidime, aztreonam or imipenem was found. Class 1 and 2 integrases were detected in 2.9 and 11.7% of isolates, respectively. Class 1 integrons contained aadB or aadB-catB-like-blaOXA10-aadA1, whereas those of class 2 contained sat-aadA1, dhfr1-sat-aadA1 or none of the anticipated resistance genes. Of five distinct plasmid-mediated quinolone-resistance (PMQR) genes, only qnrD gene was detected in 1.9% of isolates. Quinolone-resistance determining regions (QRDRs) of gyrA and parC from 13 enrofloxacin-intermediate and -resistant isolates were sequenced. Seven strains had double mutations and three had single mutations. Three of nine ampicillin-resistant isolates harboured AmpC-type β-lactamases (i.e. blaCMY-2, blaCMY-4 and blaDHA-1). These results suggest that canine Proteus mirabilis deserves continued surveillance as an important reservoir of antimicrobial resistance determinants. This is the first report, to our knowledge, describing integrons, PMQRs and QRDR mutations in Proteus mirabilis isolates from companion animals. © 2014 The Authors.
Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D
The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying
Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive
Full Text Available Objetivo: Estudiar la presencia de beta-lactamasas de espectro extendido (BLEE e identificar los tipos Temoniera (TEM y sulfidrilo variable (SHV producidas por cepas de Escherichia coli y Klebsiella pneumoniae en dos hospitales de Lima. Material y Métodos: La selección y confirmación de cepas productoras de BLEE se realizó mediante pruebas de susceptibilidad antimicrobiana, utilizando los criterios de la National Committee for Clinical Laboratory Standards (NCCLS; la identificación de los genes blaTEM y blaSHV se realizó mediante el análisis de la reacción en cadena de la polimerasa (PCR para su posterior secuenciamiento genético. Resultados: Se recolectó consecutivamente entre julio y septiembre de 2000, 137 cepas de Escherichia coli y 18 cepas de Klebsiella pneumoniae. La mayoría mostró alta resistencia a las cefalosporinas de tercera generación y aztreonam; 2,9% del total de E.coli y 44,4% del total de K.pneumoniae aisladas fueron confirmadas como productoras de BLEE. Todas las cepas productoras de BLEE fueron multirresistentes y la mayoría presentó co-resistencia a sulfametoxazol/trimetoprim, amikacina, gentamicina y ciprofoxacina. Se identificó la presencia del gen blaTEM en 4 cepas (3 K. pneumoniae y 1 E. coli y el gen blaSHV en 6 cepas (3 K. pneumoniae y 3 E. coli. El secuenciamiento de los correspondientes genes confirmó las BLEEs TEM-10 y SHV-5. Conclusión: Se demostró la presencia de BLEE tipo TEM y SHV, asociado a multirresistencia antibiótica.
Chin, Bum Sik; Kim, Myung Soo; Han, Sang Hoon; Shin, So Youn; Choi, Hee Kyung; Chae, Yun Tae; Jin, Sung Joon; Baek, Ji-Hyeon; Choi, Jun Yong; Song, Young Goo; Kim, Chang Oh; Kim, June Myung
Urinary tract infection (UTI) is the most frequent cause of bacteremia/sepsis in elderly people and increasing antimicrobial resistance in uropathogens has been observed. To describe the characteristics of bacteremic UTI in elderly patients and to identify the independent risk factors of all-cause in-hospital mortality, a retrospective cohort study of bacteremic UTI patients of age over 65 was performed at a single 2000-bed tertiary hospital. Bacteremic UTI was defined as the isolation of the same organism from both urine and blood within 48 h. Eighty-six elderly bacteremic UTI patients were enrolled. Community-acquired infection was the case for most patients (79.1%), and Escherichia coli accounted for 88.6% (70/79) among Gram-negative organisms. Non-E. coli Gram-negative organisms were more frequent in hospital-acquired cases and male patients while chronic urinary catheter insertion was related with Gram-positive urosepsis. The antibiotic susceptibility among Gram-negative organisms was not different depending on the source of bacteremic UTI, while non-E. coli Gram-negative organisms were less frequently susceptible for cefotaxime, cefoperazone/sulbactam, and aztreonam. All-cause in-hospital mortality was 11.6%, and functional dependency (adjusted hazard ratio=HR=10.9, 95% confidence interval=95%CI=2.2-54.6) and low serum albumin (adjusted HR=27.0, 95%CI=2.0-361.2) were independently related with increased all-cause in-hospital mortality. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.
Habibi, Asghar; Honarmand, Ramin
Putative virulence factors are responsible for the pathogenicity of UTIs caused by Pseudomonas aeruginosa (P. aeruginosa). Resistance of P. aeruginosa to commonly used antibiotics is caused by the extreme overprescription of those antibiotics. The goal of the present study was to investigate the prevalence of virulence factors and the antibiotic resistance patterns of P. aeruginosa isolates in UTI cases in Iran. Two hundred and fifty urine samples were collected from patients who suffered from UTIs. Samples were cultured immediately, and those that were P. aeruginosa-positive were analyzed for the presence of virulence genes using polymerase chain reaction (PCR) testing. Antimicrobial susceptibility testing (AST) was performed using the disk diffusion method. Of the 250 urine samples analyzed, 8 samples (3.2%) were positive for P. aeruginosa. The prevalence of P. aeruginosa in male and female patients was 2.7% and 3.5%, respectively, (P = 0.035). In patients less than 10 years old, it was 4.2%, and in patients more than 55 years old, it was 4.2%. These were the most commonly infected groups. The highest levels of resistance were seen against ampicillin (87.5%), norfloxacin (62.5%), gentamycin (62.5%), amikacin (62.5%), and aztreonam (62.5%), while the lowest were seen for meropenem (0%), imipenem (12.5%), and polymyxin B (12.5%). LasB (87.5%), pclH (75%), pilB (75%), and exoS (75%) were the most commonly detected virulence factors in the P. aeruginosa isolates. It is logical to first prescribe meropenem, imipenem, and polymyxin B in cases of UTIs caused by P. aeruginosa. Medical practitioners should be aware of the presence of levels of antibiotic resistance in hospitalized UTI patients in Iran.
O. A. Nazarchuk
Full Text Available Background. Infections caused by Pseudomonas are one of the topical issues of medicine. Objective. The aim of the research was to study sensityvity to antibiotics, antiseptics of P. aeruginosa clinical strains that cause infectious complications in patients with burns. Methods. Microbiological study of biological material, received from 435 patients with burns of the 3rd-4th stages (2011-2015 years. In early terms of burn disease 127 clinical strains of P. aeruginosa were isolated from patients. Standard methods were used to identify clinical isolates of P. aeruginosa by their morphological, tinctirial, culture and biochemical properties. The research of antimicrobial action of antiseptics, antibiotics against Pseudomonas were carried out by means of standard methods according to the Directive of the Ministry of Health of Ukraine (No. 167 from 05.04.2007 р. and guidelines of National Committee of Clinical and Laboratory Study (NCCLS, 2002. Results. It was established that P. aeruginosa caused infectious complications in 23.9% of patients among other pathogens. Clinical isolates of P. aeruginosa were found to be low sensitive to amoxicillin/clavulanate (30.76%, ceftazidime (25.92%, cefoperazonum/sulbactam (46.15%, aztreonam (51.85%, tobramycin (38.46%, amicacin (70.34%, doxiciclini (26.92%, fluoroquinolones (59.26%. The analitical progistic criteria of decrease of sensitivity to ceftazidime, cefepim, meropenem and gatifloxacin were found in P. aeruginosa. This pathogen was determined to be sensitive to decasan ®, antimicrobial composition of decamethoxine ®, iodine pvidone. Conclusions. Clinical strains of Pseudomonas aeruginosa, being highly resistant to antibiotics, are also very sensitive to antiseptics decasan ®, antimicrobial of decamethoxine®, povidone iodine.
Nukaga, Michiyoshi; Papp-Wallace, Krisztina M; Hoshino, Tyuji; Lefurgy, Scott T; Bethel, Christopher R; Barnes, Melissa D; Zeiser, Elise T; Johnson, J Kristie; Bonomo, Robert A
Ceftazidime-avibactam is a "second-generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases, and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases, is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in the Citrobacter AmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active-site topologies affect avibactam inhibition, we tested a panel of clinical Enterobacteriaceae isolates producing bla FOX using ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producing bla FOX ; two isolates, one expressing bla FOX-4 and the other producing bla FOX-5 , displayed an MIC of 16 μg/ml for the combination. FOX-4 possessed a k 2 / K value of 1,800 ± 100 M -1 · s -1 and an off rate ( k off ) of 0.0013 ± 0.0003 s -1 Mass spectrometry showed that the FOX-4-avibactam complex did not undergo chemical modification for 24 h. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5-Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the Pseudomonas -derived cephalosporinase 1 (PDC-1)-avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen
Deepti P. Karumathil
Full Text Available Multi-drug resistant (MDR Acinetobacter baumannii is a major nosocomial pathogen causing a wide range of clinical conditions with significant mortality rates. A. baumannii strains are equipped with a multitude of antibiotic resistance mechanisms, rendering them resistant to most of the currently available antibiotics. Thus, there is a critical need to explore novel strategies for controlling antibiotic resistance in A. baumannii. This study investigated the efficacy of two food-grade, plant-derived antimicrobials (PDAs, namely trans-cinnamaldehyde (TC and eugenol (EG in decreasing A. baumannii’s resistance to seven β-lactam antibiotics, including ampicillin, methicillin, meropenem, penicillin, aztreonam, amoxicillin, and piperacillin. Two MDR A. baumannii isolates (ATCC 17978 and AB 251847 were separately cultured in tryptic soy broth (∼6 log CFU/ml containing the minimum inhibitory concentration (MIC of TC or EG with or without the MIC of each antibiotic at 37°C for 18 h. A. baumannii strains not exposed to the PDAs or antibiotics served as controls. Following incubation, A. baumannii counts were determined by broth dilution assay. In addition, the effect of PDAs on the permeability of outer membrane and efflux pumps in A. baumannii was measured. Further, the effect of TC and EG on the expression of A. baumannii genes encoding resistance to β-lactam antibiotics (blaP, efflux pumps (adeABC, and multi-drug resistant protein (mdrp was studied using real-time quantitative PCR (RT-qPCR. The experiment was replicated three times with duplicate samples of each treatment and control. The results from broth dilution assay indicated that both TC and EG in combination with antibiotics increased the sensitivity of A. baumannii to all the tested antibiotics (P < 0.05. The two PDAs inhibited the function of A. baumannii efflux pump, (AdeABC, but did not increase the permeability of its outer membrane. Moreover, RT-qPCR data revealed that TC and EG
Karumathil, Deepti P; Nair, Meera Surendran; Gaffney, James; Kollanoor-Johny, Anup; Venkitanarayanan, Kumar
Multi-drug resistant (MDR) Acinetobacter baumannii is a major nosocomial pathogen causing a wide range of clinical conditions with significant mortality rates. A. baumannii strains are equipped with a multitude of antibiotic resistance mechanisms, rendering them resistant to most of the currently available antibiotics. Thus, there is a critical need to explore novel strategies for controlling antibiotic resistance in A. baumannii . This study investigated the efficacy of two food-grade, plant-derived antimicrobials (PDAs), namely trans -cinnamaldehyde (TC) and eugenol (EG) in decreasing A. baumannii 's resistance to seven β-lactam antibiotics, including ampicillin, methicillin, meropenem, penicillin, aztreonam, amoxicillin, and piperacillin. Two MDR A. baumannii isolates (ATCC 17978 and AB 251847) were separately cultured in tryptic soy broth (∼6 log CFU/ml) containing the minimum inhibitory concentration (MIC) of TC or EG with or without the MIC of each antibiotic at 37°C for 18 h. A. baumannii strains not exposed to the PDAs or antibiotics served as controls. Following incubation, A. baumannii counts were determined by broth dilution assay. In addition, the effect of PDAs on the permeability of outer membrane and efflux pumps in A. baumannii was measured. Further, the effect of TC and EG on the expression of A. baumannii genes encoding resistance to β-lactam antibiotics ( blaP ), efflux pumps ( adeABC ), and multi-drug resistant protein ( mdrp ) was studied using real-time quantitative PCR (RT-qPCR). The experiment was replicated three times with duplicate samples of each treatment and control. The results from broth dilution assay indicated that both TC and EG in combination with antibiotics increased the sensitivity of A. baumannii to all the tested antibiotics ( P increase the permeability of its outer membrane. Moreover, RT-qPCR data revealed that TC and EG down-regulated the expression of majority of the genes associated with β-lactam antibiotic
Zhang, Xingyu; Chen, Di; Xu, Guifeng; Huang, Weichun; Wang, Xing
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent
Proposal to rename Carnobacterium inhibens as Carnobacterium inhibens subsp. inhibens subsp. nov. and description of Carnobacterium inhibens subsp. gilichinskyi subsp. nov., a psychrotolerant bacterium isolated from Siberian permafrost.
Nicholson, Wayne L; Zhalnina, Kateryna; de Oliveira, Rafael R; Triplett, Eric W
A novel, psychrotolerant facultative anaerobe, strain WN1359(T), was isolated from a permafrost borehole sample collected at the right bank of the Kolyma River in Siberia, Russia. Gram-positive-staining, non-motile, rod-shaped cells were observed with sizes of 1-2 µm long and 0.4-0.5 µm wide. Growth occurred in the range of pH 5.8-9.0 with optimal growth at pH 7.8-8.6 (pH optimum 8.2). The novel isolate grew at temperatures from 0-37 °C and optimal growth occurred at 25 °C. The novel isolate does not require NaCl; growth was observed between 0 and 8.8 % (1.5 M) NaCl with optimal growth at 0.5 % (w/v) NaCl. The isolate was a catalase-negative, facultatively anaerobic chemo-organoheterotroph that used sugars but not several single amino acids or dipeptides as substrates. The major metabolic end-product was lactic acid in the ratio of 86 % l-lactate : 14 % d-lactate. Strain WN1359(T) was sensitive to ampicillin, chloramphenicol, fusidic acid, lincomycin, monocycline, rifampicin, rifamycin SV, spectinomycin, streptomycin, troleandomycin and vancomycin, and resistant to nalidixic acid and aztreonam. The fatty acid content was predominantly unsaturated (70.2 %), branched-chain unsaturated (11.7 %) and saturated (12.5 %). The DNA G+C content was 35.3 mol% by whole genome sequence analysis. 16S rRNA gene sequence analysis showed 98.7 % sequence identity between strain WN1359(T) and Carnobacterium inhibens. Genome relatedness was computed using both Genome-to-Genome Distance Analysis (GGDA) and Average Nucleotide Identity (ANI), which both strongly supported strain WN1359(T) belonging to the species C. inhibens. On the basis of these results, the permafrost isolate WN1359(T) represents a novel subspecies of C. inhibens, for which the name Carnobacterium inhibens subsp. gilichinskyi subsp. nov. is proposed. The type strain is WN1359(T) ( = ATCC BAA-2557(T) = DSM 27470(T)). The subspecies Carnobacterium inhibens subsp. inhibens subsp. nov. is created automatically. An
Tawfik, Abdulkader F; Shibl, Atef M; Aljohi, Mohamed A; Altammami, Musaad A; Al-Agamy, Mohamed H
We determined the prevalence rate of classes A, B and D β-lactamases among extended-spectrum cephalosporin (ESC)-non-susceptible Pseudomonas aeruginosa clinical isolates from burned patients. Disc susceptibility testing was performed on 156 P. aeruginosa isolates collected during 2010 at Prince Salman Hospital in Riyadh, Saudi Arabia. Phenotypic screening of ESBLs and MBLs in the isolates resistant to ceftazidime (MIC>8 mg/L) was carried out. Genes encoding ESBLs and MBL were sought by PCR in ESBL- and MBL-producing isolates. The resistance rate to ceftazidime was 22.43%. The resistance rates for ESC-non-susceptible P. aeruginosa isolates to piperacillin, piperacillin/tazobactam, cefepime, aztreonam, imipenem, amikacin, gentamicin and ciprofloxacin were 100%, 71.14%, 88.57%, 48.57%, 70.0%, 82.5%, 87.5%, and 90.0% respectively. No resistance was detected to polymyxine B. The prevalence of ESBL and MBL in ESC-non-susceptible P. aeruginosa was 69.44% and 42.85%, respectively. The prevalence of structural genes for VEB-1, OXA-10 and GES ESBLs in P. aeruginosa was 68%, 56% and 20%, respectively. VIM gene was detected in 15 (100%) of MBL-producing isolates. OXA-10 like gene was concomitant with VEB, GES and/or VIM. Eight isolates harbored OXA-10 with VEB (imipenem MIC 6-8 mg/L), while five isolates harbored OXA-10 with VIM (imipenem MIC ≥ 32 mg/L) and one isolate contained OXA-10, VEB and GES (imipenem MIC 8 mg/L). PER was not detected in this study. VEB-1 and OXA-10 are the predominant ESBL genes and bla(VIM) is the dominate MBL gene in ESC-non-sensitive P. aeruginosa isolates in Saudi Arabia. VEB, OXA-10 and GES ESBLs have not been reported previously in Saudi Arabia and GES has not been reported previously in Middle East and North Africa. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.
Mediavilla, José R; Patrawalla, Amee; Chen, Liang; Chavda, Kalyan D; Mathema, Barun; Vinnard, Christopher; Dever, Lisa L; Kreiswirth, Barry N
Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of
Oli, Angus N; Akabueze, Vivian B; Ezeudu, Chijioke E; Eleje, George U; Ejiofor, Obiora S; Ezebialu, Ifeanyichukwu U; Oguejiofor, Charlotte B; Ekejindu, Ifeoma M; Emechebe, George O; Okeke, Kenneth N
Urinary Tract Infection (UTI) is a common contagion among men and women with the incidence relatively higher among women due to their differing anatomy. An understanding of the kind of pathogens implicated in urinary tract infections as well as antibiotic susceptibility profiling may help the clinician make rationally correct empirical choice in their treatment. This study is aimed at determining the type and antibiotic susceptibility pattern of bacterial uropathogens isolated from female patients attending Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH), Awka, Nigeria. Two hundred and forty patients with clinically diagnosed UTI and who were on at least 5 days' antibiotic holiday were recruited into the study. Their demographic characteristics were captured using pre-tested questionnaire. Their clean catch mid-stream urine samples were collected using sterile universal container and sent to the Microbiology Department for processing. Within 30 minutes of samples collection, the specimens were cultured and the isolates were identified, after 24 h of incubation, using standard microbiological techniques. Antibiotic susceptibility tests were done with standard antibiotic discs using the Kirby-bauer disc diffusion method. Out of the 240 urine samples, 89.17% yielded significant bacteriuria. The pathogens implicated were Escherichia coli (28.5%), Staphylococcus aureus (28.0%), Salmonella spp (22.8%) and Pseudomonas aeruginosa (20.5%). HIV status, patients age, pregnancy status and marital status all significantly affected bacteriuria rate (p value 0.05). The pattern of microbial resistance to antibiotics suggests that ceftazidime, fosfomycin and cefoxitin may not be used as first-line agents in the empirical treatment of UTIs rather; levofloxacin, meropenem or aztreonam should be considered. Levofloxacin was significantly effective against all the isolates and may be administered empirically while waiting for the culture result (Mean % susceptibility
Full Text Available L’Uro-Quick, un sistema automatizzato ampiamente utilizzato per lo screening delle batteriurie sui campioni d’urina, è stato precedentemente impiegato per la valutazione della sensibilità agli antibiotici negli uropatogeni e per l’identificazione di resistenze ben caratterizzate veicolate da diverse specie batteriche. In questo studio sono stati esaminati utilizzando la metodica classica Kirby-Bauer per la determinazione dell’antibiotico sensibilità patogeni isolati durante il periodo settembre 2003 - marzo 2004 in reparti di terapia intensiva di un grande ospedale italiano e i risultati sono stati confrontati con quelli ottenuti con il nuovo sistema rapido Uro-Quick. L’antibiotico (in concentrazione appropriata è stato introdotto in una cuvetta Uro-Quick contenente 2 ml di Mueller-Hinton brodo, successivamente sono stati addizionati 0.5 ml di sospensione del ceppo da saggiare (5x105 CFU/ml. Una cuvetta priva di farmaco è stata utilizzata come controllo. Dopo 3 o 5 ore di incubazione (per i ceppi Gram-negativi o Gram-positivi rispettivamente i risultati sono stati interpretati nel seguente modo: l’assenza di sviluppo indicava sensibilità, mentre una curva di crescita analoga a quella del controllo rappresentava un ceppo resistente. I microrganismi Gram-negativi sono stati saggiati con ciprofloxacina (CIP, ampicillina (AM, piperacillina (PIP, aztreonam (ATM, amoxicillina-clavulanato (AMC, piperacillina/tazobactam (TZP, imipenem (IPM, ceftazidime (CAZ, cefotaxime (CTX, cefepime (CFP, cefuroxime (CXM, ceftriaxone (CRO, amikacina (AN, gentamicina (GM e trimethoprim-sulfametossazolo (SXT. I Gram-positivi, invece, sono stati saggiati con ciprofloxacina (CIP, clindamicina (CM, eritromicina (E, rifampicina (RA, ampicillina (AM, penicillina (P, oxacillina (OXA, imipenem (IPM, gentamicina (GM, streptomicina (S, tetraciclina (TE, trimethoprim – sulfametazolo (SXT, vancomicina (VA e linezolid (LZD. Sono stati esaminati 197 ceppi Gram
A. G. Afinogenova
Full Text Available The Enterobacteriaceae antibiotics resistance depends on a combination of several mechanisms, such as the beta-lactamases overproduction, the microbial cell reduction outer membrane permeability (usually associated with loss of protein porin, the presence of efflux systems. Particularly noteworthy are the metallo-beta-lactamases (MBL whose presence causes resistance of gram-negative microorganisms to all beta-lactam antibiotics (in some cases except aztreonam. Currently there are no MBL inhibitors permitted for use in the clinic. The effective inhibitors search for carbapenem-resistant bacteria’ MBL authorized for use in the clinic and reinforcing effects of carbapenems, served as the basis for the present study. The work was carried out in three stages: 1 creating a model system using a standard enzyme reagent metallo-beta-lactamase P. aeruginosa recombinant expressed in E. coli, to evaluate the increasing of minimal inhibitory concentrations (MIC of carbapenems against previously sensitive Gram-negative microorganisms strains in vitro; 2 evaluation of MBL promising inhibitors in the presence of the same standard enzyme reagent; 3 evaluation of the ability of the identified inhibitors increase the carbapenems effects against clinical isolates of Gram-negative microorganisms producing MBL, in terms of the their MIC and fractional inhibitory concentration index (FIC index. The checkerboard array was modified to evaluate the combined use of carbapenems and potential MBL inhibitor — a drug from the group of bisphosphonates — etidronic acid. Using a standard enzyme reagent metallo-beta-lactamase P. aeruginosa recombinant expressed in E. coli, we created a model system that allows to assess the prospects of new inhibitors MBL gram-negative microorganisms. A dose-dependent effect of increasing the meropenem level MIC from reagent MBL quantity in a model system against previously antibiotic sensitive reference strains of microorganisms was
Full Text Available Fluorescein-di-β-D-galactopyranoside (FDG, a fluorogenic compound, is hydrolyzed by β-galactosidase in the cytoplasm of Escherichia coli to produce a fluorescent dye, fluorescein. We found that both FDG and fluorescein were substrates of efflux pumps, and have developed a new method to evaluate efflux-inhibitory activities in E. coli using FDG and a microfluidic channel device. We used E. coli MG1655 wild-type, ΔacrB (ΔB, ΔtolC (ΔC and ΔacrBΔtolC (ΔBC harboring plasmids carrying the mexAB-oprM (pABM or mexXY-oprM (pXYM genes of Pseudomonas aeruginosa. Two inhibitors, MexB-specific pyridopyrimidine (D13-9001 and non-specific Phe-Arg-β-naphthylamide (PAβN were evaluated. The effects of inhibitors on pumps were observed using the microfluidic channel device under a fluorescence microscope. AcrAB-TolC and analogous pumps effectively prevented FDG influx in wild-type cells, resulting in no fluorescence. In contrast, ΔB or ΔC easily imported and hydrolyzed FDG to fluorescein, which was exported by residual pumps in ΔB. Consequently, fluorescent medium in ΔB and fluorescent cells of ΔC and ΔBC were observed in the microfluidic channels. D13-9001 substantially increased fluorescent cell number in ΔBC/pABM but not in ΔBC/pXYM. PAβN increased medium fluorescence in all strains, especially in the pump deletion mutants, and caused fluorescein accumulation to disappear in ΔC. The checkerboard method revealed that D13-9001 acts synergistically with aztreonam, ciprofloxacin, and erythromycin only against the MexAB-OprM producer (ΔBC/pABM, and PAβN acts synergistically, especially with erythromycin, in all strains including the pump deletion mutants. The results obtained from PAβN were similar to the results from membrane permeabilizer, polymyxin B or polymyxin B nonapeptide by concentration. The new method clarified that D13-9001 specifically inhibited MexAB-OprM in contrast to PAβN, which appeared to be a substrate of the pumps and
Full Text Available Réka Bodnár,1,2 Ágnes Mészáros,2 Máté Oláh,2 Tamás Ágh3 1Department of Pediatric Pulmonology, Heim Pál Children’s Hospital, Budapest, Hungary; 2University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary; 3Syreon Research Institute, Budapest, Hungary Background: Inhaled antibiotics (ABs are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF. The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods: A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results: The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3, proportion of adherent patients (>75%–80% of required doses taken ranged from 86% to 97%; in prospective cohort studies (n=3, adherence rates ranged between 36% and 92%, and in retrospective studies (n=4 it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste, and patient satisfaction. Conclusion: The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies and the lack
Poeta, P; Radhouani, H; Gonçalves, A; Figueiredo, N; Carvalho, C; Rodrigues, J; Igrejas, G
A total of 52 Escherichia coli strains isolated from diarrhoeic rabbits were investigated for their enteropathogenic E. coli (EPEC) pathotype by PCR amplification of eae and bfp virulence genes. A total of 22 EPEC isolates were identified, serotyped and studied for antibiotic resistance and screened for the detection of extended-spectrum beta-lactamases (ESBLs). The EPEC isolates belonged to three serogroups (O26, O92 and O103). The most common serogroup (O103:K-:H2) was observed among 17 EPEC strains, the O92:K-serogroup in three isolates (the antibiotic sensitive ones) and the remaining O26:K-serogroup in two isolates (the ESBLs isolates). Resistances to ampicillin and tetracycline were the most frequent and detected followed by resistance to nalidixic acid, streptomycin, trimethoprim-sulphamethoxazole, cefoxitin, gentamicin and ciprofloxacin. All the isolates were sensitive for amikacin, ceftazidime, aztreonam, imipenem, chloramphenicol, tobramycin and amoxicillin + clavulanic acid. Two isolates recovered from two adult animals showed an intermediate susceptibility to cefotaxime, and a positive screening test for ESBL was demonstrated in both. The bla(TEM) gene was demonstrated in the majority of ampicillin-resistant isolates. The aac(3)-II or aac(3)-IV genes were detected in the four gentamicin-resistant isolates. In addition, the aadA gene was detected in 60% of streptomycin-resistant isolates. The tet(A) or tet(B) genes were identified in all tetracycline-resistant isolates. A total of nine EPEC isolates showed the phenotype SXT-resistant, and the sul1 and/or sul2 and/or sul3 genes were detected in all of them. Our findings showed that the molecular detection by the eae and bfp genes by PCR followed by serotyping is useful for monitoring trends in EPEC infections of rabbits allowing the identification of their possible reservoirs. The detection of genes involved in the resistance to antibiotics of different families in a relatively high proportion of faecal E
David Cataño Toro
Full Text Available Introducción: Pseudomonas aeruginosa es una bacteria oportunista Gram negativa particularmente eficiente en la adquisición de mecanismos de resistencia y de alta prevalencia en infecciones nosocomiales en pacientes oncológicos. Objetivo: identificar los factores de riesgo para mortalidad en pacientes oncológicos con aislamiento de P. aeruginosa. Metodología: estudio descriptivo, la población de estudio fueron los casos reportados con aislamiento de P. aeruginosa en el servicio de hospitalización de Oncólogos de Occidente en Pereira, Armenia y Manizales durante el año 2015. Se realizaron análisis univariados y multivariados; la supervivencia se estableció según el método de KaplanMeier. Se estableció un valor de p <0.05. Se usó el software STATA. Se tuvo aval de bioética de la Universidad Tecnológica de Pereira. Resultados: se estudió 41 casos confirmados de cultivos positivos de P. aeruginosa. El sexo masculino (46.3%, anemia (46.3%, neutropenia febril (41%, trombocitopenia (29.3% y haber sido hospitalizado en la unidad de cuidados intensivos (29.3% fueron asociados estadísticamente con mayor mortalidad (p=0.019; con estos resultados se diseñó una escala de riesgo (alfa de Cronbach =0.72. Los pacientes con cuatro de estas exposiciones mostraron mayor riesgo de mortalidad al egreso hospitalario con una sensibilidad del 68% y especificidad del 90%. La P. aeruginosa presentó resistencia a cefepime (36.6% y a aztreonam (34.1%, mientras que la letalidad global fue del 26.8%. Conclusión: El sexo masculino, la coexistencia de anemia, trombocitopenia, y neutropenia febril, así como la estancia en la unidad de cuidados intensivos aumentan la mortalidad en los pacientes oncológicos infectados con P. aeruginosa
Full Text Available RESUMEN La rápida emergencia de la resistencia antimicrobiana debida a las BLEE tiene un impacto significativo en la salud pública. En los últimos 24 años ha suscitado un gran interés el conocimiento acerca de las BLEE, esta explosión de publicaciones abarca a todos los continentes y más de 30 países, actualmente es motivo de preocupación y se considera un problema de salud pública. Las BLEE son enzimas que producen los gram negativos y confieren resistencia a las penicilinas, a todas las cefalosporinas y al aztreonam, pero no a los carbapenems ni a las cefamicinas y la mayoría son inhibidas por el acido clavulanico. En general las BLEE son derivadas de TEM-1, TEM-2 y SHV-1, difieren entre si de sus progenitoras por unos escasos aminoácidos por lo que su filogenia es cercana. Son comúnmente encontradas en E.coli, Klebsiella sp, y P.mirabilis, no obstante, existen otras BLEE que difieren filogenéticamente de TEM y SHV, como las CTX-M, las carbapenemasas tipo OXA y las metalo-β-lactamasas VIM e IMP, típicamente encontradas en especies de P. aeruginosa, Serratia sp and Enterobacter sp. La producción de BLEE en los patógenos de importancia clínica es un problema serio en los pacientes hospitalizados debido a las implicaciones clínicas, terapéuticas y económicas. Las técnicas para la detección de las BLEE van de lo simple con aspectos fenotipicos hasta las pruebas complejas moleculares de geno-detección específica. El objetivo de esta revisión es discutir el impacto clínico y epidemiológico de las BLEE más prevalentes así como las técnicas para su detección y su seguimiento nosocomial.
Burgess, David S; Frei, Christopher R
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
Djeffal, Samia; Bakour, Sofiane; Mamache, Bakir; Elgroud, Rachid; Agabou, Amir; Chabou, Selma; Hireche, Sana; Bouaziz, Omar; Rahal, Kheira; Rolain, Jean-Marc
The aims of this study were to investigate Salmonella contamination in broiler chicken farms and slaughterhouses, to assess the antibiotic resistance profile in avian and human Salmonella isolates, and to evaluate the relationship between avian and human Extended Spectrum β-Lactamase (ESBL)-producing isolates. Salmonella was screened in different sample matrices collected at thirty-two chicken farms and five slaughterhouses. The human isolates were recovered from clinical specimens at the University Teaching Hospital of Constantine (UTH). All suspected colonies were confirmed by MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time OF light) and serotyped. Susceptibility testing against 13 antibiotics including, amoxicillin/clavulanic acid, ticarcillin, cefoxitin, cefotaxime, aztreonam, imipenem, ertapenem, gentamicin, amikacin, ciprofloxacin, colistin, trimethoprim/sulfamethoxazole and fosfomycin, was performed using the disk diffusion method on Mueller-Hinton agar. ESBL-production was screened by the double-disk synergy test and confirmed by molecular characterization using PCR (polymerase chain reaction) amplification and sequencing of ESBL encoding genes. Clonality of the avian and human strains was performed using the Multi Locus Sequencing Typing method (MLST). Forty-five isolated avian Salmonella strains and 37 human collected ones were studied. Five S. enterica serotypes were found in avian isolates (mainly Kentucky) and 9 from human ones (essentially Infantis). 51.11% and 26.6% of the avian isolates were resistant to ciprofloxacin and cefotaxime, respectively, whereas human isolates were less resistant to these antibiotics (13.5% to ciprofloxacin and 16.2% to cefotaxime). Eighteen (12 avian and 6 human) strains were found to produce ESBLs, which were identified as bla CTX-M-1 (n = 12), bla CTX-M-15 (n = 5) and bla TEM group (n = 8). Interestingly, seven of the ESBL-producing strains (5 avian and 2 human) were of the same ST (ST15) and
Soliman, Ahmed M; Ahmed, Ashraf M; Shimamoto, Toshi; El-Domany, Ramadan A; Nariya, Hirofumi; Shimamoto, Tadashi
Two Proteus mirabilis strains, designated PmTAN59 and PmKAF126, were isolated from two different Egyptian cities in 2014 and 2015, respectively. PmTAN59 was isolated from a sputum swab from a pneumonia patient in Tanta University Teaching Hospital. PmKAF126 was isolated from a patient with a diabetic foot infection in a hospital in the city of Kafr El-Sheikh. The two isolates were identified with bacterial small ribosomal RNA (16S rRNA) gene amplification and sequencing and tested for antimicrobial sensitivity with a Kirby-Bauer disk diffusion assay. The two strains were resistant to amoxicillin/clavulante, ampicillin, cefotaxime, cefoxitin, ceftriaxone, chloramphenicol, ciprofloxacin, colistin, gentamicin, kanamycin, nalidixic acid, spectinomycin, streptomycin, sulfamethoxazole/trimethoprime, and tetracycline, but sensitive to aztreonam, imipenem, and meropenem. Molecular characterization was used to map the entire backbone, including the multiple antibiotic resistance (MDR) region, of Salmonella genomic island 1 (SGI1). Both isolates carried a structure similar to SGI1, with two different MDR regions corresponding to SGI1-PmABB in PmTAN59 and SGI1-W in PmKAF126. SGI1-PmABB carried an integron of ~1.5kb with a two-gene cassette, aacCA5-aadA7, which confers resistance to gentamicin, streptomycin, and spectinomycin, whereas SGI1-W carried an integron of ~1.9kb containing aadA2-lnuF, which confers resistance to spectinomycin, streptomycin, and lincosamides. PmKAF126 carried the entire SGI1 sequence, however PmTAN59 carried a SGI1 structure with a deletion in the region from ORF S005 to ORF S009 and accompanied by insertion of IS1359 (1258bp). Furthermore, PmTAN59 carried class 2 integron of ~2.2kb containing dfrA1-sat2-aadA1. An ERIC-PCR analysis detected no clonal relationship between the two strains. Molecular screening for other antimicrobial resistance genes and a plasmid analysis indicated that PmTAN59 carried an IncFIB plasmid type. This strain also carried bla
Pseudomonas aeruginosa: freqüência de resistência a múltiplos fármacos e resistência cruzada entre antimicrobianos no Recife/PE Pseudomonas aeruginosa: frequency of resistance to multiple drugs and cross-resistance between antimicrobials in Recife/PE
Eduardo Andrada Pessoa de Figueiredo
Full Text Available JUSTIFICATIVA E OBJETIVOS: A multi-resistência bacteriana tem crescido significativamente nos últimos anos. Entre os gram-negativos a P. aeruginosa demonstra maior facilidade de desenvolvimento de resistência aos antibióticos. O objetivo deste estudo foi determinar os padrões de susceptibilidade antimicrobiana, freqüência de resistência a múltiplos fármacos e de resistência cruzada entre antimicrobianos das cepas de Pseudomonas aeruginosa. MÉTODO: O estudo foi realizado entre setembro de 2004 e janeiro de 2006. Os testes de susceptibilidade antimicrobiana foram realizados em 304 cepas de P. aeruginosa segundo os padrões do National Committee for Clinical and Laboratory Standards (NCCLS. RESULTADOS: Os materiais mais freqüentes foram urina com 26,7% e secreção traqueal com 26,1%. Os seguintes antibióticos, com respectivos percentuais de susceptibilidade, foram observados: piperacilina-tazobactam (66,2%; aztreonam (59,8%; amicacina (59,4%; meropenem (58,2%; imipenem (57,7%; ciprofloxacina (49,7%; gentamicina e cefepima (48,6%; ceftazidima (30% e cefotaxima (6,8%. Detectou-se elevada prevalência de multi-resistência, com 49,7% das cepas resistentes a três antibióticos ou mais e 28% resistentes a seis antibióticos ou mais. Adicionalmente se demonstraram taxas de resistência cruzada entre os beta-lactâmicos (carbapenêmicos e piperacilina/tazobactam e os aminoglicosídeos e quinolonas entre 22,9% e 38,1% (fármacos comumente utilizados como adjuvantes no tratamento das infecções graves por pseudomonas, refletindo dificuldade nas opções de associação de antimicrobianos para tratamentos combinados. CONCLUSÕES: A freqüência de cepas multi-resistentes de P. aeruginosa foi semelhante à descrita na literatura nacional e maior do que a mundial. Para reduzir a freqüência destes clones multi-resistentes, monitorização epidemiológica e racionalização de antimicrobianos devem ser implementadas urgentemente.BACKGROUND AND
. Determination of B-lactamase and AmpC-B-lactamase enzyme production were carried out by two methods. Cefotaxime, ceftazidime, cefoperazone, cefoxitin and aztreonam were used with and without amoxycillin clavulanic acid to detect the presence of extended-spectrum B-lactamase (ESBL) harbouring isolates by using double-disk diffusion synergy test (DDST). Combined disk method was used also to detect the presence of ESBL harbouring isolates by using cefoperazone (CFP) and cefoperazone sulbactam (SCF) among the tested strains. Agar dilution method was used to determine minimum inhibitory concentration (MIC) of ampicillin sulbactam, cefoperazone, gentamycin and levofloxacin alone and in combination (Ampicillin sulbactam with both of gentamycin and levofloxacin) and (cefoperazone with both of gentamycin and levofloxacin). Fractional inhibitory concentration (FIC) for the combined antibiotics were calculated according to checkerboard method and synergistic effect were determined. Some resistant isolates were subjected to molecular studies including plasmid profile (Kleb.52 Morg.60 and Ps.72 ) by using a high pure plasmid isolation kit and protein pattern of Ps.72 before and after irradiation in the presence of different antibiotics alone (cefoperazone, gentamycin and ampicillin sulbactam) or in combined (cefoperazone with gentamycin and ampicillin sulbactam with gentamycin)The result of the present investigation showed that, 9 multi-drug resistant isolates were identified as; 2 isolates Escherichia coli, 2 isolates Pseudomonas aeruginosa, 1 isolate Citrobacter freundii, 1 isolate Morganella morganii all were isolated from urine samples
Toval, Francisco; Guzmán-Marte, Anel; Madriz, Vivian; Somogyi, Teresita; Rodríguez, César; García, Fernando
This study aimed to assess the molecular basis of the resistance to carbapenems in clinical isolates of Pseudomonas aeruginosa recovered from a tertiary-level health facility in San José, Costa Rica. A total of 198 non-duplicated isolates were evaluated for their susceptibility to β-lactams, aminoglycosides and fluoroquinolones. The production of metallo-β-lactamases (MBLs), the presence of MBL encoding genes (blaIMP, blaVIM and blaGIM-1) and the occurrence of these genes within class 1 integrons were investigated. In addition, an ERIC2 PCR fingerprinting method was used to elucidate the distribution of the detected MBL genes within the strain collection. Of the 198 isolates tested, 125 (63.1 %) were categorized as carbapenem-resistant. The majority (88.8 %) of the carbapemen-resistant isolates also showed resistance to ceftazidime, cefepime, aztreonam, ticarcillin/clavulanic acid, amikacin, gentamicin, tobramycin, ciprofloxacin and gatifloxacin. Among the carbapenem-resistant isolates, 102 (81.6 %) showed MBL activity. Strikingly, both blaIMP and blaVIM genes were simultaneously detected in most (94.1 %) of the 102 MBL producers. Five carbapenem-resistant MBL producers were positive only for blaIMP genes. Almost 70 % of the isolates examined harboured the intI1 gene, accompanied by the sul1 and qacEΔ1 genes in 136 (99 %) and 122 (89 %) isolates, respectively. The majority (94.4 %) of the carbapenem-resistant isolates carried the intI1 gene, in contrast to 26 % of the carbapenem-susceptible isolates. Ninety-three out of 96 (96.9 %) isolates carrying both blaIMP and blaVIM genes also harboured the intI1, sul1 and qacEΔ1 genes. Gene cassettes from carbapenem-susceptible and MBL-negative carbapenem-resistant isolates encoded aminoglycoside-resistance enzymes (aadA2, aadA4 and aadA6) as well as orfD and qacF genes. RAPD analysis distributed 126 of the isolates in 29 clusters. Eighty of the 90 blaIMP (+) blaVIM (+) isolates were sorted into 16
Nada, H M.AL.M. [National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)
. Determination of B-lactamase and AmpC-B-lactamase enzyme production were carried out by two methods. Cefotaxime, ceftazidime, cefoperazone, cefoxitin and aztreonam were used with and without amoxycillin clavulanic acid to detect the presence of extended-spectrum B-lactamase (ESBL) harbouring isolates by using double-disk diffusion synergy test (DDST). Combined disk method was used also to detect the presence of ESBL harbouring isolates by using cefoperazone (CFP) and cefoperazone sulbactam (SCF) among the tested strains. Agar dilution method was used to determine minimum inhibitory concentration (MIC) of ampicillin sulbactam, cefoperazone, gentamycin and levofloxacin alone and in combination (Ampicillin sulbactam with both of gentamycin and levofloxacin) and (cefoperazone with both of gentamycin and levofloxacin). Fractional inhibitory concentration (FIC) for the combined antibiotics were calculated according to checkerboard method and synergistic effect were determined. Some resistant isolates were subjected to molecular studies including plasmid profile (Kleb.52 Morg.60 and Ps.72 ) by using a high pure plasmid isolation kit and protein pattern of Ps.72 before and after irradiation in the presence of different antibiotics alone (cefoperazone, gentamycin and ampicillin sulbactam) or in combined (cefoperazone with gentamycin and ampicillin sulbactam with gentamycin)The result of the present investigation showed that, 9 multi-drug resistant isolates were identified as; 2 isolates Escherichia coli, 2 isolates Pseudomonas aeruginosa, 1 isolate Citrobacter freundii, 1 isolate Morganella morganii all were isolated from urine samples.
Ibonne Aydee García Romero
Full Text Available Antecedentes. Las enterobacterias, antaño flora normal del tracto gastrointestinal, han cambiado su biología y emergido como agentes patógenos nosocomiales que se tornan resistentes los antibióticos conocidos. Objetivo. Realizar la caracterización epidemiológico-molecular de 20 aislamientos de Enterobacter cloacae resistentes a cefalosporinas de tercera generación; provenientes de un hospital de tercer nivel de Bogotá-Colombia. Material y métodos. Los aislamientos fueron identificados mediante sistemas automatizados Microscan y VITEK, se utilizó el Enterobacter asbureae como control externo inter-especie. La confirmación de resistencia se hizo por técnica de difusión en agar, y una vez establecida se realizó BLEE para comprobación. La determinación de puntos isoeléctricos se hizo, mediante lisis por ultrasonido y la genotipificación mediante la metodología para bacterias Gramnegativas propuesta por Versalovic. Resultados: Los aislamientos colectados durante un año fueron causantes de 15 casos de infección Intrahospitalaria y dos colonizaciones. Todos los aislamientos presentaron resistencia a cefotaxima, ceftazidima, ceftriaxona, aztreonam y ciprofloxacina, 95% a amikacina, gentamicina y cloranfenicol, 75% a trimetoprim/sulfametoxazol, 20% a cefepime y todos fueron sensibles a imipenem. Dos aislamientos fueron confirmados como productores de â-lactamasas de espectro extendido (BLEE por la técnica microbiológica de disco combinado. Por isoelectroenfoque presentaron dos â-lactamasas con puntos isoeléctricos (pI de 5,4 y 8,2. En los 18 aislamientos no inhibidos por ácido clavulánico, se detectaron entre 2 y 4 â-lactamasas con pI de 5,4; 6,0; 7,0; 8,2 y mayor que 8,2; la resistencia a cefalosporinas de tercera generación podría ser atribuida a la hiperproducción de AmpC; los valores de pI sugieren la producción simultánea de â-lactamasas tipo SHV y TEM. La genotipificación mediante tres metodologías de rep
[Evolution of susceptibility to antibiotics of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumanii, in a University Hospital Center of Beirut between 2005 and 2009].
Hamouche, E; Sarkis, D K
Until recently, multiresistant bacteria were only limited to hospitals. However, they are now responsible for community acquired infections, affecting people who have had no contact with the hospital environment. Several mechanisms are associated with these resistances. The production of betalactamases is however the predominant mechanism and especially the production of extended spectrum beta-lactamases or ESBL by strains of Escherichia coli and Klebsiella pneumoniae, which mediate resistance to third generation cephalosporins and aztreonam (AZT). The association of multiple mechanisms of resistance (efflux pumps, impermeability and enzymatic inactivation) generates multi resistant bacteria such as Pseudomonas aeruginosa MDR and Klebsiella pneumoniae MDR. The aim of the study was to analyze retrospectively the susceptibility to antibiotics of strains of E. coli, K. pneumoniae, P. aeruginosa and A. baumanii isolated from hospitalized and outpatients in a university hospital center of Beirut over a period of five years from 2005 to 2009. Bacterial strains were classified according to their origin (inpatients versus outpatients), their ability to produce or not ESBLs for E. coli and K. pneumonia and if they were MDR for P. aeruginosa and A. baumanii. Antibiotics susceptibilities were retrieved from the informatics database of the hospital. Comparison of susceptibility percentages was done using a unilateral z-test on a computer program. In 2009, 2541 strains of E. coli were isolated, 773 of which or 30.4 % were ESBL producers while 2031 strains were isolated in 2005, of which 361 or 17.8 % were ESBL producers (pproducing strains between 2007 and 2009: 33.4 % versus 30.4 % (p=0.03). Among 560 strains of K. pneumoniae isolated in 2009, 178 strains or 31.8 % were ESBL producers in comparison to 23.7 % of the strains isolated in 2005 (p=0.03). We also noticed a decrease in hospital strains susceptibility to piperacilline-tazobactam (TZP), cefotaxime (CTX
Chorro-Mari, Veronica; Christiansen, Nanna
Due to national changes to the commissioning process of high cost nebulisers (HCN) for Cystic Fibrosis (CF) patients, CF centres have to repatriate the prescribing of the HCN to the tertiary care centres.1 The following nebulisers will no longer be prescribed by primary care: Cayston® (Aztreonam); Colomycin®, Pomixin®, Clobreathe® (Colistimethate); Pulmozyme® (Dornase alfa); Tobi®, Tobi Podhaler ®, Bramitob® (Tobramycin).This abstract explains how the Royal London Hospital (RLH) Paediatric Pharmacy recruited over 100 paediatric (CF) patients smoothly within a period of 4 months and set up a homecare system to avoid patients and families having to travel large distances to obtain their medication. A number of homecare companies were evaluated initially. Parameters looked at were reports of customer satisfaction, delivery cost, turn-around time once the prescription was received and availability of same day delivery service.In order to capture existing patients we met with CF Specialist Nurses to establish the total number of patients on HCN, what nebulised treatment they were on and their respective doses. We prioritised patients that had known problems with GP prescribing and anybody newly starting on HCN.To communicate the change to parents, a letter was sent to all parents explaining the changeover to homecare delivery and tertiary prescribing. In addition a section in the parent bulletin was dedicated to the topic as well. Following this we contacted parents via phone and in clinic to request consent and explain the process.Up to 10 patients were contacted weekly (average of 7); the consent form and registration form were then faxed to the Homecare company for patient registration. In parallel to this prescriptions were requested for the patients that had been set up in the previous week, ensuring that prescribing was spread out over time to avoid having peak times for repeat prescriptions.In addition to the letter to parents GP surgeries were also
Full Text Available Klebsiella pneumoniae carbapenemase (KPC was detected in two isolates of carbapenem-resistant K. pneumoniae in an italian teaching hospital. This is the first report of a KPC-producing isolates in our country. The first strain was isolated from a urine sample collected from a indwelling urinary catheter in a ICU-patient with subdural haematoma, while the second was from the culture of the central venous catheter (CVC in a patient affected by Crohn’s disease admitted in gastroenterology ward. Both were resistant to all ß-lactams, susceptible to imipenem and meropenem and resistant to ertapenem.They were resistant to other classes of non-ß-lactams antibiotics such as quinolones, aminoglycosides (with the exception of amikacin, trimethoprim-sulfamethoxazole (TMP-SMX as well as to nitrofurantoin.The isolates were not associated with travel abroad.They were found to contain the plasmid encoded carbapenemase gene blaKPC and were also positive to the Hodge’s test.The detection of KPC-producing bacteria has important implications in infection control and public health. The K. pneumoniae carbapenemase (KPC belong to class A ß-lactamases of the functional group 2f. Reported for the first time in U.S. in 2001, these agents were subsequently identified in Europe. KPC strains are typically resistant to penicillins, extended-spectrum cephalosporin and aztreonam and present a peculiar behavior against carbapenems in that MIC is close to the susceptibility value or is borderline (except for ertapenem.This pattern is often associated with resistance to quinolones.The information is conveyed by the resistance plasmids, thus explaining their diffusion and implication in outbreaks of KPC. Despite this, to date there are few reports concerning the isolation of this phenotype in Italy.The purpose of this paper is to present two clinical cases related to the isolation of KPC in our hospital. The KPC-producing strains have been respectively isolated: the first
pneumoniae, Staphylococcus hominis, Candida spp. (5,4±3,0%. 2. The most effective antibacterial drug is meropenem. 78,7% of all isolates have sensitivity to it. The sensitivity to gatifloxacin have 73,7%; to tigecycline 71,1%; to amikacin – 67,3%, to moxifloxacin – 59,6% of cultures, to two agents (levofloxacin and pefloxacin – 55,8% of cultures respectively. 3. 100% of the family Micrococcaceae isolates were resistant to benzylpenicillin, 95,8% - to ampicillin, 87,5% - to amoxicillin and cefuroxime, 83,3% - to azithromycin, erythromycin and lincomycin. Members of the Streptococcaceae family were resistant to cefuroxime. 100% of the family Enterobacteriaceae isolates had no sensitivity to carbenicillin, 87,5% of isolates - to cefuroxim and gentamicin, 81,2% - to amoxicillin and ampicillin, 75,0% - to cefazolin, 50,0% - to ceftriaxonum and aztreonam. 4. Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter haemolyticus isolates were multi-drug resistant.