In-Vitro Activity of Doripenem vs. Imipenem & Meropenem against Clinical Isolates of Pseudomonas and Other Oxidase-Positive Gram- Negative Bacilli (original) (raw)
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Antibiotics, 2021
The emergence of antibiotic resistance has severely impaired the treatment of chronic respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Since the reintroduction of polymyxins as a last-line therapy against MDR Gram-negative bacteria, resistance to its monotherapy and recurrent infections continue to be reported and synergistic antibiotic combinations have been investigated. In this study, comprehensive in vitro microbiological evaluations including synergy panel screening, population analysis profiling, time-kill kinetics, anti-biofilm formation and membrane damage analysis studies were conducted to evaluate the combination of polymyxin B and meropenem against biofilm-producing, polymyxin-resistant MDR P. aeruginosa. Two phylogenetically unrelated MDR P. aeruginosa strains, FADDI-PA060 (MIC of polymyxin B [MICpolymyxin B], 64 mg/L; MICmeropenem, 64 mg/L) and FADDI-PA107 (MICpolymyxin B, 32 mg/L; MICmeropenem, 4 mg/L) were investigated. Genome sequenc...
Clinical Microbiology and Infection, 2006
In total, 54 731 Gram-negative bacilli isolated worldwide between 2001 and 2004 from diverse sites of infection were tested for susceptibility to polymyxin B by the broth reference microdilution method, with interpretation of results according to CLSI (formerly NCCLS) guidelines. Polymyxin B showed excellent potency and spectrum against 8705 Pseudomonas aeruginosa and 2621 Acinetobacter spp. isolates (MIC50, ≤ 1 mg/L and MIC90, 2 mg/L for both pathogens). Polymyxin B resistance rates were slightly higher for carbapenem-resistant P. aeruginosa (2.7%) and Acinetobacter spp. (2.8%), or multidrug-resistant (MDR) P. aeruginosa (3.3%) and Acinetobacter spp. (3.2%), when compared with the entire group (1.3% for P. aeruginosa and 2.1% for Acinetobacter spp.). Among P. aeruginosa, polymyxin B resistance rates varied from 2.9% in the Asia-Pacific region to only 1.1% in Europe, Latin America and North America, while polymyxin B resistance rates ranged from 2.7% in Europe to 1.7% in North America and Latin America among Acinetobacter spp. Polymyxin B also demonstrated excellent activity (MIC90, ≤ 1 mg/L; > 98% susceptible) against Citrobacter spp., Escherichia coli and Klebsiella spp., but activity was more variable against Enterobacter spp. (MIC50, ≤ 1 mg/L; 83.3% susceptible) and Stenotrophomonas maltophilia (MIC50, ≤ 1 mg/L; 72.4% susceptible), and was very limited (MIC50, > 8 mg/L) against Burkholderia cepacia (11.8% susceptible), Serratia spp. (5.4% susceptible), indole-positive Proteus spp. (1.3% susceptible) and Proteus mirabilis (0.7% susceptible).
European Journal of Clinical Microbiology & Infectious Diseases, 2005
Multidrug-resistant strains of Pseudomonas aeruginosa have become increasingly problematic in certain hospitals. For a 3-month period in 2001, all unique patient isolates were collected from 15 hospitals in Brooklyn, New York, USA. Of 691 isolates, only 70% were susceptible to imipenem and 56% to ciprofloxacin. These susceptibility rates were lower than those found in a prior surveillance study in 1999 (76% and 71% susceptible to imipenem and ciprofloxacin, respectively; p<0.001). The rate of imipenem resistance was associated with fluoroquinolone usage at each hospital (p=0.04). All isolates were susceptible to polymyxin B and 95% to amikacin. Among 195 imipenem-resistant isolates, 47 unique ribotypes were found. However, four ribotypes accounted for >50% of isolates and were shared by most hospitals. Time-kill studies with 13 unique multiresistant strains revealed that polymyxin B was bactericidal against all strains at 4 mg/l, but only against 3 of 13 (23%) strains at 2 mg/l. Using 2 mg/l, significant bacterial regrowth was evident for 5 of 13 (38%) strains. The addition of azithromycin to polymyxin B (2 mg/l) produced a mean decrease of 1 log cfu/ml greater than polymyxin alone and allowed bacterial regrowth in only 2 of 13 (15%) strains. Multiresistant P. aeruginosa is highly endemic to this city, with a few strains having spread among most hospitals. Polymyxin B remains active against all isolates and produces concentration-dependent killing in vitro. Azithromycin appears to enhance the in vitro activity of polymyxin B. The clinical utility of this combination remains to be established.
Antimicrobial Agents and Chemotherapy, 2015
There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistantAcinetobacter baumanniiorPseudomonas aeruginosaisolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severeA. baumanniiorP. aeruginosainfections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lackingin vitroactivity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P= 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups...
BACKGROUND AND OBJECTIVE Doripenem is a new parenteral carbapenems, which has beta-lactamase stability and is not inactivated by renal dehydropeptidases. Doripenem has a spectrum of activity similar to imipenem and ertapenem against Gram-positive cocci and similar to meropenem against Gram-negative pathogens. In this study, we summarize the activity of doripenem against Gram negative bacilli in comparison with other carbapenems (Imipenem, meropenem) and select group of antimicrobial drugs by disk diffusion.
Annals of Clinical Microbiology and Antimicrobials
Annals of Clinical …, 2009
Background: Considering the increasing use of polymyxins to treat infections due to multidrug resistant Gram-negative in many countries, it is important to evaluate different susceptibility testing methods to this class of antibiotic.
Polymyxin B for Gram Negative Multidrug Resistant Bacteria in a Hispanic Population
Puerto Rico health sciences journal, 2019
OBJECTIVE This study intends to determine the prevalence of multidrug resistant (MDR) infections by A. baumannii, K. pneumoniae and P. aeruginosa in a tertiary care teaching hospital intensive care unit (ICU) in San Juan, PR, estimate the mortality rate and compare the morbidity and mortality differences among those treated with and without polymyxin B. METHODS We selected adults patients admitted to the ICU who had positive cultures from January 2012 to June 2013. Sample consisted of 25 patients with age ranges from 27-78 years, 13 women and 12 men. RESULTS The median age at death was 60 years. Polymyxin B nephrotoxicity was identified on 15% of the patients. Variables related to higher survival were younger age, female sex, use of polymyxin B, and the use of daptomycin. The use of vancomycin and vasopressors were associated with worse outcome. Mortality associated to single MDR bacteria was 88% for A. baumannii, 84% for K. pneumoniae and 67% for P. aeruginosa. All patients with mo...
Clinical Microbiology and Infection, 2019
Objectives: Polymyxins have been revitalized to combat carbapenem-resistant Enterobacteriaceae (CRE). However, evaluating the activity of these agents by traditional broth dilution methods is not practical for busy clinical laboratories. We compared polymyxin B activity using two quantitative susceptibility testing methods, Etest ® and broth microdilution (BMD), against CRE isolates from patients at an academic medical centre. Methods: Polymyxin B activity against 70 CRE clinical isolates was determined by Etest ® according to the manufacturer and by BMD according to CLSI guidelines. Pseudomonas aeruginosa ATCC ® 27853 and Escherichia coli NCTC 13846 served as quality control strains. The EUCAST colistin susceptibility breakpoint of Enterobacteriaceae (2 mg/L) was used. Essential agreement was isolates with an MIC within 1 log 2 dilution over total isolates. Categorical agreement was number of isolates in the same susceptibility category (susceptible or resistant) over total isolates. Major and very major error rates were calculated using number of susceptible and number of resistant isolates, respectively, as the denominator. McNemar's test was used for determining a difference in susceptibility between methods. Results: The CRE isolates were primarily Klebsiella spp. (49%) and Enterobacter spp. (36%). Polymyxin B susceptibility was significantly higher by Etest ® compared with BMD (97% versus 77%; p 0.0001). Categorical agreement was 80%, but essential agreement was low (10%). False non-susceptibility was never observed by Etest ® (BMD reference), but the very major errors were high (88%). Conclusions: Etest ® reporting of false susceptibility may result in inappropriate antibiotic use and treatment failure clinically. We do not recommend using Etest ® for polymyxin B susceptibility testing for routine patient care.