non-ICU Isolates Research Articles

Ceftazidime/avibactam tested against Gram-negative bacteria from intensive care unit (ICU) and non-ICU patients, including those with ventilator-associated pneumonia

Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler classes A, C and some D enzymes. Clinical isolates were collected from 71 US medical centres in 2012–2013 and were tested for susceptibility at a central laboratory by reference broth microdilution methods. Results for 4381 bacterial isolates from intensive care unit (ICU) patients as well as those from ventilator-associated pneumonia (VAP) (n=435) were analysed and compared with those of 14 483 organisms from non-ICU patients. β-Lactamase-encoding genes were evaluated for 966 Enterobacteriaceae by a microarray-based assay. Ceftazidime/avibactam was active against 99.8/100.0% of Enterobacteriaceae (MIC90, 0.25/0.25mg/L) from ICU/non-ICU patients (2948/10,872 strains), including isolates from VAP (99.1%), multidrug-resistant (MDR) strains (99.3%), extensively drug-resistant (XDR) strains (96.5%) and meropenem-non-susceptible strains (98.0%), at MICs of ≤8mg/L. Against Enterobacteriaceae, susceptibility rates for ceftazidime, piperacillin/tazobactam and meropenem (ICU/non-ICU) were 86.1/91.8%, 88.0/94.3% and 97.8/99.2%, respectively. Meropenem was active against 75.1/85.4% of MDR Enterobacteriaceae and 8.1/27.1% of XDR Enterobacteriaceae from ICU/non-ICU patients. When tested against Pseudomonas aeruginosa, ceftazidime/avibactam inhibited 95.6/97.5% of isolates from ICU/non-ICU (842/2240 isolates), 97.3% of isolates from VAP, 80.7% of ceftazidime-non-susceptible and 80.7% of MDR isolates at ≤8mg/L. Susceptibility rates for P. aeruginosa from ICU/non-ICU were 77.7/86.9% for ceftazidime, 71.2/82.2% for piperacillin/tazobactam and 76.6/84.7% for meropenem. In summary, lower susceptibility rates were observed among ICU compared with non-ICU isolates. Ceftazidime/avibactam exhibited potent activity against a large collection of Gram-negative organisms from ICU and non-ICU patients and provided greater coverage than currently available β-lactams.

Increase in the Prevalence of Carbapenem-Resistant Acinetobacter Isolates and Ampicillin-Resistant Non-Typhoidal Salmonella Species in Korea: A KONSAR Study Conducted in 2011.

BackgroundAntimicrobial surveillance is important for providing an up-to-date understanding of the epidemiology of antimicrobial resistance and for creating a forum for rational drug development. In this study, we analyzed antimicrobial test data generated in 2011 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program (KONSAR).Materials and MethodsData on the results of susceptibility tests conducted in 32 hospitals and two commercial laboratories were analyzed. Data on isolates from patients admitted to an intensive care unit (ICU) and those admitted to other wards were compared. Intermediate susceptibility was not analyzed and duplicate isolates were excluded.ResultsEscherichia coli was the most prevalent organism identified in both the hospital and commercial laboratories. Among the hospital isolates, methicillin-resistant Staphylococcus aureus (MRSA), penicillin G-non-susceptible Streptococcus pneumoniae, and ampicillin-resistant Enterococcus faecium remained as prevalent as they were in 2009. The proportion of vancomycin-resistant E. faecium (VR-EFM) slightly decreased from 29% in 2009 to 23% in 2011. Resistance rates of Klebsiella pneumoniae to ceftazidime, cefoxitin, fluoroquinolone, and amikacin were 24%, 14%, 27%, and 8%, respectively. Resistance rates of Pseudomonas aeruginosa to fluoroquinolone, ceftazidime, imipenem, and amikacin were 33%, 20%, 22%, and 16%, respectively, whereas those of Acinetobacter spp. resistance were 71%, 66%, 64, and 51%, respectively. The prevalence of oxyimino-cephalosporin-resistant E. coli and K. pneumoniae, carbapenem-resistant Acinetobacter spp. and P. aeruginosa, MRSA, and VR-EFM among ICU isolates was higher than those among non-ICU isolates. Extended-spectrum β-lactamase-producing E. coli and K. pneumoniae, imipenem-resistant P. aeruginosa, and VR-EFM were more prevalent among isolates from commercial laboratories than those from hospitals. Resistance rates of K. pneumoniae to ceftazidime and amikacin decreased from 32% and 24% in 2005 to 24% and 8% in 2011, respectively. The resistance rate of P. aeruginosa to amikacin decreased from 22% in 2005 to 16% in 2011. The proportion of imipenem-resistant Acinetobacter spp. increased from 16% in 2005 to 64% in 2011.ConclusionsThe prevalence of MRSA, penicillin G-non-susceptible S. pneumoniae, and ampicillin-resistant E. faecium among clinical isolates tested in laboratories remained high. Multidrug resistance was more prevalent among isolates from ICUs. The prevalence of ceftazidime-resistant and amikacin-resistant K. pneumoniae and amikacin-resistant P. aeruginosa decreased after 2005, while the prevalence of imipenem-resistant Acinetobacter spp. increased.

Recent Trends in Antimicrobial Resistance in Intensive Care Units in Korea

Background: In general, higher resistance rates are observed among intensive care unit (ICU) isolates than non-ICU isolates. In this study, resistance rates of isolates from ICUs and non-ICUs were compared using the data generated from 20 hospitals in Korea. Methods: Susceptibility data were collected from 20 hospitals participating in the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) program. Duplicate isolates were excluded from the analysis. The resistance rates did not include intermediate susceptibility. Results: The most prevalent bacteria in the ICUs were Staphylococcus aureus (21%) and Acinetobacter spp. (19%), and those in non-ICU were Escherichia coli (27%) and S. aureus (14%). The resistance rates were higher in ICUs than in non-ICUs at 84% and 58% for methicillin-resistant S. aureus, 86% and 70% for methicillin-resistant coagulase-negative Staphylcoccus (CNS), 34% and 19% for vancomycin-resistant Enterococcus faecium, 38% and 19% for cefotaxime-resistant E. coli, 45% and 25% for cefotaxime-resistant Klebsiella pneumoniae, 42% and 24% for ceftazidime-resistant Enterobacter cloacae, 29% and 11% for ceftazidime-resistant Serattia marcescens, 83% and 44% for imipenem-resistant Acinetobacter spp., and 32% and 17% for imipenem-resistant Pseudomonas aeruginosa, respectively. Conclusion: The most prevalent bacteria in ICUs were S. aureus, CNS, and Acinetobacter spp., and high multi-drug resistance rates were observed in the Acinetobacter isolates. Therefore, infection control should be practiced in ICUs to prevent infections caused by multi-drug resistant bacteria.

Comparative activity of carbapenem testing (the COMPACT study) in Turkey

BackgroundRecent evidence indicates that Gram-negative bacterial pathogens, the most common of which are Pseudomonas spp., Enterobacteriaceae, and Acinetobacter baumannii, are frequent causes of hospital-acquired infections. This study aims to evaluate the in vitro activity of doripenem and comparator carbapenem antibiotics against Gram-negative clinical isolates collected from COMParative Activity of Carbapenem Testing (COMPACT) study centres in Turkey.MethodsTen centres in Turkey were invited to submit Pseudomonas aeruginosa, Enterobacteriaceae, and other Gram-negative isolates from intensive care unit (ICU)/non-ICU patients with complicated intra-abdominal infections, bloodstream infections, or nosocomial pneumonia, including ventilator-associated pneumonia, between May and October 2008. Susceptibility was determined by each centre using E-test. A central laboratory performed species confirmation as well as limited susceptibility and quality-control testing.ResultsFive hundred and ninety six isolates were collected. MIC90 values for doripenem, meropenem, and imipenem, respectively, were 32, ≥ 64, and ≥ 64 mg/L against Pseudomonas spp.; 0.12, 0.12, and 0.5 mg/L against Enterobacteriaceae; and ≥ 64 mg/L for each against other Gram-negative isolates. In determining the susceptibility of hospital isolates of selected Gram-negative pathogens to doripenem, imipenem, and meropenem, we found that against all pathogens combined, the MIC90 for ICU compared with non-ICU isolates was higher.ConclusionsDoripenem showed similar or slightly better activity than meropenem and better activity than imipenem against the Gram-negative pathogens collected in Turkey.

Comparative Activity of Carbapenem Testing (COMPACT) study in Germany

The aim of this study was to determine the current susceptibility of hospital isolates of contemporary Gram-negative pathogens to the carbapenems doripenem, imipenem and meropenem. Between May and October 2008, seven centres in Germany were invited to collect and submit Pseudomonas aeruginosa, Enterobacteriaceae and other Gram-negative bacterial Intensive Care Unit (ICU)/non-ICU isolates from patients with complicated intra-abdominal infections (cIAIs), bloodstream infections (BSIs) or nosocomial pneumonia (NP). Susceptibility was determined at each centre by Etest. A central laboratory performed species confirmation as well as limited susceptibility and quality control testing. In total, 363 isolates were collected, comprising 46.0% Enterobacteriaceae, 45.2% P. aeruginosa, 4.7% Acinetobacter spp. and 4.1% other Gram-negatives. Most isolates (47.9%) were collected from NP, 32.8% were from cIAIs and 19.3% from BSIs; 57.3% were obtained from ICU patients. The MIC90 values (minimum inhibitory concentration for 90% of the isolates) for doripenem, meropenem and imipenem were, respectively, 4, 16 and 32mg/L against P. aeruginosa, 0.06, 0.06 and 0.5mg/L against Enterobacteriaceae and ≥64mg/L for each carbapenem against other Gram-negative isolates. Using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 81.1%, 75.6% and 79.3% of P. aeruginosa were susceptible to doripenem, imipenem and meropenem, respectively. Against all pathogens combined, MIC90 values for ICU versus non-ICU isolates, respectively, were 4mg/L vs. 1mg/L for doripenem, 8mg/L vs. 1mg/L for meropenem and ≥64mg/L vs. 8mg/L for imipenem. Doripenem showed comparable activity against P. aeruginosa from patients with BSIs, cIAIs or NP. Similar findings were observed for Enterobacteriaceae and other Gram-negatives, including Acinetobacter spp. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against Gram-negative pathogens collected in Germany.

Changes in MIC Within a Global Collection of Acinetobacter baumannii Collected as Part of the Tigecycline Evaluation and Surveillance Trial, 2004 to 2009

BackgroundThe Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) began in 2004 to monitor global antimicrobial susceptibility to tigecycline and a range of comparator antimicrobials among gram-positive and gram-negative organisms. ObjectiveThe aim of this study was to report changes in MIC for tigecycline and other antimicrobial agents among 10,149 Acinetobacter baumannii isolates collected globally between 2004 and 2009. MethodsMICs of 10,149 isolates were determined locally using Clinical Laboratory and Standards Institute (CLSI) methodologies. Antimicrobial susceptibility was ascertained according to CLSI interpretive criteria (no interpretive criteria have been approved for tigecycline against Acinetobacter spp). ResultsIncreases in resistance were noted for most antimicrobial agents in all regions. Significant (P < 0.05) increases in percentage resistance were reported for all antimicrobial agents globally. The smallest changes in cumulative geometric mean MICs were reported for tigecycline (0.2 mg/L) and cefepime (3.5 mg/L). MIC90s were at the top of their testing ranges for most agents against both multidrug-resistant (MDR) and non-MDR isolates; only tigecycline showed little change in MIC90 between MDR (2 mg/L) and non-MDR (1 mg/L) isolates. Resistance was higher among isolates from the intensive care unit (ICU) compared with non-ICU isolates. ConclusionThese findings suggest that resistance is increasing among clinical isolates of A baumannii globally. Although resistance to tigecycline has been reported in the treatment of infections caused by A baumannii, it retains in vitro activity against this pathogen.

CXA-201 Effective against Common ICU Pathogens, Including MDR Gram-Negative Pathogens and Pseudomonas aeruginosa

Using a pharmacokinetic/pharmacodynamic (PK/PD) target algorithm, the in vitro potency of CXA-201 (CXA101/tazobactam), a novel cephalosporin and b-lactamase inhibitor combination that is being developed to treat serious bacterial infections, was reported to be lower in isolates from the intensive care unit (ICU) compared with non-ICU isolates.

Pharmacodynamic evaluation of i.v. antimicrobials againstPseudomonas aeruginosasamples collected from U.S. hospitals

Selected i.v. antimicrobials were evaluated against Pseudomonas aeruginosa isolates collected from U.S. hospitals to predict the likelihood of achieving maximal bactericidal activity. The pharmacodynamic profiles of ceftazidime, doripenem, imipenem-cilastatin, levofloxacin, meropenem, and piperacillin-tazobactam were simulated for 5000 adult patients using pharmacokinetic data from infected patients with the minimum inhibitory concentrations of 6142 P. aeruginosa isolates in U.S. hospitals collected during 2009. The probability of achieving bactericidal activity in this population, referred to as the cumulative fraction of response (CFR), was calculated for each antimicrobial. An optimal regimen was defined as achieving a CFR of ≥90%. The majority of isolates were collected from male inpatients who were not in an intensive care unit (ICU) and were over age 65 years. Standard dosing for all antimicrobials failed to achieve optimal CFRs, regardless of hospital location. While high-dose prolonged infusions improved the CFRs for the β-lactams, optimal exposures were only attained by doripenem (2 g every 8 hours infused over 1 hour; 0.5-2 g every 8 hours infused over 4 hours) and meropenem (2 g every 8 hours infused over 0.5 and 3 hours) for all isolates. Non-ICU isolates had approximately 5-10% higher CFRs compared with those collected in the ICU. Lower-respiratory-tract isolates had a lower predicted CFR than did isolates from the blood and skin or wounds. Simulated pharmacodynamic profiles of i.v. antimicrobials commonly used to treat P. aeruginosa indicated that higher dosages and prolonged infusion times are needed to achieve optimal exposure for bactericidal activity.

Candida bloodstream infections: comparison of species distribution and resistance to echinocandin and azole antifungal agents in Intensive Care Unit (ICU) and non-ICU settings in the SENTRY Antimicrobial Surveillance Program (2008–2009)

Minimum inhibitory concentration (MIC) data from the SENTRY Antimicrobial Surveillance Program generated by reference methods were analysed to compare the antifungal resistance profiles and species distribution of Candida bloodstream infection (BSI) isolates obtained from patients in the Intensive Care Unit (ICU) and those from non-ICU locations. Results from 79 medical centres between 2008 and 2009 were tabulated. MIC values were obtained for anidulafungin, caspofungin, micafungin, fluconazole, posaconazole and voriconazole. Recently revised Clinical and Laboratory Standards Institute breakpoints for resistance were employed. A total of 1752 isolates of Candida spp. were obtained from ICU (779; 44.5%) and non-ICU (973; 55.5%) settings. The frequency of ICU-associated Candida BSI was higher in Latin America (56.5%) compared with Europe (44.4%) and North America (39.6%). The frequency of candidaemia in the ICU decreased both in Latin America and North America over the 2-year study period. Approximately 96% of isolates both in ICU and non-ICU settings were caused by only five species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei). Resistance both to azoles and echinocandins was uncommon in ICU and non-ICU settings. Overall, fluconazole resistance was detected in 5.0% of ICU isolates and 4.4% of non-ICU isolates. Candida glabrata was the only species in which resistance to azoles and echinocandins was noted, and this multidrug-resistant phenotype was found in both settings. In conclusion, the findings from this global survey indicate that invasive candidiasis can no longer be considered to be just an ICU-related infection, and efforts to design preventive and diagnostic strategies must be expanded to include other at-risk populations and hospital environments. Concern regarding C. glabrata must now include resistance to echinocandins as well as azole antifungal agents.

Further Increases in Carbapenem-, Amikacin-, and Fluoroquinolone-Resistant Isolates of Acinetobacter spp. and P. aeruginosa in Korea: KONSAR Study 2009

PurposeThe increasing prevalence of antimicrobial resistant bacteria has become a serious worldwide problem. The aim of this study was to analyze antimicrobial resistance data generated in 2009 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program.Materials and MethodsSusceptibility data were collected from 24 hospitals and two commercial laboratories. In the analysis, resistance did not include intermediate susceptibility. Duplicate isolates were excluded from the analysis of hospital isolates, but not from the commercial laboratory isolates.ResultsAmong the hospital isolates, methicillin-resistant Staphylococcus aureus, penicillin G-non-susceptible Streptococcus pneumoniae based on meningitis breakpoint, and ampicillin-resistant Enterococcus faecium remained highly prevalent. The proportion of vancomycin-resistant E. faecium gradually increased to 29%. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae increased to 17% and 33%, respectively, and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa increased to 33%, 67% and 39%, respectively. Amikacin-resistant Acinetobacter spp. increased to 48%. Imipenem-resistant Acinetobacter spp. and P. aeruginosa increased to 51% and 26%, respectively. Higher resistance rates were observed in intensive care unit (ICU) isolates than in non-ICU isolates among the isolates from hospitals. Resistance rates were higher in hospital isolates than in clinic isolates among the isolates from commercial laboratories.ConclusionAmong the hospital isolates, ceftazidime-resistant K. pneumoniae and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp., and P. aeruginosa further increased. The increase in imipenem resistance was slight in P. aeruginosa, but drastic in Acinetobacter spp. The problematic antimicrobial-organism combinations were much more prevalent among ICU isolates.

Pharmacodynamic Profiling of Antimicrobials against Gram-negative Respiratory Isolates from Canadian Hospitals

With diminishing antimicrobial potency, the choice of effective empirical therapy has become more challenging. Thus, the pharmacodynamic evaluation of potential therapies is essential to identify optimal agents, doses and administration strategies. Monte Carlo simulation was conducted for standard and/or prolonged infusion regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, doripenem, ertapenem, meropenem and piperacillin/tazobactam. Minimum inhibitory concentrations were obtained for Escherichia coli (n=64 respiratory isolates), Enterobacter cloacae (n=53), Klebsiella pneumoniae (n=75) and Pseudomonas aeruginosa (n=273) throughout Canada. The cumulative fraction of response (CFR) was calculated using bactericidal targets for each regimen against each species. A CFR ≥90% was defined as optimal. All cefepime, doripenem, ertapenem and meropenem regimens achieved optimal exposures against Enterobacteriaceae, whereas target attainment was organism and dose dependent for the other agents. Prolonged infusion doripenem and meropenem 1 g and 2 g every 8 h, along with standard infusion doripenem and meropenem 2 g every 8 h, were the only regimens to attain optimal exposures against P aeruginosa. Ciprofloxacin had the lowest CFR against P aeruginosa, followed by cefepime. Among the P aeruginosa isolates collected in the intensive care unit (ICU) compared with the wards, differences of 0.5% to 10% were noted in favour of non-ICU isolates for all agents; however, marked differences (10% to 15%) in CFR were observed for ciprofloxacin in favour of ICU isolates. Standard dosing of cefepime, doripenem, ertapenem and meropenem has a high likelihood of obtaining optimal pharmacodynamic indexes against these Enterobacteriaceae. For P aeruginosa, aggressive treatment with high-dose and/or prolonged infusion regimens are likely required to address the elevated resistance rates of respiratory isolates from Canada.

P666 Comparative in vitro activity of tigecycline against ICU-and non-ICU isolates offive clinically important Gram-negative pathogens: results of the German T.E.S.T.Surveillance Programme 2005

P666 Comparative in vitro activity of tigecycline against ICU-and non-ICU isolates offive clinically important Gram-negative pathogens: results of the German T.E.S.T.Surveillance Programme 2005

Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global, longitudinal antimicrobial resistance surveillance network of greater than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2002, 15 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. During this 4-year period, the antimicrobial activity of 11 broad-spectrum agents was assessed against 5389 bacterial isolates using Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards)-recommended methods with interpretive criteria. Analysis of the MIC results for pathogens isolated from patients hospitalized in intensive care units (ICUs) were compared to results from pathogens isolated in non-ICU settings. Among Enterobacteriaceae (3884 strains), the carbapenems (imipenem and meropenem) demonstrated the highest susceptibility rates (≥98.7%) and with only a 1% increase in resistance for ICU isolates compared to non-ICU organisms. Other antimicrobial agents tested demonstrated consistently higher susceptibility rates against Enterobacteriaceae isolates from ICU (89.7–98.7%) and non-ICU (93.2–99.9%) areas. For the nonfermentative Gram-negative bacilli, the rank order of the most active agents having lowest percentage resistance rates were tobramycin (15.5%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < meropenem (21.9%) for ICU isolates, and meropenem (7.8%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < tobramycin (12.9%) among non-ICU strains. All tested agents showed lower susceptibility rates (range, 1.0–15.3%) and higher resistance rates (range, 0.1–15.1%) for both Enterobacteriaceae and nonfermentative Gram-negative bacilli among the ICU isolates compared to the non-ICU isolates (except for ciprofloxacin against Enterobacteriaceae). Continued surveillance of these broad-spectrum antimicrobial agents in both ICU and general hospital wards appears warranted to monitor the occurrence and spread of antimicrobial resistance in pathogens causing serious infections in these care areas and the possible emergence of resistance mechanisms that could compromise empiric carbapenem therapy.