RESUMEN
BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is examining aerobic and facultatively anaerobic gram-negative bacilli (GNB) isolated from intra-abdominal infections. This report summarizes the 2005 annual data. METHODS: During 2005, 76 medical centers in 31 countries in five regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 5,476 unique aerobic and facultatively anaerobic GNB were isolated. Enterobacteriaceae accounted for 86% (4,711) of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most reliably active against the Enterobacteriaceae, whereas ampicillin/sulbactam most often was the least active. Escherichia coli was the species most commonly isolated, at 48% (2,654). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 12% (325/2,329) of E. coli and 18% (151/856) of Klebsiella spp. In general, ESBL producers demonstrated lower susceptibility to the majority of the antibiotics than the non-producers; however, ESBL producers usually were susceptible to the carbapenems tested. CONCLUSIONS: In 2005, antibiotic resistance continued to be a problem among GNB isolated from intra-abdominal infections, with the highest resistance rates observed in the Asia/Pacific region. Imipenem-cilastatin, ertapenem, and amikacin were the agents most consistently active in vitro against the Enterobacteriaceae isolated.
Asunto(s)
Cavidad Abdominal/microbiología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Bacterias Aerobias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Bacilos Gramnegativos Anaerobios Facultativos/efectos de los fármacos , Enterobacteriaceae/efectos de los fármacos , Salud Global , Infecciones por Bacterias Gramnegativas/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Vigilancia de la Población , Resistencia betalactámicaRESUMEN
BACKGROUND: Increasing nosocomial pathogen resistance to available antimicrobial agents is of growing concern. While higher MICs can diminish antimicrobial effectiveness, dose adjustments often mitigate this effect. This study's objective was to ascertain whether MICs among major pathogens in the ICU to several commonly used agents have increased enough to significantly impact their ability to achieve bactericidal effect. METHODS: Cefepime, ceftriaxone, imipenem and piperacillin-tazobactam MICs were determined with 74,394 Gram-negative bacilli obtained from ICU patients with various infections in the US between 1993 and 2004. Results were grouped into four 3-year periods. The predicted cumulative fraction of response (CFR) was estimated based on patient-derived pharmacokinetic values and Monte Carlo simulation. Trends in CFR over the four study periods were assessed using the Cochran-Armitage test. The primary analysis included all organisms combined; Pseudomonas aeruginosa and Acinetobacter species were also evaluated individually. RESULTS: In the primary analysis, imipenem 500 mg q6h showed CFRs from 87% to 90% across all four study periods, with a trend toward slightly improved bactericidal target attainment (p < 0.01). CFRs for cefepime 2 g q12h and piperacillin-tazobactam 4.5 g q6h both declined by 2% (p < 0.01 and p < 0.05, respectively), reflecting upward shifts in the underlying MIC distributions. Ceftriaxone had <52% CFR for all regimens in all periods, with no significant trend. Against P. aeruginosa, significant declines in CFR were seen for (range, p-value): imipenem 1 g q8h (82%-79%, p < 0.01), cefepime 1 g q12h (70%-67%, p < 0.01), cefepime 2 g q12h (84%-82%, p < 0.05), piperacillin-tazobactam 3.375 g q6h (76%-73%, p < 0.01), piperacillin-tazobactam 4.5 g q8h (71%-68%, p < 0.01), and piperacillin-tazobactam 4.5 g q6h (80%-77%, p < .01). Against Acinetobacter spp., all regimens of imipenem, cefepime and piperacillin-tazobactam showed significant declines in CFR over time (p < 0.01). CONCLUSION: Our observations suggest that as a result of increasing antimicrobial resistance among ICU pathogens in the US, drug effectiveness, assessed as a function of individual agents' ability to attain pharmacodynamic targets, has declined, especially with P. aeruginosa and Acinetobacter spp. Cefepime 2 g q8h and imipenem were the most potent agents against these species, respectively. More aggressive dosing of all of the agents characterized could preserve their clinical utility, but this must be balanced with safety and tolerability issues by the physician.
Asunto(s)
Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , beta-Lactamas/farmacología , Antibacterianos/farmacocinética , Humanos , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Método de Montecarlo , Estados UnidosRESUMEN
During the 12-year period from 1993 to 2004, antimicrobial susceptibility profiles of 74,394 gram-negative bacillus isolates recovered from intensive care unit (ICU) patients in United States hospitals were determined by participating hospitals and collected in a central location. MICs for 12 different agents were determined using a standardized broth microdilution method. The 11 organisms most frequently isolated were Pseudomonas aeruginosa (22.2%), Escherichia coli (18.8%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (9.1%), Acinetobacter spp. (6.2%), Serratia marcescens (5.5%), Enterobacter aerogenes (4.4%), Stenotrophomonas maltophilia (4.3%), Proteus mirabilis (4.0%), Klebsiella oxytoca (2.7%), and Citrobacter freundii (2.0%). Specimen sources included the lower respiratory tract (52.1%), urine (17.3%), and blood (14.2%). Rates of resistance to many of the antibiotics tested remained stable during the 12-year study period. Carbapenems were the most active drugs tested against most of the bacterial species. E. coli and P. mirabilis remained susceptible to most of the drugs tested. Mean rates of resistance to 9 of the 12 drugs tested increased with Acinetobacter spp. Rates of resistance to ciprofloxacin increased over the study period for most species. Ceftazidime was the only agent to which a number of species (Acinetobacter spp., C. freundii, E. aerogenes, K. pneumoniae, P. aeruginosa, and S. marcescens) became more susceptible. The prevalence of multidrug resistance, defined as resistance to at least one extended-spectrum cephalosporin, one aminoglycoside, and ciprofloxacin, increased substantially among ICU isolates of Acinetobacter spp., P. aeruginosa, K. pneumoniae, and E. cloacae.