ABSTRACT
OBJECTIVES: This study was designed to simulate standard and optimized dosing regimens for intravenous antibiotics against contemporary populations of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa using MIC distribution data to determine which of the tested carbapenem regimens provided the greatest opportunity for obtaining maximal pharmacodynamic (PD) activity. METHODS: The isolates studied were obtained from the COMPACT-COLOMBIA surveillance program conducted between February and November 2009. Antimicrobial susceptibility testing was conducted by broth microdilution method according to the CLSI guidelines. Doripenem, imipenem-cilastatin, and meropenem, were the modeled antibiotics. A 5,000 patient Monte Carlo simulation was performed for each regimen and PD targets were defined as free drug concentrations above the MIC for at least 40 percent of the dosing interval. RESULTS: All carbapenem regimens obtained optimal exposures against E. coli, unlike the other Enterobacteriaceae tested. Against P. aeruginosa, only a prolonged infusion of doripenem exceeded the 90 percent cumulative fraction of response (CFR) threshold. Worrisomely, no regimens for any of the drugs tested obtained optimal CFR against A. baumannii. For P. aeruginosa intensive care unit (ICU) isolates, CFR was approximately 20 percent lower for isolates collected in the respiratory tract compared with bloodstream or intra-abdominal for imipenem and meropenem. Noteworthy, all doripenem and meropenem regimens achieved greater than 90 percent CFR against bloodstream and respiratory isolates of K. pneumoniae. CONCLUSIONS: Our data suggests that higher dosing and prolonged infusion of doripenem or meropenem may be suitable for empirically treating ICU P. aeruginosa, while none of the carbapenems achieved optimal cumulative fraction of response against A. baumannii. Standard dosing regimens of all the carbapenems tested achieved optimal CFR against E. coli isolates, but higher carbapenem dosages might be required for empiric treatment of K. pneumoniae, particularly from an intra-abdominal source. Non-standard dosage regimens studied in this modeling should be proven effective in prospective clinical trials.
Subject(s)
Humans , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Imipenem/pharmacology , Thienamycins/pharmacology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacokinetics , Colombia , Carbapenems/pharmacokinetics , Escherichia coli/drug effects , Gram-Negative Bacteria/metabolism , Gram-Negative Bacterial Infections/metabolism , Gram-Negative Bacterial Infections/microbiology , Infusions, Intravenous , Intensive Care Units , Imipenem/pharmacokinetics , Klebsiella pneumoniae/drug effects , Monte Carlo Method , Microbial Sensitivity Tests/methods , Pseudomonas aeruginosa/drug effects , Thienamycins/pharmacokineticsABSTRACT
Las infecciones asociadas a la atención en salud son uno de los eventos secundarios más comunes entre los pacientes hospitalizados. Estas infecciones se relacionan con incrementos en la morbilidad, la mortalidad, la estancia hospitalaria y los costos asociados a la atención en salud. La clorhexidina ha probado ser útil en la prevención de infecciones asociadas a la atención en salud, debido a su amplio espectro antiséptico, su eficacia y su margen de seguridad. Diferentes estudios han demostrado efectividad de la clorhexidina en la prevención de infecciones tales como las del sitio operatorio, la bacteriemia asociada al catéter vascular, la neumonía asociada al respirador, las infecciones maternas y neonatales, y otras infecciones causadas por Staphylococcus aureus. La mayoría de los estudios han encontrando superioridad de este compuesto sobre otros antisépticos, en la prevención y control de infecciones asociadas a la salud.
Health care related infections are one of the most common adverse events among hospitalized patients. These types of infections are related to an increased morbidity, mortality, hospitalization time, and health care related costs. Chlorhexidine has been proven to be useful for preventing health care related infections due to its wide antiseptic spectrum, effectiveness and safety. Different studies have shown evidence about the effectiveness of chlorhexidine in the prevention of infections related to surgical sites, vascular catheter related bloodstream infections, ventilator associated pneumonia, maternal and neonatal infections and other infections caused by Staphylococcus aureus. Most studies have found superiority of this compound against other antiseptics in the prevention and control of health care related infections.