Assessing the pharmacodynamic profile of intravenous antibiotics against prevalent Gram-negative organisms collected in Colombia

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.

Acinetobacter baumannii: No more a choosy intruder.

Context: Acinetobacter baumannii, a non-fermenter, is fast coming up the list of pathogens causing nosocomial infections. Earlier considered to be a harmless colonizer, or at the most, a pathogen causing mostly respiratory tract infections, it has slowly but successfully emerged as a ubiquitous pathogen causing both community as well as health care associated infections. It has acquired multidrug resistance, and seems to be no more selective in mainly attacking any one or two body systems. According to recent reports, a shy selective bacterium has turned into a dangerous pathogen, capable of causing infections anywhere in the body, thereby adding extra furrows on the forehead of medical community worldwide. AIMS: To determine the range of infections caused by A. baumannii, and the frequencies thereof, in our tertiary care hospital; and to study their resistance patterns. Materials and Methods: A total of 88 isolates of A. baumannii were found from a variety of clinical samples, from hospitalized patients as well as patients attending the outpatient departments. The isolates were subjected to disc-diffusion method for antibiotic sensitivity testing. Results: Acinetobacter was mostly recovered from samples of pus, followed by endotracheal tube, urine, sputum samples, etc., Imipenem showed highest sensitivity, while other drugs with good sensitivity patterns were aminoglycosides and piperacillin-tazobactum. Conclusions: In this tertiary care institution of ours, A. baumannii isolates have shown a high frequency of drug resistance, with imipenem being the best sensitive drug. This non-fermenter is the cause of a variety of infections, irrespective of whether the individuals are hospitalized or are outdoor patients.

Aspectos farmacológicos de meropenem / Pharmacological topics of meropenem

Meropenem is more stable than imipenem to renal dehydropeptidase I and can be used as a monodrug. It is bactericidal against most grampositive and gramnegative, aerobic and anaerobic species. Compared to imipenem, meropenem is more active against pseudomonas aeuginosa, burkholderia cepacia and some multiresistant nosocomial gramnegative strains because it is less inductor of extended spectrum B lactamases but may favor resistance against other antibiotic groups by an efflux pump induction. Its systemicdistribution in the extracellular space includes the central nervous system and is most excreted by glomerular filtration. As meropenem is more soluble than imipenem, it can be administered in bolus. Security profile: it rarely causes seizures, a frecuent effect observed with imipenem during tratment of bacterial meningitis in children. Other adverse reactions (local pain, pruritus and diarrhea) are as frecuent as described with imipenem

Identificación de especies de enterococcus en muestras clínicas y susceptibilidad a agentes antimicrobianos / Identification of enterococcus species from clinical samples and susceptibility to antimicrobial agents

The genus enterococcus has 12 species of which, E faecalis and E faecium are most important in human infections. A progressive resistance to penicillin and ampicillin has been detected in these species. The aim of this work was to identify Enterococcus species isolated in a hospital and to study their antimicrobial susceptibility. We studied 209 Enterococcus species coming from patients admitted to a public hospital. Their susceptibility to penicillin, ampicillin, imipenem, vancomycin, tetracycline, chloramphenicol, ciprofloxacin, gentamycin and streptomycin was determined with the agar dilution technique. Eighty seven percent of species were E faecalis and 7,1 percent were E fecium, other isolated species were E hirae, E casseliflaws, E avium, E solitarius and E faecalis variant. 38 percent of these species were isolated from the urinary tract, 22 percent from the skin and 14 percent from surgical wounds. All E faecalis species were susceptible to penicillin, ampicillin, imipenem and vancomycin; 27,3 percent were susceptible to tetracycline, 54,7 percent to chloramphenicol and 80 percent to ciprofloxacin. Seventy three percent of E faecium species were susceptible to penicillin, 80 percent to ampicillin and 60 percent to imipenem. 62 percent of E faecalis and 42.4 percent of E faecium were resistant to streptomycin. It is concluded that the correct identification of Enterococcus species has therapeutic implications

Uso de imipenem-cilastatin / Imipenem-cilastatin use

El Imipenem-Cilastatín es un nuevo antibiótico ß-lactámico que pertenece a la familia de los carbapenem. Se trata de una combinación fija (1:1) de un derivado de la tienamicina (imipenenm) con un inhibidor de una dipeptidasa renal; la dehidropeptidasa I (Cilastatín), la combinación del abtibiótico con esta última sustancia, impide su hidrólisis e inactivación renal. Este antimicrobiano tiene la actividad antibacterial más amplia de todos los antibióticos disponibles para uso en humanos. Es activo contra estreptococos (incluyendo enterecocos), estafilococos y los aerobios gram-negativos, incluso P.aeruginosa. Las principales reacciones adversas han sido náuseas y vómitos los cuales ocurren durante la infusión intravenosa; además de convulsiones. La dosis pediátrica varía de 60 a 100 mg/kg/día cada 6 horas. El imipenem no debe ser utilizado rutinariamente. Su uso está justificado en infecciones producidas por gérmenes multiresistentes, no susceptibles a otros ß-lactámicos.

Actividad comparativa in vitro de imipenem y otros 20 antimicrobianos contra 1434 cepas bacterianas aisladas en el medio hospitalario / In vitro comparative activity of imipenem and other 20 antimicrobials against 1434 bacterial nosocomial isolated strains

Se estudió la actividad in vitro de imipenem y otros 20 antimicrobianos contra 1434 cepas de cultivos provenientes de pacientes atendidos en el hospital durante un periodo de ocho meses. Se determinaron laws concentraciones inhibidoras mínimas (CIM) por la técnica de dilución en agar. Se informan los porcentajes de resistencia antimicrobiana de enterobacterias Pseudomonas aeruginosa, Acinetobacter y estaqfilococos. Los patrones de resistencia de las enterobacterias (975 cepas) a amikacina, netilmicina, cefalosporinas de tercera generación y piperacilina fueron bajos (<20 por ciento), en comparación con el resto de los antimicrobianos estudios. Comparativamente el promedio de resistencia de las enterobacterias a imipenem fue de 1.4 por ciento, con significncia estaqdística (p<0.05) en relación con el resto de los antimicrobianos. El promedio de resistencia de Pseudomonas aeruguinosa (251 cepas) a imipenem fue de 6.4 por ciento, con significancia estadística (p<0.05) con el resto de los antimicrobianos. Resultados similares se informan con Acinetobacter. En cuanto a los estafilococos, todas las cepas de S. aureus fueron sensibles a imipenem, y 3.5 por ciento de cepas de estafilococo coagulasa negativo fueron resistentes al mismo. Se concluye por el comportamaiento in vitro de las cepas bacterianas estudiadas, que imipenem es una excelente alternativa para el manejo de infecciones causadas por bacilos gramnegativos multirresistentes y estafilococos.