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.

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% 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% 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% 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% 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.

Actualización de la resistencia a antimicrobianos de bacilos Gram negativos aislados en hospitales de nivel III de Colombia: años 2006, 2007 y 2008 / Antimicrobial resistance of Gram negative bacilli isolated from terciary-care hospitals in Colombia

Introducción. La resistencia a antimicrobianos se ha identificado como uno de los mayores problemas de salud pública, por lo cual debe ser vigilada permanentemente a través de sistemas efectivos de vigilancia. Objetivo. Describir el comportamiento de la resistencia antimicrobiana de bacilos Gram negativos, en las instituciones hospitalarias pertenecientes al Grupo para el Estudio de la Resistencia Nosocomial en Colombia, de enero 2006 a diciembre 2008. Materiales y métodos. Es un estudio descriptivo realizado con la información de los perfiles de sensibilidad bacteriana suministrada por 14 hospitales de tercer nivel en siete ciudades de Colombia, definidos como el Grupo para el Estudio de la Resistencia Nosocomial en Colombia, de enero de 2006 a diciembre de 2008. Usando el software WHONET 5.4, se describe el comportamiento de la resistencia bacteriana de las especies de Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae y Enterobacter cloacae) y bacilos Gram negativos no fermentadores (Pseudomonas aeruginosa y Acinetobacter baumannii) frente a antibióticos seleccionados como marcadores de resistencia en salas generales y unidades de cuidados intensivos de pacientes adultos.Resultados. En algunas Enterobacteriaceae se observó disminución de la frecuencia de resistencia antimicrobiana, mientras que P. aeruginosa se consolida como un germen multirresistente, cuyas frecuencias de resistencia continúan en aumento. Conclusiones. Los programas de vigilancia pueden tener un impacto en la disminución significativa de gérmenes multirresistentes, ya que contribuyen a la adecuada implementación de protocolos encaminados a fortalecer las estrategias de control de infecciones y el manejo racional de antibióticos en cada hospital.

Introduction. Antimicrobial resistance has been identified as one of the major public health problems worldwide. To facilitate its control, bacterial resistance levels must be monitored permanently by effective surveillance systems.Objective. To describe the antimicrobial resistance patterns of Gram negative bacilli in Colombian hospitals over a 3-year period. Materials and methods. This descriptive study used the bacterial susceptibility profiles provided by 14 tertiary-care hospitals belonging to the Colombian Nosocomial Resistance Study Group. The hospitals were located in 7 major cities in Colombia, and provided records over the period January 2006 to December 2008. Using WHONET 5.4, the antimicrobial resistance patterns were described for the Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) and non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii). Comparisons were made in the bacterial responses to selected antibiotics in samples from general wards and from adult intensive care units. Results. The antimicrobial resistance frequencies of several Enterobacteriaceae species showed a decreasing trend. In contrast, P. aeruginosa was demonstrated to be a multidrug-resistance organism with increasing resistance frequencies.Conclusions. These data emphasize the importance of surveillance programs in detecting presence of multidrug-resistant organisms. This information will aid the implementation of protocols aimed to strengthen the infection control strategies and antibiotic stewardship in each hospital.

Treatment options for multidrug-resistant nonfermenters.

Multidrug-resistant nonfermenters are a worldwide threat. Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with high mortality and treatment failures. In addition, therapeutic options are increasingly narrowed, mainly due to widespread resistance in these pathogens and a shortage of new antimicrobial compounds. Hence, old, potent but toxic antibiotics such as the polymyxins are re-emerging as therapeutic options. Maximizing pharmacokinetics/pharmacodynamics with existing agents is also a worthwhile approach to explore. This problem exemplifies the critical need for new drug development for multidrug-resistant Gram-negative microorganisms.

[Antimicrobial resistance of Gram negative bacilli isolated from tertiary-care hospitals in Colombia]. / Actualización de la resistencia a antimicrobianos de bacilos Gram negativos aislados en hospitales de nivel III de Colombia: años 2006, 2007 y 2008.

INTRODUCTION: Antimicrobial resistance has been identified as one of the major public health problems worldwide. To facilitate its control, bacterial resistance levels must be monitored permanently by effective surveillance systems. OBJECTIVE: To describe the antimicrobial resistance patterns of Gram negative bacilli in Colombian hospitals over a 3-year period. MATERIALS AND METHODS: This descriptive study used the bacterial susceptibility profiles provided by 14 tertiary-care hospitals belonging to the Colombian Nosocomial Resistance Study Group. The hospitals were located in 7 major cities in Colombia, and provided records over the period January 2006 to December 2008. Using WHONET 5.4, the antimicrobial resistance patterns were described for the Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) and non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii). Comparisons were made in the bacterial responses to selected antibiotics in samples from general wards and from adult intensive care units. RESULTS: The antimicrobial resistance frequencies of several Enterobacteriaceae species showed a decreasing trend. In contrast, P. aeruginosa was demonstrated to be a multidrug-resistance organism with increasing resistance frequencies. CONCLUSIONS: These data emphasize the importance of surveillance programs in detecting presence of multidrug-resistant organisms. This information will aid the implementation of protocols aimed to strengthen the infection control strategies and antibiotic stewardship in each hospital.