Clinical and economic impact of generic versus brand name meropenem use in an intensive care unit in Colombia

Abstract Background: Recent studies suggest that sustained use of generic antibiotics may be associated with clinical failure and emergence of antibacterial resistance. The present study was designed to determine the clinical outcome between the use of generic meropenem (GM) and brand-name meropenem (BNM). Additionally, this study evaluated the economic impact of GM and BNM to determine if the former represents a cost-effective alternative to the latter. Methods: Patients treated between January 2011 and May 2014 received GM while patients treated between June 2014 and March 2017 received BNM. Mortality was compared between groups. Total infection cost was defined by the cost of antimicrobial consumption, length of stay, and laboratory and imaging exams until infection resolution. Findings: A total of 168 patients were included; survival rate for the 68 patients treated with GM was 38% compared to 59% in the patients treated with BNM. Multivariate analysis showed that the variables most strongly-associated with mortality were cardiovascular disease (OR 18.18, 95% CI 1.25-262.3, p = 0.033) and treatment with generic meropenem (OR 18.45, 95% CI 1.45-232.32, p = 0.024). On the other hand, total infection cost did not show a significant difference between groups (BNM $10,771 vs. GM $11,343; p = 0.91). Interpretation: The present study suggests that patients treated with GM have a risk of death 18 times higher compared to those treated with BNM. Furthermore, economic analysis shows that GM is not more cost effective than BNM. Summary: More studies measuring clinical outcomes are needed to confirm the clinical equivalence of brand-name versus generic antibiotics, not only for meropenem but also for other molecules.

Impacto clínico del desescalamiento a ertapenem en pacientes críticos con infecciones por Enterobacteriaceae / Clinical impact of ertapenem de-escalation in critically-ill patients with Enterobacteriaceae infections

Resumen Introducción: Ertapenem ha demostrado eficacia frente a Enterobacteriaceae productoras de β-lactamasas de espectro extendido, pero carece de actividad contra bacterias no fermentadoras; el desescalamiento a este antimicrobiano cuando no existe la presencia de P. aeruginosa podría reducir la presión selectiva contra esta bacteria y mejorar los resultados clínicos. Objetivo: Evaluar el impacto clínico del desescalamiento de antimicrobianos con cobertura anti-pseudomonas a ertapenem, un agente sin este espectro, en pacientes críticos con infecciones por Enterobacteriaceae. Métodos: Se realizó un estudio de cohorte prospectivo en adultos admitidos a Unidades de Cuidado Intensivo (UCI) con infecciones por Enterobacteriaceae, que habían sido desescalados de una cobertura anti-pseudomonas, a un antimicrobiano sin la misma (ertapenem). Se realizó un modelo de riesgo proporcional de Cox comparando mortalidad por cualquier causa y duración de estancia hospitalaria entre aquellos pacientes que permanecieron con cobertura anti-pseudomonas versus aquellos que fueron desescalados a ertapenem. Resultados: 105 pacientes en el grupo anti-pseudomonas fueron comparados con 148 pacientes del grupo de desescalamiento a ertapenem. El desescalamiento estuvo asociado con una menor mortalidad por cualquier causa comparado con los pacientes que permanecieron con cobertura anti-pseudomonas (hazard ratio ajustado 0,24; IC 95%: 0,12-0,46). La estancia hospitalaria en UCI fue similar en ambos grupos. Discusión: Los pacientes de UCI con infecciones por Enterobacteriaceae desescalados a terapia con ertapenem, tuvieron mejores resultados clínicos comparados con aquellos que permanecieron en terapia anti-pseudomonas, sugiriendo que el desescalamiento es una práctica segura en esta población.

Background: Ertapenem has proven to be effective for extended-spectrum beta-lactamases-producing Enterobacteriaceae but lacks activity against non-fermenters; de-escalation to this antibiotic may reduce the selection of resistance to Pseudomonas aeruginosa and improve clinical outcomes. Aim: To evaluate the clinical impact of de-escalation from broad-spectrum anti-pseudomonal agents to ertapenem, a non-pseudomonal antibiotics for Enterobacteriaceae infections in critically-ill patients. Methods: We conducted a prospective cohort study in adult patients admitted to intensive care units (ICUs) who had Enterobacteriaceae infections and were de-escalated from empiric anti-pseudomonal coverage to non-pseudomonal antibiotics. Cox proportional hazards models were performed comparing all-cause mortality and length of hospital stay between patients who remained on anti-pseudomonal coverage versus those who were de-escalated to ertapenem. Results: 105 patients in the anti-pseudomonal group were compared to 148 patients in the ertapenem de-escalation group. De-escalation was associated with lower all-cause mortality compared to patients who remained on anti-pseudomonal coverage (adjusted Hazard Ratio 0.24; 95% CI: 0.12-0.46). The length of ICU stay was similar between the groups. Discussion: ICU patients with Enterobacteriaceae infections de-escalated to ertapenem therapy had better outcomes compared to patients who remained on broad-spectrum, anti-pseudomonal therapy, suggesting that de-escalation is a safe approach amongst ICU patients.

Características clínicas y microbiológicas de la infección intra-abdominal complicada en Colombia: un estudio multicéntrico / Clinical and microbiological characteristics of complicated intra-abdominal infection in Colombia: a multicenter study

Introducción: La infección intra-abdominal complicada adquirida en la comunidad (IIAc-AC) es una causa frecuente de abdomen agudo. Objetivo: Identificar el perfil clínico y microbiológico de la IIAc-AC en cuatro hospitales de Colombia. Métodos: Estudio descriptivo, prospectivo entre 07-2012 y 09-2014 en pacientes de 15 o más años con IIAc-AC. Se midieron las frecuencias de variables socio-demográficas, clínicas, diagnóstico, aislamientos y susceptibilidad antimicrobiana del primer cultivo obtenido asépticamente del sitio de infección. Resultados: 192 pacientes incluidos, 62% hombres, edad media 47,3 años; 38,4% con co-morbilidad, 13% hospitalizados en el último año y 9,4% recibieron antimicrobianos en los últimos seis meses. Fueron admitidos 44,3%, por apendicitis 17,7% por peritonitis y 16,7% por perforación intestinal. El 64,1% de las IIAc-AC fue moderada y tratada con ampicilina/sulbactam (SAM) y ertapenem. En 70,8% se aisló al menos un microorganismo en: 65,1% bacilos gramnegativos (80,0% Escherichia coli, 44,8% susceptible a piperacilina/tazobactam, 65,7% a SAM y 11,2% Klebsiella pneumoniae, 85% susceptibles a SAM) y en 16,7% especies grampositivas (28,1% Streptococcus grupo viridans). La mediana de hospitalización fue siete días y 15,1% fallecieron. Conclusión: Escherichia coli y K. pneumoniae en IIAc-AC son los principales microorganismos a cubrir en la terapia empírica y es necesario conocer la susceptibilidad antimicrobiana en cada región para seleccionar un tratamiento empírico adecuado.

Introduction: Complicated community-acquired intra-abdominal infections (CA-cIAI) are a common cause of acute abdomen. Objective: To identify the clinical and microbiology profile of CA-cIAI in four Colombian hospitals. Methods: This is a prospective, descriptive study, between 08-2012 and 09-2014, including patients with CA-cIAI > 15 years. Data collected included: socio-demographic, clinical, diagnosis, and isolates of the first culture obtained aseptically during surgery with antimicrobial susceptibility. Results: 192 patients were included, 62% men, median age 47.3 years. Co-morbidities were present in 38.4%, 13% had been hospitalized in the previous year 13%, and 9.4% had received antibiotics in the last 6 months; 44.3% were admitted for appendicitis, 17.7% for peritonitis and 16.7% for bowel perforation. CA-cIAI were assessed as moderate in 64.1% of the cases and were treated with ampicillin/sulbactam (SAM) and ertapenem. In 70.8% of cases a bacteria was isolated: 65.1% were gramnegative rods (80.0% Escherichia coli, 44.8% of them susceptible to pipercillin/tazobactam, 65.7% to SAM; 11.2 % were K.pneumoniae, 85% was susceptible for SAM; 16.7% were grampositive cocci (28.1% Streptococci viridans group). The median hospital stay was 7 days and 15.1% died. Conclusions: E. coli, K. pneumoniae and S. viridans were the main organisms to consider in an empiric therapy for CA-cIAI and it is important to know the local epidemiology in order to choose the right antibiotic.