Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

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.

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

ABSTRACT A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction.

Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae

Abstract Background: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. Methods: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. Results: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p = 0.044). The addition of carbapenem was not associated with increased survival. Conclusion: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.

Fatores de risco e letalidade de infecção da corrente sanguínea laboratorialmente confirmada, causada por patógenos não contaminantes da pele em recém-nascidos / Risk factors and lethality of laboratory-confirmed bloodstream infection caused by non-skin contaminant pathogens in neonates

OBJECTIVE: To evaluate risk factors and lethality of late onset laboratory-confirmed bloodstream infection (ICSLC) in a Brazilian neonatal unit for progressive care (NUPC). Methods: This was a case-control study, performed from 2008 to 2012. Cases were defined as all newborns with late onset ICSLC, excluding patients with isolated common skin contaminants. Controls were newborns who showed no evidence of late onset ICSLC, matched by weight and time of permanence in the NUPC. Variables were obtained in the Hospital Infection Control Committee (HICC) database. Analysis was performed using the Statistical Package for the Social Sciences (SPSS). The chi-squared test was used, and statistical significance was defined as p < 0.05, followed by multivariate analysis. RESULTS: 50 patients with late onset ICSLC were matched with 100 patients without late onset ICSLC. In the group of patients with late onset ICSLC, a a significant higher proportion of patients who underwent surgical procedures (p = 0.001) and who used central venous catheter (CVC) (p = 0.012) and mechanical ventilation (p = 0.001) was identified. In multivariate analysis, previous surgery and the use of CVC remained significantly associated with infection (p = 0.006 and p = 0.047; OR: 4.47 and 8.99, respectively). Enterobacteriacea was identified in 14 cases, with three (21.4%) deaths, and Staphylococcus aureus was identified in 20 cases, with three (15%) deaths. CONCLUSIONS: Surgical procedures and CVC usage were significant risk factors for ICSLC. Therefore, prevention practices for safe surgery and CVC insertion and manipulation are essential to reduce these infections, in addition to training and continuing education to surgical and assistance teams.

OBJETIVO: Avaliar os fatores de risco e a letalidade da infecção da corrente sanguínea laboratorialmente confirmada (ICSLC) de início tardio em uma Unidade Neonatal de Cuidados Progressivos (UNCP) brasileira. MÉTODOS: Trata-se de um estudo caso-controle realizado de 2008 a 2012. Os casos foram definidos como todos os recém-nascidos com ICSLC de início tardio, excluindo pacientes isolados com contaminantes da pele comuns. Os controles foram recém-nascidos que não mostraram qualquer evidência de ICSLC de início tardio, sendo separados por peso e tempo de permanência na UNCP. As variáveis foram obtidas na base de dados da Comissão de Controle de Infecção Hospitalar (CCIH). A análise foi realizada utilizando o Pacote Estatístico para Ciências Sociais. O teste χ² foi utilizado e a relevância estatística foi definida como p < 0,05, seguida pela análise multivariada. RESULTADOS: No estudo, 50 pacientes com ICSLC de início tardio foram combinados com 100 pacientes sem ICSLC de início tardio. No grupo de pacientes com ICSLC de início tardio, identificamos uma proporção significativamente maior de pacientes que foram submetidos a procedimentos cirúrgicos (p = 0,001) e que usaram cateter venoso central (CVC) (p = 0,012) e ventilação mecânica (p = 0,001). Na análise multivariada, cirurgia prévia e uso de CVC permaneceram significativamente associados à infecção (p = 0,006 e p = 0,047; OU: 4,47 e 8,99, respectivamente). A Enterobacteriacea foi identificada em 14 casos, com três (21,4%) óbitos, e Staphylococcus aureus foi identificado em 20 casos, com três (15%) óbitos. CONCLUSÕES: Procedimentos cirúrgicos e uso de CVC constituíram fatores de risco significativos para ICSLC. Portanto, práticas de prevenção para cirurgia segura, inserção e manipulação de CVC são essenciais para reduzir essas infecções, além de treinamento e educação contínua às equipes cirúrgicas e de assistência.

Mortalidad por bacteriemia causada por Escherichia coli y Klebsiella spp. productoras de beta lactamasas de espectro extendido: cohorte retrospectiva en un hospital de Lima, Perú / Mortality caused by bacteremia Escherichia coli and Klebsiella spp. extended-spectrum beta-lactamase- producers: a retrospective cohort from a hospital in Lima, Peru

Objetivos. Evaluar los factores asociados a la mortalidad causada por bacteriemias por Escherichia coli y Klebsiella spp. productoras de beta lactamasas de espectro extendido (BLEE). Materiales y Métodos. Se realizó un estudio de cohortes retrospectivo, que incluyó 85 pacientes mayores de 16 años con diagnóstico de bacteriemia por Escherichia coli o Klebsiella spp. hospitalizados entre 2006 y 2008 en el Hospital Nacional Cayetano Heredia. Las cohortes se clasificaron de acuerdo a la producción de BLEE según los resultados de los hemocultivos. Se evaluaron los factores asociados a la mortalidad cruda y atribuible empleando regresión de Poisson en un modelo multivariado, con lo que se obtuvo riesgos relativos ajustados (RRa). Además, se construyeron curvas de mortalidad. Resultados. Se encontró que el 35,3% de las bacteriemias fueron debidas a cepas productoras de BLEE. El análisis de la mortalidad cruda mostró una mayor mortalidad en el grupo de cepas productoras de BLEE (63,3%). El RRa fue de 1,5 (IC95%: 1,02-2,3). En el caso de mortalidad atribuible, la proporción también fue mayor (63,3%), el RRa fue de 1,9 (IC95%: 1,2-2,9). El uso de catéter venoso central fue otro factor asociado tanto a la mortalidad cruda (RRa= 2,4; IC95%: 1,2- 4,8) como a la mortalidad atribuible (RRa= 3,8; IC95%: 1,6-8,8). Conclusiones. La producción de BLEE es un factor de riesgo independiente para mortalidad por bacteriemia causada por E. coli y Klebsiella spp. Su presencia debe evaluarse tras la sospecha diagnóstica y la elaboración de la terapéutica inicial, lo que podría disminuir la mortalidad por esta causa.

Objectives. To evaluate the factors associated to mortality caused by bacteremia due to Escherichia coli and Klebsiella spp. producers of extended-spectrum beta-lactamase (ESBL). Materials and methods. We performed a retrospective cohort study, including 85 patients older than 16 and diagnosed with bacteremia by Escherichia coli or Klebsiella spp., hospitalized between 2006 and 2008 in Cayetano Heredia National Hospital. Cohorts were classified according to the ESBL production following blood culture results. Factors associated to gross and attributable mortality were evaluated using the Poisson regression in a multivariate model, through which adjusted relative risks (ARRs) were obtained. Mortality curves were also built. Results. 35.3% of bacteremia cases were caused by ESBL-producing strains. The analysis of gross mortality showed a higher mortality rate in the group with ESBL producing strains (63.3%), ARR being 1.5 (CI 95%: 1.02-2.3). In the case of the attributable mortality, the proportion was also higher (63.3%), ARR being 1.9 (CI 95%: 1.2-2.9). The use of a central venous catheter was another factor associated to both gross mortality (ARR= 2.4; CI 95%: 1.2-4.8) and attributable mortality (ARR= 3.8; CI 95%: 1.6-8.8). Conclusions. The production of ESBL is an independent risk factor for bacteremia mortality caused by E. coli and Klebsiella spp. Its presence should be evaluated following diagnosis consideration and initial therapy elaboration, which could in turn decrease the mortality by this cause.