Early use of polymyxin B reduces the mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection

ABSTRACT Polymyxin B is one of the last resort option for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection in China. Therefore, the timing of administration of polymyxin is frequently delayed. We collected 40 cases of CRKP bloodstream infections (BSIs) treated with combinations based on polymyxin B over 30 months. The primary outcome, 30-day mortality rate, was 52.5% (21/40). Early administration of polymyxin B is meant to administer the drug within 48 h of diagnosing bacteremia. Delayed administration was considered when polymyxin B was administered after 48 h of bacteremia onset. Polymyxin B duration and total dosages were similar in the two groups (11.57 days versus 11.76 days, p = 0.919; 1306.52 mg versus 1247.06 mg, p = 0.711). Compared with delayed administration, early use of polymyxin B-based combination therapy had a significant increase in the rate of bacterial clearance (65.22% versus 29.41%, p = 0.025; OR = 0.533) and decreased 30-day mortality (39.13% versus 70.59%, p = 0.045; OR = 0.461) and overall mortality (43.48% versus 82.35%, p = 0.022; OR = 0.321).

Factores predictores de mortalidad intrahospitalaria en pacientes adultos con infecciones por Klebsiella pneumoniae resistente a carbapenémicos y colistín: un estudio de cohorte retrospectivo / Risk factors for in-hospital mortality among adult patients infected with colistin-resistant carbapenemase producing Klebsiella pneumoniae: a retrospective cohort study

Resumen Introducción: La emergencia de Klebsiella productora de carbapenemasas resistente a colistín representa un desafío clínico y un problema emergente. Objetivo: Evaluar la mortalidad intrahospitalaria y sus potenciales factores de riesgo en pacientes internados con infecciones clínicas por Klebsiella pneumoniae productora de carbapenemasas (KPC) resistente a colistín. Material y Método: Realizamos un estudio de cohorte retrospectivo, incluyendo pacientes adultos admitidos a un hospital universitario de tercer nivel en Buenos Aires, infectados por KPC resistente a colistín. El evento primario considerado fue la mortalidad intrahospitalaria. Se utilizaron modelos generalizados lineales para evaluar potenciales predictores de dicho evento. Resultados: En total, se identificaron 18 pacientes hospitalizados que presentaron una infección clínica por esta bacteria durante el año 2016 y que fueron incluidos en el análisis final. La mortalidad intrahospitalaria en esta cohorte fue de 38,9%. La presencia de bacteriemia, la injuria renal aguda al momento del diagnóstico y la presencia de shock séptico se asociaron a la ocurrencia del evento primario. Conclusión: El desarrollo de infecciones clínicamente relevantes por KPC resistente a colistín en pacientes internados es frecuente y presenta una elevada mortalidad. En nuestra cohorte, la presencia de shock e injuria renal aguda al momento del diagnóstico se asociaron a un incrementado riesgo de mortalidad intrahospitalaria. Futuras investigaciones deberían corroborar estos hallazgos e investigar factores adicionales que permitan identificar tempranamente a aquellos pacientes que presentarán eventos desfavorables.

ABSTRACT Background: The emergence of colistin resistant carbapenemase-producing Klebsiella represents a therapeutic challenge and a worldwide problem. Aim: To estimate the in-hospital mortality and identify the associated risk factors among patients with colistin-resistant carbapenemase-producing Klebsiella pneumoniae (KPC) that present with a clinical infection. Methods: We carried a retrospective cohort study, including adult patients infected with colistin-resistant KPC hospitalized at a tertiary teaching hospital in Buenos Aires, Argentina during the year 2016. The main outcome was in-hospital mortality. We used generalized lineal models to evaluate potential predictors of mortality. Results: 18 patients that developed a colistin-resistant KPC clinical infection were identified and included in the final analysis. In-hospital mortality in this cohort was 38.9%. The presence of bacteremia, acute renal injury at the time of diagnosis and septic shock were associated with the main outcome. Conclusions: Infections due to colistin-resistant KPC among in-hospital patients was frequent and was associated with high mortality rate. In our cohort, both shock and acute kidney injury were associated with a higher likelihood of poor outcomes. Further studies are warranted to evaluate the role of these and others risk factors so as to aid in the early detection of high risk patients.

Klebsiella pneumoniae multi-resistente, factores predisponentes y mortalidad asociada en un hospital universitario en Colombia / Multidrug-resistant Klebsiella pneumoniae, predisposing factors and associated mortality in a tertiary-care hospital in Colombia

Introduction: Bacterial resistance to antibiotics is a serious public health problem that is increasing worldwide. Resistant (R) Klebsiella pneumoniae is one of the main pathogens isolated in nosocomial infections. The aim of this study was to explore risk factors associated with the acquisition of infection by R-K. pneumoniae and mortality. Methods: Prospective cohort study conducted in a hospital of high complexity of Medellin, October/2009-April/2010. The exposed group was defined as patients infected with R-K. pneumoniae (producing b-lactamases or carbapenemases). In order to identify risk factors associated with infection by R-K. pneumoniae and 30 day mortality, logistic regression and Cox proportional hazards regression were used. Results: 243 patients were included in the study, 84 infected with R-K. pneumoniae and 159 infected with susceptible K. pneumoniae. Female sex (OR = 2.51 95% 1.37 to 4.6), the co-existence of cardiovascular disease (OR = 2.13 95% CI 1.14 to 3.99), previous use of ceftriaxone (OR = 9.52 95% CI 2.63 to 34.46) and carbapenems (OR = 4.23 95% CI 2.41 to 7.42) were risk factors associated to infection with R-K. pneumoniae. Some predictors of mortality were malignant neoplasia (HR = 4.43 95% CI 2.13 to 9.22) and mechanical ventilation (HR = 3.81 95% CI 1.99 to 7.28). There was no difference in 30-day mortality when comparing patients in both groups. Conclusions: Female gender, cardiovascular disease and previous use of antimicrobials were associated with infection by R-K. pneumoniae. Thirty-day mortality was similar in both groups of patients.

Introducción: La resistencia bacteriana a antimicrobianos es un grave problema de salud pública que va aumentando en el mundo. Klebsiella pneumoniae resistente (R) es uno de los principales patógenos aislado en infecciones hospitalarias. El objetivo de este estudio fue explorar factores de riesgo asociados con la adquisición de infección por K. pneumoniae R y con mortalidad. Metodología: Estudio de cohorte prospectivo realizado en un hospital de alta complejidad de Medellín, octubre/2009-abril/2010. El grupo expuesto se definió como pacientes infectados por K. pneumoniae R (productora de β-lactamasas de espectro extendido o carbapenemasas). Se hicieron regresión logística para identificar los factores de riesgo asociados con infección por K. pneumoniae R, y regresión de riesgos proporcionales de Cox para identificar los factores asociados con mortalidad a 30 días. Resultados: Se incluyeron 243 pacientes al estudio, 84 infectados con K. pneumoniae R y 159 con K. pneumoniae sensible.El sexo femenino (OR = 2,51 IC95% 1,37-4,6), la co-existencia de enfermedad cardiovascular (OR = 2,13 IC 95% 1,14-3,99), uso previo de ceftriaxona (OR = 9,52 IC95% 2,63-34,46) y carbapenémicos (OR = 4,23 IC95% 2,41-7,42) fueron factores de riesgo asociados con la probabilidad de infectarse por K. pneumoniae R. Algunos factores predictores de mortalidad fueron las neoplasias malignas (HR = 4,43 IC95% 2,13-9,22) y la ventilación mecánica (HR = 3,81 IC95% 1,99-7,28). No hubo diferencia en la mortalidad a 30 días al comparar los pacientes de ambos grupos. Conclusiones: El sexo femenino, la enfermedad cardiovascular y el uso previo de antimicrobianos se vieron asociados con infección por K. pneumoniae R. La mortalidad a 30 días fue similar en ambos grupos de pacientes.

Klebsiella ESBL bacteremia-mortality and risk factors

Background: Extended spectrum β-lactamase (ESBL)-producing bacteria have become recognized as a problem in South America. The aim of this study was to evaluate risk factors and mortality rate in bacteremia caused by ESBL-producing Klebsiella pneumoniae in a Brazilian hospital. Methods: A three-year retrospective cohort study with 104 cases of K. pneumoniae bacteremia (61 ESBL and 43 non-ESBL). Several clinical and laboratory variables were evaluated. The outcome of interest was 30-day mortality. The adequate treatment was evaluated according to antibiotic susceptibility. Results: Multivariable analysis showed that central venous catheter and mechanical ventilation were independent risk factors for ESBL. The duration of hospitalization before the bacteremia was not a risk factor. Mortality was similar in ESBL and non-ESBL and inadequate therapy was not shown to be a risk factor. Conclusion: ESBL-producing Klebsiella bacteremia can occur early, suggesting that a carbapenem should be included in the initial empirical therapy for bacteremia in patients under mechanical ventilation and/or central venous catheter in our institution.

Risk factors for and mortality of extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli nosocomial bloodstream infections / Fatores de risco e mortalidade de infecções da corrente sanguínea por Klebsiella pneumoniae and Escherichia coli produtores de beta-lactamase de espectro estendido

A case-control study, involving patients with positive blood cultures for Klebsiella pneumoniae (KP) or Escherichia coli (EC) EC and controls with positive blood cultures for non-ESBL-KP or EC, was performed to assess risk factors for extended-spectrum-β-lactamase (ESBL) production from nosocomial bloodstream infections (BSIs). Mortality among patients with BSIs was also assessed. The study included 145 patients (81, 59.5 percent with K. pneumoniae and 64, 44.1 percent with E. coli BSI); 51 (35.2 percent) isolates were ESBL producers and 94 (64.8 percent) nonproducers. Forty-five (55.6 percent) K. pneumoniae isolates were ESBL producers, while only six (9.4 percent) E. coli isolates produced the enzyme. Multivariate analysis showed that recent exposure to piperacillin-tazobactam (adjusted Odds Ratio [aOR] 6.2; 95 percentCI 1.1-34.7) was a risk factor for ESBL BSI. K. pneumoniae was significantly more likely to be an ESBL-producing isolate than E. coli (aOR 6.7; 95 percentCI 2.3-20.2). No cephalosporin class was independently associated with ESBLs BSI; however, in a secondary model considering all oxymino-cephalosporins as a single variable, a significant association was demonstrated (aOR 3.7; 95 percentCI 1.3-10.8). Overall 60-day mortality was significantly higher among ESBL-producing organisms. The finding that piperacillin-tazobactam use is a risk factor for ESBL-production in KP or EC BSIs requires attention, since this drug can be recommended to limit the use of third-generation cephalosporins.

Estudo de caso-controle, onde os casos foram pacientes com hemocultura positiva para Klebsiella pneumoniae (KP) ou Escherichia coli (EC) produtores de beta lactamase de espectro estendido (ESBL) e os controles foram pacientes com hemoculturas positivas para EC ou KP não produtores de ESBL foi realizado para avaliar os fatores de risco para produção destas enzimas em infecções da corrente sanguínea (ICS). Mortalidade dos pacientes com ICS também foi avaliada. Foram incluídos 145 pacientes (81, 59,5 por cento tinham Klebsiella pneumoniae e 64, 44,1 por cento tinham Escherichia coli); 51 (35,2 por cento) isolados eram produtores de ESBL e 94 (64,8 por cento) eram não produtores. Quarenta e cinco (55,6 por cento) isolados de K. pneumoniae e somente seis (9,4 por cento) isolados de E. coli eram produtores de ESBL. Análise multivariada mostrou que exposição recente a piperacilina-tazobactam (OR ajustado [aOddsRatio] 6,2; 95 por cento Intervalo de Confiança [IC] 1,1-34,7) foi fator de risco para infecção da corrente sanguínea por ESBL. Foi significativamente maior a chance de K. pneumoniae ser um isolado produtor de ESBL do que E. coli o ser (aOR 6,7; 95 por cento CI 2,3-20,2). Nenhuma classe de cefalosporina foi independentemente associada com ESBL-ICS. No entanto, em um modelo secundário considerando todas as oximino-cefalosporinas como variável única, foi demonstrada associação significativa (aOR 3,7; 95 por cento IC 1,3-10,8). Mortalidade total em 60 dias foi significativamente maior entre isolados produtores de ESBL. O achado de piperacilina-tazobactam como fator de risco para produção de ESBL em ICS por KP ou EC requer atenção, uma vez que esta droga tem sido eventualmente recomendada para poupar o uso de cefalosporinas de terceira geração.

Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis

This study tested the hypothesis that the use of corticosteroids prior to antibiotics can lower the mortality rate in severe infections by S. aureus or Gram-negative bacilli, using an animal model. This study was a prospective and controlled study, placed in a university laboratory. Seven hundred and sixty mice distributed into three groups (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae infected). The interventions in each group were: I) infection control (intra-peritoneal); II) treatment solely with antibiotics (teicoplanin or amikacin); III) antibiotics administered prior to the corticosteroid (methylprednisolone); IV) antibiotics administered after the corticosteroid. Mortality in the E. coli group, subgroup I: 100 percent; subgroup II: 55 percent (p<0.001); subgroup III: 62.5 percent (p=0.2488, compared to subgroup II); subgroup IV: 20 percent (p<0.01 compared to subgroups II and III). Mortality in the K. pneumoniae group: subgroup I: 100 percent; subgroup II: 72.5 percent (p<0.01); subgroup III: 80 percent (p=0.215 compared to subgroup II); subgroup IV: 45 percent (p<0.01 compared to subgroups II and III). Mortality in the S. aureus group: subgroup I: 82.5 percent; II: 42.5 percent (p<0.001); subgroup III: 77.5 percent (p=0.2877 compared to subgroup I); subgroup IV: 32.5 percent (p=0.1792 compared to subgroup II). The use of corticosteroids prior to antibiotics lowered the mortality rate caused by Gram-negative bacteria and did not affect the mortality caused by S. aureus. When used after starting treatment with antibiotics, the corticosteroid was not superior to the use of antibiotics alone in the case of the Gram-negative bacteria, and was not significantly different from non-treatment of the infection, in the case of S. aureus.

Clinical outcome and risk factors related to extended-spectrum beta-lactamase-producing Klebsiella spp. infection among hospitalized patients

Over the past two decades, nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. have become a major problem all around the world. This situation is of concern because there are limited antimicrobial options to treat patients infected with these pathogens, and also because this kind of resistance can spread to a wide variety of Gram-negative bacilli. Our objectives wereto evaluate among in-patients at a publicuniversity tertiary-care hospital with documented infection due to Klebsiella spp., which were the risk factors (cross-sectional analysis) and the clinical impact (prospective cohort) associated with an ESBL-producing strain. Study subjects were all patients admitted at the study hospital between April 2002 and October 2003, with a clinically and microbiologically confirmed infection caused by Klebsiella spp. at any body site, except infections restricted to the urinary tract. Of the 104 patients studied, 47 were infected with an ESBL-producing strain and 57 with a non-ESBL-producing strain. Independent risk factors associated with infection with an ESBL-producing strain were young age, exposure to mechanical ventilation, central venous catheter, use of any antimicrobial agent, and particularly use of a 4th generation cephalosporin or a quinolone. Length of stay was significant longer for patients infected with ESBL-producing strains than for those infected with non-ESBL-producing strains, although fatality rate was not significantly affected by ESBL-production in this cohort. In fact, mechanical ventilation and bacteremia were the only variables withindependent association withdeath detected in this investigation.