Risk factors and survival of patients infected with carbapenem-resistant Klebsiella pneumoniae in a KPC endemic setting: a case-control and cohort study.

BACKGROUND: Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy. METHODS: A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy. RESULTS: A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37). CONCLUSION: Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.

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

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 48h of diagnosing bacteremia. Delayed administration was considered when polymyxin B was administered after 48h 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; 1306.52mg versus 1247.06mg, 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).

Combination therapy with polymyxin B for carbapenemase-producing Klebsiella pneumoniae bloodstream infection.

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) bloodstream infections (BSIs) are related to high mortality rates, and combination therapy has been associated with lower mortality in patients treated mostly with colistin. There is a paucity of studies addressing polymyxin B (PMB) treatment for KPC-KP infections. This was a retrospective cohort study of patients with monomicrobial KPC-KP BSIs. The primary outcome was 30-day mortality. Antimicrobial therapy was defined as empirical (started within the first 48 h) or definitive (initiated after >48 h) and was evaluated as follows: monotherapy (only one in vitro active agent or combination therapy of one in vitro active agent plus one or more in vitro non-active agents); and combination therapy with two or more in vitro active agents. A total of 82 KPC-KP BSIs were included; 40 patients (48.8%) died in the first 30 days. Mortality of patients treated with the combination of two in vitro active antimicrobial agents, mostly PMB plus amikacin, was significantly lower (37.5%) compared with monotherapy (64.7%) (P= 0.01). Combination therapy [adjusted hazard ratio (aHR) = 0.40, 95% confidence interval (CI) 0.22-0.83; P = 0.01] was independently associated with lower 30-day survival when controlled for non-surgical admission (aHR = 2.33, 95% CI 1.14-4.80; P = 0.02) and use of vasoactive drugs (aHR = 7.37, 95% CI 3.01-18.02; P < 0.01). In conclusion, combination therapy with two in vitro active agents, mostly PMB plus amikacin, showed a survival benefit compared with other regimens.

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).

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

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.

Association of Colistin-Resistant KPC Clonal Strains with Subsequent Infections and Colonization and Biofilm Production.

Carbapenemase-producing organisms are pandemic and a significant threat to public health. We investigated the clonal relatedness of colistin-resistant Klebsiella pneumoniae strains producing KPC-type carbapenemase (KPC-KP) causing subsequent infections or colonization. Moreover, we aimed to gain insight into the ability of biofilm production in K. pneumoniae strains producing carbapenemase. Twenty-two consecutive KPC-KP and one KPC-negative strain was identified from an adult intensive care unit in Brazil. Seventy-five percent of isolates that harbored the blaKPC gene exhibited genetic relatedness by pulsed-field gel electrophoresis, and none presented the plasmid-mediated mcr-1 and blaNDM genes. This study showed that the majority of repeated KPC infections in adults were caused by a clone that caused the previous infections/colonizations even after a long period of time and illustrates the capacity of multiple clones producing biofilms to coexist in the same patient at the same time, becoming a reservoir of KPC-KP in the hospital environment.

Mortality due to KPC carbapenemase-producing Klebsiella pneumoniae infections: Systematic review and meta-analysis: Mortality due to KPC Klebsiella pneumoniae infections.

INTRODUCTION: KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) has become a major public health challenge. Accordingly, this study sought to use a systematic review of the scientific literature to ascertain the mortality of KPC-KP infection, and analyze such mortality by country, year of publication, hospital ward, and type of interpretation used to define carbapenem resistance. METHODOLOGY: A search without language restrictions was made of the MEDLINE, CENTRAL, EBSCO, LILACS and EMBASE databases from 1996 through June 2017, to locate all studies which had determined the existence of KPC-KP infection. We then performed a meta-analysis of all studies that reported KPC-KP infection-related mortality, and analyzed mortality by subgroup in accordance with standard methodology. RESULTS: A total of 51 papers were included in the systematic review. From 2005 through 2017, data on KPC-KP infection were reported in 5124 patients, with an average of 465 patients per year. The most widely studied type of infection was bacteremia (28∙0%). The meta-analysis showed that overall mortality for the 37 studies was 41.0% (95%CI 37.0-44.0), with the highest mortality rates being observed in oncology patients, 56.0% (95%CI 38.1-73.0), and Brazil, 51.3% (95%CI 43.0-60.0). CONCLUSION: KPC-KP infection-related mortality is high, is manifested differently in some countries, and is highest among oncology patients.

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.

Acinetobacter spp. are associated with a higher mortality in intensive care patients with bacteremia: a survival analysis.

BACKGROUND: It has been challenging to determine the true clinical impact of Acinetobacter spp., due to the predilection of this pathogen to colonize and infect critically ill patients, who often have a poor prognosis. The aim of this study was to assess whether Acinetobacter spp. bacteremia is associated with lower survival compared with bacteremia caused by other pathogens in critically ill patients. METHODS: This study was performed at Hospital das Clínicas, University of São Paulo, Brazil. There are 12 intensive care units (ICUs) in the hospital: five Internal Medicine ICUs (emergency, nephrology, infectious diseases and respiratory critical care), three surgical ICU (for general surgery and liver transplantion), an Emergency Department ICU for trauma patients, an ICU for burned patients, a neurosurgical ICU and a post-operative ICU. A retrospective review of medical records was conducted for all patients admitted to any of the ICUs, who developed bacteremia from January 2010 through December 2011. Patients with Acinetobacter spp. were compared with those with other pathogens (Klebsiella pneumoniae, Staphylococcus aureus, Enterobacter spp., Enterococcus spp., Pseudomonas aeruginosa). We did a 30-day survival analysis. The Kaplan-Meier method and log-rank test were used to determine the overall survival. Potential prognostic factors were identified by bivariate and multivariate Cox regression analysis. RESULTS: One hundred forty-one patients were evaluated. No differences between patients with Acinetobacter spp. and other pathogens were observed with regard to age, sex, APACHE II score, Charlson Comorbidity Score and type of infection. Initial inappropriate antimicrobial treatment was more frequent in Acinetobacter bacteremia (88 % vs 51 %). Bivariate analysis showed that age > 60 years, diabetes mellitus, and Acinetobacter spp. infection were significantly associated with a poor prognosis. Multivariate model showed that Acinetobacter spp. infection (HR = 1.93, 95 % CI: 1.25-2.97) and age > 60 years were independent prognostic factors. CONCLUSION: Acinetobacter is associated with lower survival compared with other pathogens in critically ill patients with bacteremia, and is not merely a marker of disease severity.

Activity of antimicrobial combinations against KPC-2-producing Klebsiella pneumoniae in a rat model and time-kill assay.

This study evaluated the efficacy of tigecycline (TIG), polymyxin B (PMB), and meropenem (MER) in 80 rats challenged with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae infection. A time-kill assay was performed with the same strain. Triple therapy and PMB+TIG were synergistic, promoted 100% survival, and produced negative peritoneal cultures, while MER+TIG showed lower survival and higher culture positivity than other regimens (P = 0.018) and was antagonistic. In vivo and in vitro studies showed that combined regimens, except MER+TIG, were more effective than monotherapies for this KPC-producing strain.

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in cancer patients.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is an emergent pathogen in healthcare-associated infections (HAIs). The aim of this study was to describe HAIs due to KPC-Kp, as well as identify mortality risk factors in cancer patients. In patients diagnosed with HAIs due to KPC-Kp between January 2009 and July 2013, we evaluated only the first infection episode of each patient, analyzing mortality separately for patients treated for ≥48 h with at least one antimicrobial agent proven to display in vitro activity against KPC-Kp. We evaluated variables related to the malignancy, the severity and characteristics of the HAI, and the antimicrobial therapy. We identified 83 HAIs due to KPC-Kp. The 30-day mortality was 57.8 % for all infections and 72.7 % for bacteremic infections. Of the 83 patients, 60 patients received ≥48 h of appropriate treatment and 44 (53 %) developed bacteremia. Ten patients (12 %) were neutropenic at HAI diagnosis and 33 (39.8 %) had infection at the tumor site. The most common HAI was urinary tract infection, seen in 26 patients (31.3 %), followed by primary bloodstream infection, seen in 24 patients (28.9 %). Forty-four patients (73.3 %) received combination antimicrobial therapy, most often including polymyxin (68.3 %). Risk factors for 30-day mortality are high sequential organ failure assessment (SOFA) score, need for intensive care stay at diagnosis of infection, and acute kidney injury; the removal of invasive devices related to infection and treatment with effective antibiotics for KPC-Kp are protective factors. In cancer patients, high mortality is associated with HAI due to KPC-Kp and mortality risk factors are more often related to acute infection than to the underlying disease.

Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients.

We conducted a retrospective study of 17 transplant recipients with carbapenem-resistant Klebsiella pneumoniae bacteremia, and described epidemiology, clinical characteristics and strain genotypes. Eighty-eight percent (15/17) of patients were liver or intestinal transplant recipients. Outcomes were death due to septic shock (18%), cure (24%) and persistent (>7 days) or recurrent bacteremia (29% each). Thirty- and 90-day mortality was 18% and 47%, respectively. Patients who were cured received at least one active antimicrobial agent and underwent source control interventions. Forty-one percent (7/17) of patients had intra-abdominal infections; all except one developed persistent/recurrent bacteremia despite drainage. Two patients tolerated persistent bacteremia for >300 days. All patients except one were infected with sequence type 258 (ST258), K. pneumoniae carbapenemase (KPC)-2-producing strains harboring a mutant ompK35 porin gene; the exception was infected with an ST37, KPC-3-producing strain. Seventy-one percent (12/17) of patients were infected with ST258 ompK36 mutant strains. In two patients, persistent bacteremia was caused by two strains with different ompK36 genotypes. Three ompK36 mutations were associated with significantly higher carbapenem minimum inhibitory concentrations than wild-type ompK36. Pulse-field gel electrophoresis identified a single ST258 lineage; serial strains from individual patients were indistinguishable. In conclusion, KPC-K. pneumoniae bacteremia exhibited highly diverse clinical courses following transplantation, and was caused by clonal ST258 strains with different ompK36 genotypes.

A hospital-based matched case-control study to identify clinical outcome and risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection.

BACKGROUND: Healthcare-associated infections caused by Klebsiella pneumoniae isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among K. pneumoniae isolated from patients at a tertiary private hospital that showed a phenotype compatible with carbapenemase production although this group of enzymes was not detected in any sample. The aim of this study was to describe the epidemiology and clinical outcomes associated with carbapenem-resistant K. pneumoniae and to determine the antimicrobial resistance mechanisms. METHODS: Risk factors associated with carbapenem-resistant K. pneumoniae infections were investigated by a matched case-control study from January 2006 through August 2008. A cohort study was also performed to evaluate the association between carbapenem resistance and in-hospital mortality. Bacterial identification and antimicrobial susceptibility were determined by Vitek 2 and Etest. Carbapenemase activity was detected using spectrophotometric assays. Production of beta-lactamases and alterations in genes encoding K. pneumoniae outer membrane proteins, OmpK35 and OmpK36, were analyzed by PCR and DNA sequencing, as well as SDS-Page. Genetic relatedness of carbapenem resistant isolates was evaluated by Pulsed Field Gel Electrophoresis. RESULTS: Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant K. pneumoniae infections compared with those with carbapenem-susceptible K. pneumoniae (50.0% vs 25.7%). The length of central venous catheter use was independently associated with carbapenem resistance in the multivariable analysis. All strains, except one, carried blaCTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed blaGES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected. CONCLUSIONS: The K. pneumoniae multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased K. pneumoniae carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presence of the insertion sequences in the outer membrane encoding genes.

Pneumonia-induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters.

The aim of the present work is to provide a better comprehension of the pneumonia-induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-α and IL-1ß levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.

An outbreak of Klebsiella pneumoniae late-onset sepsis in a neonatal intensive care unit in Guatemala.

BACKGROUND: Gram-negative bloodstream infections are an important cause of neonatal mortality. In October 2009, we investigated a Klebsiella spp outbreak in a neonatal intensive care unit in Guatemala. METHODS: Probable cases were defined as a Klebsiella spp isolated from blood in neonates aged <28 days in the neonatal intensive care unit between October 1 and November 10, 2009; confirmed cases were identified as Klebsiella pneumoniae. Clinical data were abstracted from medical charts. K pneumoniae isolates were genotyped by pulsed-field gel electrophoresis (PFGE) and tested for antimicrobial susceptibility. Infection control practices were inspected. RESULTS: There were 14 confirmed cases. The median age at onset of infection was 3 days (range, 2-8 days). Nine patients died (64%). K pneumoniae isolates were resistant to multiple antimicrobials. PFGE revealed 2 distinct clusters. Breaches in infection control procedures included inappropriate intravenous solution use and inadequate hand hygiene and contact precautions. CONCLUSIONS: We report a K pneumoniae outbreak with high neonatal mortality in Guatemala. PFGE clustering suggested a common source possibly related to reuse of a single-use intravenous medication or solution. The risk for K pneumoniae bloodstream infections in neonates in low-resource settings where sharing of solutions is common needs to be emphasized.

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

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.

Intercontinental spread from Israel to Colombia of a KPC-3-producing Klebsiella pneumoniae strain.

In 2008, an increase in the prevalence of carbapenem-resistant Klebsiella pneumoniae was noted in a 286-bed tertiary case hospital in Colombia, where 84 patients (32 infected and 52 colonized) had positive cultures. The identified index patient came from Israel for a liver transplantation. High level carbapenem resistance was observed. Polymyxin B and tigecycline were the only two antibiotics that remained active. PCR-restriction fragment length polymorphism analysis and sequencing revealed blaKPC-3 in the major clone, which was indistinguishable from the K. pneumoniae carbapenemase-3-producing clone described previously in Israel. This exemplifies the threat posed by the global spread of K. pneumoniae carbapenemase-producing pathogens.

Klebsiella ESBL bacteremia-mortality and risk factors.

BACKGROUND: Extended spectrum ß-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.