Mortalidad y desenlaces clínicos en pacientes críticamente enfermos con infecciones por bacterias productoras de carbapenemasas en un hospital de alta complejidad en Bogotá, Colombia / Mortality and clinical outcomes in critically ill patients with carbapenemase-producing bacteria in a tertiary-care hospital in Bogotá, Colombia

Resumen Introducción: Los microorganismos capaces de producir carbapenemasas vienen incrementándose a nivel mundial y se han convertido en un problema de salud pública global. En Colombia actualmente la resistencia a carbapenémicos en las unidades de cuidado intensivo está aumentando y se desconoce su impacto en desenlaces clínicos. Objetivos: Determinar las características demográficas, clínicas, y los desenlaces de los pacientes adultos en estado crítico con infección por microorganismos productores de carbapenemasas en una unidad de cuidado intensivo polivalente de una institución de alta complejidad. Métodos: Estudio observacional, descriptivo y retrospectivo, incluyendo pacientes con infección por bacterias resistentes a carbapenémicos, ingresados a la unidad de cuidado intensivo entre el 1 de Enero de 2014 y el 1 de Enero de 2018. Se excluyeron los pacientes colonizados. Se evaluaron complicaciones clínicas, estancia en UCI y hospitalaria, así como la mortalidad en UCI y hospitalaria. Resultados: Se incluyó 58 pacientes. La mortalidad global fue de 67,2%, de los cuales 55,17% murió durante su estancia en la unidad de cuidado intensivo y 12.06% en hospitalización. La mediana de estancia en la unidad de cuidado intensivo fue de 18 días (RIQ 4-28). La causa más frecuente de mortalidad fue choque séptico en 51% y las complicaciones más comunes fueron lesión renal aguda y delirium en un 55,2% y 43,1%, respectivamente. La mediana de estancia en la UCI fue de 18 días (RIQ 4-28). Conclusiones: Las infecciones por bacterias resistentes a carbapenémicos en pacientes críticamente enfermos se relacionan con altas tasas de mortalidad, complicaciones y estancia prolongada en UCI

Abstract Introduction: Microorganisms able to produce carbapenemases are spreading worldwide and have become a concerning global public-health problem. In Colombia, the Gram-negative resistance to carbapenems at intensive care units is currently increasing and its impact on clinical outcomes is not well known. Objectives: To determine the demographic, clinical characteristics and outcomes of critically ill adult patients with infection by carbapenemase producing bacteria in a polyvalent intensive care unit of a highly complex institution. Methods: Single-center retrospective, descriptive observational study including critically ill adult patients infected by carbapenemase-producing bacteria and transferred to a polyvalent intensive care unit from January 1th 2014 to January 1th 2018. Known colonized patients were excluded. Clinical complications, ICU and in-hospital days of stay were evaluated, as ICU and in-hospital mortality. Results: A total of 58 patients were included. Overall mortality was 67.2%, of which 55.17% died during their stay in the intensive care unit and 12.06% in hospitalization. The median stay in the intensive care unit was 18 days (IQR 4-28). The most frequent cause of death was septic shock in 51% and the most common complications were acute renal injury and delirium in 55.2% and 43.1%, respectively. The median stay in the ICU was 18 days (RIQ 4-28). Conclusions: Infections caused by carbapenem-resistant bacteria in critically ill patients are associated with high mortality rates, complications and long stay in ICU.

Costos médicos directos de las infecciones del tracto urinario por bacilos Gram negativos resistentes a betalactámicos en un hospital de alta complejidad de Medellín, Colombia / Direct medical costs of urinary tract infections by Gram-negative bacilli resistant to beta-lactams in a tertiary care hospital in Medellín, Colombia

Resumen Introducción. Las infecciones del tracto urinario son muy frecuentes en el ámbito hospitalario. Debido a la aparición de la resistencia antimicrobiana, la complejidad de los procesos de atención ha aumentado y, con ello, la demanda de recursos. Objetivo. Describir y comparar el exceso de los costos médicos directos de las infecciones del tracto urinario por Klebsiella pneumoniae, Enterobacter cloacae y Pseudomonas aeruginosa resistentes a betalactámicos. Materiales y métodos. Se llevó a cabo un estudio de cohorte en una institución de tercer nivel de Medellín, Colombia, entre octubre del 2014 y septiembre del 2015. Se incluyeron los pacientes con infección urinaria, unos por bacterias sensibles a los antibióticos betalactámicos, y otros por bacterias resistentes a las cefalosporinas de tercera y cuarta generación y a los antibióticos carbapenémicos. Los costos se analizaron desde la perspectiva del sistema de salud. La información clínico-epidemiológica se obtuvo de las historias clínicas y los costos se calcularon utilizando los manuales tarifarios estándar. El exceso de costos se estimó mediante análisis multivariados. Resultados. Se incluyeron 141 pacientes con infección urinaria: 55 (39 %) por bacterias sensibles a los betalactámicos, 54 (38,3 %) por bacterias resistentes a las cefalosporinas y 32 (22,7 %) por bacterias resistentes a los carbapenémicos. El exceso de costos totales ajustado de los 86 pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas y a los carbapenémicos, fue de USD$ 193 (IC95% -347 a 734) y USD$ 633 (IC95% -50 a 1.316), respectivamente comparados con el grupo de 55 pacientes por bacterias sensibles a los betalactámicos. Las diferencias se presentaron principalmente en el uso de antibióticos de amplio espectro, como el meropenem, la colistina y la fosfomicina. Conclusión. Los resultados evidenciaron un incremento sustancial de los costos médicos directos de los pacientes con infecciones del tracto urinario por bacterias resistentes a las cefalosporinas o a los carbapenémicos. Esta situación genera especial preocupación en los países endémicos como Colombia, donde la alta frecuencia de infecciones del tracto urinario y de resistencia a los betalactámicos puede causar un mayor impacto económico en el sector de la salud.

Abstract Introduction: Urinary tract infections are very frequent in the hospital environment and given the emergence of antimicrobial resistance, they have made care processes more complex and have placed additional pressure on available healthcare resources. Objective: To describe and compare excess direct medical costs of urinary tract infections due to Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa resistant to beta-lactams. Materials and methods: A cohort study was conducted in a third level hospital in Medellín, Colombia, from October, 2014, to September, 2015. It included patients with urinary tract infections caused by beta-lactam-susceptible bacteria, third and fourth generation cephalosporin-resistant, as well as carbapenem-resistant. Costs were analyzed from the perspective of the health system. Clinical-epidemiological information was obtained from medical records and the costs were calculated using standard tariff manuals. Excess costs were estimated with multivariate analyses. Results: We included 141 patients: 55 (39%) were sensitive to beta-lactams, 54 (38.3%) were resistant to cephalosporins and 32 (22.7%) to carbapenems. The excess total adjusted costs of patients with urinary tract infections due to cephalosporin- and carbapenem-resistant bacteria were US$ 193 (95% confidence interval (CI): US$ -347-734) and US$ 633 (95% CI: US$ -50-1316), respectively, compared to the group of patients with beta-lactam sensitive urinary tract infections. The differences were mainly found in the use of broad-spectrum antibiotics such as meropenem, colistin, and fosfomycin. Conclusion: Our results show a substantial increase in the direct medical costs of patients with urinary tract infections caused by beta-lactam-resistant Gram-negative bacilli (cephalosporins and carbapenems). This situation is of particular concern in endemic countries such as Colombia, where the high frequencies of urinary tract infections and the resistance to beta-lactam antibiotics can generate a greater economic impact on the health sector.

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.

Risk factors for infection with carbapenem-resistant Klebsiella pneumoniae: a case-case-control study / Factores de riesgo para infección con Klebsiella pneumoniae resistente a carbapenémicos: estudio caso-caso-control

Objective: To evaluate the association between quinolone exposure and the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and to estimate CRKP-specific mortality. Methods: Case-case-control study implemented in a tertiary care institution. Three groups of patients were analyzed: 61 consecutive cases of infection with CRKP (Group I); 61 randomly chosen cases of patients infected with carbapenem-sensitive Klebsiella pneumoniae (CSKP; Group II); and 122 randomly chosen controls without CRKP or CSKP infection. Matching was based on the length of stay in intensive care unit and the date of bacterial isolation. An active search was performed for patients with CRKP and CSKP infection, and prospective cases were included in the study. We compared the results for Groups I and II against those for the controls by using two conditional logistic regression analyses that included infection as the dependent variable and controlled for time at risk and co-morbidities. Results: Exposure to quinolones was not associated with CRKP infection: no association was found in the analysis of CRKP with the controls (OR = 1.7; 95% CI: 0.2-6.5) or in the analysis of CSKP against the controls (OR = 0.6; 95% CI: 0.2-1.6). Use of carbapenems (OR = 3.3; 95% CI: 1.2-9.3) and colonization with CRKP (OR = 3.3; 95% IC: 1.2-9.3) were specific risk factors for infection with CRKP. Mortality associated with CRKP was 61.3%. Conclusion: No association was found between exposure to quinolones and infection with CRKP; however, colonization by CRKP and use of carbapenems are risk factors for infection with CRKP.

Resumen Objetivo: Evaluar la asociación entre la exposición a quinolonas y la aparición de infección por Klebsiella pneumoniae resistente a Carbapenémicos (CRKP) y estimar la mortalidad específica por CRKP. Métodos: Estudio caso-caso-control realizado en una institución de tercer nivel de atención. Se adelantó búsqueda activa y prospectiva de los casos. Se analizaron tres grupos: 61 casos consecutivos de infección por CRKP, 61 casos elegidos al azar de los pacientes con infección por Klebsiella pneumoniae sensible a Carbapenémicos (CSKP) y 122 controles sin infección por CRKP ni por CSKP, elegidos al azar. Se realizó emparejamiento por estancia en unidad de cuidados intensivos y fecha del aislamiento bacteriano. Los datos se extractaron de la historia clínica electrónica. Se comparó los casos CRKP y los casos CSKP contra los controles mediante dos análisis de regresión logística condicional, con la infección como variable dependiente y controlando por el tiempo en riesgo y la comorbilidad. Resultados: La exposición a quinolonas no se asoció a infección con CRKP: no se encontró asociación en el análisis de CRKP contra controles (OR 1.7 IC 95%: 0.2-6.5) ni en el análisis de CSKP contra controles (OR 0.6 IC 95%: 0.2-1.6). El uso de carbapenémicos (OR 3.3 IC 95%: 1.2-9.3) y la colonización por KPRC (OR 16,2 IC 95%: IC 95%: 3.3-79.1) fueron factores de riesgo específicos para infección por CRKP. La mortalidad específica asociada a CRKP fue de 61.3%. Conclusión: No se encontró asociación entre la exposición a quinolonas y la infección por KPRC, pero la colonización por CRKP y el uso de carbapenémicos son factores de riesgo asociados a la infección por KPRC.

Risk factors for infection with multidrug-resistant bacteria in non-ventilated patients with hospital-acquired pneumonia / Fatores de risco para multirresistência bacteriana em pneumonias adquiridas no hospital não associadas à ventilação mecânica

OBJECTIVE: To identify risk factors for the development of hospital-acquired pneumonia (HAP) caused by multidrug-resistant (MDR) bacteria in non-ventilated patients. METHODS: This was a retrospective observational cohort study conducted over a three-year period at a tertiary-care teaching hospital. We included only non-ventilated patients diagnosed with HAP and presenting with positive bacterial cultures. Categorical variables were compared with chi-square test. Logistic regression analysis was used to determine risk factors for HAP caused by MDR bacteria. RESULTS: Of the 140 patients diagnosed with HAP, 59 (42.1%) were infected with MDR strains. Among the patients infected with methicillin-resistant Staphylococcus aureus and those infected with methicillin-susceptible S. aureus, mortality was 45.9% and 50.0%, respectively (p = 0.763). Among the patients infected with MDR and those infected with non-MDR gram-negative bacilli, mortality was 45.8% and 38.3%, respectively (p = 0.527). Univariate analysis identified the following risk factors for infection with MDR bacteria: COPD; congestive heart failure; chronic renal failure; dialysis; urinary catheterization; extrapulmonary infection; and use of antimicrobial therapy within the last 10 days before the diagnosis of HAP. Multivariate analysis showed that the use of antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria (OR = 3.45; 95% CI: 1.56-7.61; p = 0.002). CONCLUSIONS: In this single-center study, the use of broad-spectrum antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria in non-ventilated patients with HAP. .

OBJETIVO: Identificar fatores de risco para o desenvolvimento de pneumonia adquirida no hospital (PAH), não associada à ventilação mecânica e causada por bactérias multirresistentes (MR). MÉTODOS: Estudo de coorte observacional retrospectivo, conduzido ao longo de três anos em um hospital universitário terciário. Incluímos apenas pacientes sem ventilação mecânica, com diagnóstico de PAH e com cultura bacteriana positiva. Variáveis categóricas foram comparadas por meio do teste do qui-quadrado. A análise de regressão logística foi usada para determinar os fatores de risco para PAH causada por bactérias MR. RESULTADOS: Dos 140 pacientes diagnosticados com PAH, 59 (42,1%) apresentavam infecção por cepas MR. As taxas de mortalidade nos pacientes com cepas de Staphylococcus aureus resistentes e sensíveis à meticilina, respectivamente, foram de 45,9% e 50,0% (p = 0,763). As taxas de mortalidade nos pacientes com PAH causada por bacilos gram-negativos MR e não MR, respectivamente, foram de 45,8% e 38,3% (p = 0,527). Na análise univariada, os fatores associados com cepas MR foram DPOC, insuficiência cardíaca crônica, insuficiência renal crônica, diálise, cateterismo urinário, infecções extrapulmonares e uso de antimicrobianos nos 10 dias anteriores ao diagnóstico de PAH. Na análise multivariada, o uso de antimicrobianos nos 10 dias anteriores ao diagnóstico foi o único fator preditor independente de cepas MR (OR = 3,45; IC95%: 1,56-7,61; p = 0,002). CONCLUSÕES: Neste estudo unicêntrico, o uso de antimicrobianos de largo espectro 10 dias antes do diagnóstico de PAH foi o único preditor independente da presença de bactérias MR em pacientes ...

The minimal inhibitory concentration for sulbactam was not associated with the outcome of infections caused by carbapenem-resistant Acinetobacter sp. treated with ampicillin/sulbactam

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome. .

Colonization pressure as a risk factor for colonization by multiresistant Acinetobacter spp and carbapenem-resistant Pseudomonas aeruginosa in an intensive care unit

OBJECTIVE: To determine factors associated with colonization by carbapenem-resistant Pseudomonas aeruginosa and multiresistant Acinetobacter spp. METHODS: Surveillance cultures were collected from patients admitted to the intensive care unit at admission, on the third day after admission and weekly until discharge. The outcome was colonization by these pathogens. Two interventions were implemented: education and the introduction of alcohol rubs. Compliance with hand hygiene, colonization pressure, colonization at admission and risk factors for colonization were evaluated. RESULTS: The probability of becoming colonized increased during the study. The incidence density of colonization by carbapenem-resistant P. aeruginosa and multiresistant Acinetobacter spp. and colonization pressure were different between periods, increasing gradually throughout the study. The increase in colonization pressure was due to patients already colonized at admission. The APACHE II score, colonization pressure in the week before the outcome and male gender were independent risk factors for colonization. Every 1% increase in colonization pressure led to a 2% increase in the risk of being colonized. CONCLUSION: Colonization pressure is a risk factor for carbapenem-resistant P. aeruginosa and multiresistant Acinetobacter spp. colonization. When this pressure reaches critical levels, efforts primarily aimed at hand hygiene may not be sufficient to prevent transmission. .

Risk factors for pan-resistant Pseudomonas aeruginosa bacteremia and the adequacy of antibiotic therapy

INTRODUCTION: The aim of this study was to determine risk factors for acquiring carbapenemresistant Pseudomonas aeruginosa bacteremia (CR-PA) and factors associated with in-hospital mortality. METHODS: Seventy-seven cases of bacteremia caused by P. aeruginosa were evaluated in a hospital with high incidence of CR-PA. Clinical and laboratorial factors, and previous use of antibiotics were also evaluated. In one analysis, CR-PA and carbapenem-susceptible P. aeruginosa (CS-PA) bacteremia were compared. A second analysis compared patients who died with survivors. RESULTS: Among 77 P. aeruginosa bacteremia, 29 were caused by CR-PA. Admission to the intensive care unit, higher number of total leukocytes, and previous use of carbapenem were statistically associated with CR-PA. In the multivariate analysis, only previous use of carbapenem (including ertapenem) turned out to be a risk factor for CR-PA (p = 0.014). The 30-day mortality of patients with P. aeruginosa bloodstream infection was 44.8% for CS-PA and 54.2% for patients with CR-PA (p = 0.288). Chronic renal failure, admission to the intensive care unit, mechanical ventilation, and central venous catheter were risk factors for mortality. Incorrect treatment increased mortality of patients with bacteremia caused by CS-PA, but not for CR-SA. The odd ratio of mortality associated with incorrect therapy in patients with CS-PA was 3.30 (1.01-10.82; p = 0.043). The mortality of patients with bacteremia caused by CR-PA was unexpectedly similar regardless of antimicrobial treatment adequacy. CONCLUSION: Appropriate treatment for CS-PA bacteremia initiated within the first 24 hours was associated with lower mortality, but this cannot be extrapolated for CR-PA.

Carbapenem-resistant Pseudomonas aeruginosa outbreak in an intensive care unit of a teaching hospital

The genetic similarity of carbapenem-resistant Pseudomonas aeruginosa strains isolated in the Hospital Universitário São Francisco, Bragança Paulista, São Paulo, Brasil, was evaluated by pulsed field gel electrophoresis (PFGE). A unique clone was detected among 5 of 7 isolates, suggesting that cross-contamination might have played a role in the spread of carbapenem-resistant P. aeruginosa strains. Interestingly, a similar PFGE pattern was encountered in a P. aeruginosa strain isolated from Hospital São Paulo that was used as a PFGE control.