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

• Published in: BMC infectious diseases Vol. 19; no. 1; pp. 830 - 13
• Main Authors: Cienfuegos-Gallet, Astrid V., Ocampo de Los Ríos, Ana M., Sierra Viana, Patricia, Ramirez Brinez, Faiver, Restrepo Castro, Carlos, Roncancio Villamil, Gustavo, del Corral Londoño, Helena, Jiménez, J. Natalia
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.10.2019; BioMed Central Ltd; BMC
• Subjects: Aged; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; Bacterial and fungal diseases; Carbapenem resistance; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Case-Control Studies; Case-control study; Cefepime; Cefepime - adverse effects; Cefepime - therapeutic use; Ciprofloxacin; Ciprofloxacin - adverse effects; Ciprofloxacin - therapeutic use; Cohort analysis; Cohort study; Colombia; Control methods; Drug resistance; Drug Resistance, Multiple, Bacterial; Drug therapy; Endemic Diseases; Epidemiology; Factor analysis; Failure analysis; Failure times; Female; Genotype; Hospitals; Humans; Infections; Infectious Diseases; innapropriate therapy; Internal Medicine; Kaplan-Meier Estimate; Klebsiella; Klebsiella Infections - drug therapy; Klebsiella Infections - mortality; Klebsiella pneumoniae; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - isolation & purification; Laboratories; length of antibiotic use; Logistic Models; Male; Medical equipment; Medical instruments; Medical Microbiology; Medical research; Medicine; Medicine & Public Health; Meropenem; Meropenem - adverse effects; Meropenem - therapeutic use; Microbial drug resistance; Middle Aged; Mortality; Parasitology; Pathogenic microorganisms; Patient outcomes; Patients; Phenotype; Pneumonia; Population; Prospective Studies; Regression analysis; Regression models; Research Article; Resistance factors; Risk analysis; Risk Factors; Studies; Surveillance; Survival; Survival Analysis; Therapy; Tropical Medicine; Urinary Catheters - adverse effects; Colombia; risk factors; length of antibiotic use; Cohort study; innapropriate therapy; mortality; Case-control study; Carbapenem resistance; Klebsiella pneumoniae
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-019-4461-x

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.