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

Abstract

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.

Mortality-related factors in patients with OXA-48 carbapenemase-producing Klebsiella pneumoniae bacteremia

“…[ 11 , 27 , 35 , 38 ] A recent study showed an increased risk of acquiring a CRKp infection for each day meropenem (OR 1.18), cefepime (OR 1.22), and ciprofloxacin (OR 2.37) were administered. [ 39 ] As with other studies, [ 14 , 28 , 29 ] we found a greater likelihood of bacteremia due to CRKp in those patients admitted to a ward with a CRKp outbreak, which could be related to several factors include greater patient fragility (immunosuppression, greater comorbidity), higher use of antibiotics, and invasive procedures. [ 27 , 40 , 41 ] We also found an increased risk of CRKp bacteremia in patients with a hospital stay exceeding 20 days during the previous year.…”

Prevalence of pathogenic Klebsiella pneumoniae based on PCR capsular typing harbouring carbapenemases encoding genes in Uganda tertiary hospitals

“…Findings from this study exhibited that 56.4% of the MDR K. pneumoniae isolates were recovered from urine, 21.2% from pus swab and 10.1% from blood. Indeed, previous studies implicated K. pneumoniae as one of the predominant causes of urinary tract infections, surgical wound infections and bacteriemia [ 21 , 22 ].…”

“…Furthermore, out of the 106 klebsiella pneumoniae capsular types, 37 exhibited resistance to carbapenems yet carbapenems are regarded as the drugs of choice for treatment of MDR Gram-Negative HAI when the first line drugs have failed [ 47 ]. Acquisition of carbapenem resistance in pathogenic bacteria correlates with treatment failure in addition to increased morbidity and mortality [ 21 ]. Investigations elsewhere which looked clinical samples, associated coexistence of capsular and other virulent factors such as rmpA and aerobactin genes with hypervirulent or hypermucoviscous K. pneumoniae variant (hvKP) [ 48 , 49 ].…”

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

“…Timely and appropriate antimicrobial therapy is critically important for treatment of patients with BSI [13,14]. Recent studies highlighted that inappropriate empiric treatment is associated with poor outcome of patients with urinary tract [15] or any type of infection due to KPC-Kp [16,17]. Among non-neutropenic patients with BSI due to KPC-Kp, Satlin et al did not find any association between timing of active therapy and mortality, but a trend to higher mortality rates was observed in patients who did not receive active therapy within the first 12 h from BSI onset [18]; however, the majority of patients (84%) acquired infection in the community or in non-ICU wards [18].…”