Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment

Abstract

Bloodstream infections (BSIs) caused by Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-KP) are associated with high mortality rates. We investigated outcomes, risk factors for mortality and impact of appropriate antimicrobial treatment in patients with BSIs caused by molecularly confirmed KPC-KP. All consecutive patients with KPC-KP BSIs between May 2008 and May 2010 were included in the study and followed-up until their discharge or death. Potential risk factors for infection mortality were examined by a case-control study. Case-patients were those who died from the BSI and control-patients those who survived. Appropriate antimicrobial therapy was defined as treatment with in vitro active antimicrobials for at least 48 h. A total of 53 patients were identified. Overall mortality was 52.8% and infection mortality was 34%. Appropriate antimicrobial therapy was administered to 35 patients; mortality due to infection occurred in 20%. All 20 patients that received combination schemes had favourable infection outcome; in contrast, seven of 15 patients given appropriate monotherapy died (p 0.001). In univariate analysis, risk factors for mortality were age (p <0.001), APACHE II score at admission and infection onset (p <0.001) and severe sepsis (p <0.001), while appropriate antimicrobial treatment (p 0.003), combinations of active antimicrobials (p 0.001), catheter-related bacteraemia (p 0.04), prior surgery (p 0.014) and other therapeutic interventions (p 0.015) were significantly associated with survival. Independent predictors of mortality were age, APACHE II score at infection onset and inappropriate antimicrobial treatment. Among them, appropriate treatment is the only modifiable independent predictor of infection outcome.

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

“…46 Poor outcomes are also due to treatment with ineffective, empiric antibiotics before carbapenem resistance is identified by the laboratory. 47,48 In one study of neutropenic patients with CRE bloodstream infections, nearly 90% of patients were started on ineffective therapy at presentation and a median of 55 hours elapsed between time of culture collection and administration of effective antibiotic therapy. 45 Because mortality from sepsis increases 7.6% for every hour's delay in effective antibiotic administration, 49 diagnostics that speed up detection and appropriate treatment of CRE by even a few hours should improve outcomes of patients with invasive CRE infections.…”

“…48,[52][53][54] This remains controversial as not all studies found a survival advantage among patients with CRE infections who received combination therapy vs. monotherapy and results of ongoing randomized studies are not yet available. 55 There is some evidence that non-colistin based regimens had worse outcomes than colistin-based regimens.…”

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates from a university hospital in Brazil

“…The most common carbapenemases in K. pneumoniae are the K. pneumoniae carbapenemases (KPC) [6]. KPC-associated infections are predominantly nosocomial, involving patients with multiple risk factors, and the mortality rates can be high [7].…”

Bloodstream infections in the Intensive Care Unit

“…[89][90] For the treatment of BSIs sustained by KPC-producing Enterobacteriacae, which are the most common carbapenem-resistant nosocomial isolate, combination regimens including at least 2 active drugs have been associated with improved clinical outcomes and reduced mortality in comparison with the use of only one active drug, in particular when the combination includes a carbapenem. 45,[91][92] Tumbarello et al analyzed a cohort of 125 patients with KPC-K. pneumoniae-BSIs and reported a significantly lower 30-day mortality in patients receiving a combination regimen compared with the ones treated with a monotherapy (34,1% vs 54,3%, P D 0,02). In particular, multivariate analysis found that a targeted therapy with meropenem in combination with colistin and tigecycline was independently associated with reduced mortality (OR:0.11; 95%CI: .02-.69; P D 0.01).…”