Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival

Abstract

Background: Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes.

Methods: The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted.

Results: Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014).

Conclusion: Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.

Keywords: Blood stream infection; Carbapenemase; Enterobacteriaceae; OXA-48; Survival; Treatment.