Risk factors for treatment failure in patients receiving β-lactam/β-lactamase inhibitor combinations for Enterobacteriaceae bloodstream infection: A retrospective, single-centre, cohort study

Int J Antimicrob Agents. 2019 May;53(5):574-581. doi: 10.1016/j.ijantimicag.2019.01.005. Epub 2019 Jan 9.

Abstract

The aim of this study was to investigate risk factors for treatment failure in patients receiving in vitro-active therapy with β-lactam/β-lactamase inhibitor (BL/BLI) for Enterobacteriaceae bloodstream infection (E-BSI). This was a retrospective, single-centre study of patients diagnosed with E-BSI at an Italian centre over a 4-year period. Exclusion criteria were age <18 years, clinical data unavailable, polymicrobial BSI, failure to receive in vitro-active therapy and death within 72 h from drawing the index blood culture. Patients who received BL/BLI as appropriate empirical and/or definitive therapy for ≥50% of the total treatment duration were selected. The primary endpoint was all-cause 30-day mortality. The secondary endpoint was 90-day relapse. Of 1319 eligible patients, 835 were selected. A total of 714 received BL/BLI as appropriate empirical therapy, of whom 522 remained on BL/BLI as definitive therapy and 192 shifted to another antibiotic for <50% of the treatment duration; 121 received BL/BLI as definitive therapy only. Non-susceptibility to extended-spectrum cephalosporins (NS-ESCs) was detected in 207 episodes (24.8%). All-cause 30-day mortality was 6.8%. In multivariate analysis adjusted for NS-ESC, independent predictors of mortality were Charlson comorbidity index, septic shock, Proteus spp. and CVC-related BSI, whilst urinary source was a protective factor. The 90-day relapse rate was 4.2%. Immunosuppression was the main independent predictor for relapse. BL/BLI was the most common antibiotic administered to patients with E-BSI in this cohort. Among patients appropriately treated with BL/BLI, failure rates were low and were primarily associated with underlying diseases, clinical severity at BSI onset and infection source.

Keywords: All-cause 30-day mortality; Bloodstream infection; Enterobacteriaceae; Relapse; β-Lactam/β-lactamase inhibitor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / mortality
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / mortality
  • Female
  • Humans
  • Incidence
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Treatment Failure
  • Young Adult
  • beta-Lactamase Inhibitors / therapeutic use*
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • beta-Lactams