Oral decontamination with aminoglycosides is associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant, KPC-producing Klebsiella pneumoniae

J Antimicrob Chemother. 2016 Nov;71(11):3242-3249. doi: 10.1093/jac/dkw272. Epub 2016 Jul 26.

Abstract

Objectives: Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients.

Methods: Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849).

Results: The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9).

Conclusions: Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Aminoglycosides / administration & dosage*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Carrier State / drug therapy
  • Colistin / pharmacology
  • Decontamination / methods*
  • Drug Resistance, Bacterial*
  • Female
  • Follow-Up Studies
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology*
  • Klebsiella Infections / mortality
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Middle Aged
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome
  • beta-Lactamases / metabolism*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • beta-Lactamases
  • Colistin

Associated data

  • ClinicalTrials.gov/NCT02604849