Low-dose Gentamicin for Uncomplicated Enterococcus faecalis Bacteremia May be Nephrotoxic in Children

Clin Infect Dis. 2015 Oct 1;61(7):1119-24. doi: 10.1093/cid/civ461. Epub 2015 Jun 16.

Abstract

Background: Uncertainty exists regarding the role of synergistic gentamicin for uncomplicated Enterococcus faecalis bacteremia in children.

Methods: We conducted a retrospective, observational study comparing clinical outcomes of children with E. faecalis bacteremia without endocarditis receiving ampicillin monotherapy with those receiving ampicillin along with low-dose gentamicin therapy. To account for nonrandom assignment of combination therapy, propensity score weighting was combined with multivariable regression to estimate the effect of combination therapy on duration of bacteremia, bacteremic relapse, and acute kidney injury (AKI).

Results: One hundred sixty-three (52%) patients received ampicillin with low-dose gentamicin, and 150 (48%) patients received ampicillin monotherapy. Incorporating propensity-score weighting with additional adjustment for source control measures, patients receiving combination therapy experienced bacterial clearance 10 hours faster than children receiving ampicillin monotherapy (adjusted mean difference 0.42; confidence interval (CI), .02 to .82; P = .04). Bacteremic relapse was similar between the two groups (17% vs 18%); adjusted hazards ratio (aHR) 1.12; 95% CI, .65 to 1.92. Children receiving low-dose gentamicin had approximately twice the risk of developing AKI compared to children not receiving this agent, adjusting for the receipt of additional nephrotoxins (aHR 1.94; 95% CI, 1.48-2.97).

Conclusions: Our study suggests that for children with uncomplicated E. faecalis bacteremia, the addition of low-dose gentamicin may decrease the time to bacterial clearance by 10 hours but without any impact on recurrent bacteremia. However, with this potential benefit comes the increased likelihood of AKI. Low-dose gentamicin for the treatment of uncomplicated enterococcal bacteremia may pose harm to children with limited benefit.

Keywords: Enterococcus faecalis; aminoglycosides; gentamicin; pediatrics; synergy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / epidemiology
  • Adolescent
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia / drug therapy*
  • Bacteremia / epidemiology
  • Bacteremia / microbiology
  • Baltimore / epidemiology
  • Child
  • Child, Preschool
  • Enterococcus faecalis*
  • Gentamicins / administration & dosage
  • Gentamicins / adverse effects*
  • Gentamicins / therapeutic use
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / epidemiology
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Infant
  • Retrospective Studies
  • Risk

Substances

  • Anti-Bacterial Agents
  • Gentamicins