Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group

JAMA. 1998 May 20;279(19):1537-41. doi: 10.1001/jama.279.19.1537.

Abstract

Context: Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial.

Objective: To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices.

Design: A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997.

Setting: Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland.

Patients: A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days).

Intervention: Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy.

Main outcome measures: Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism.

Results: A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device.

Conclusion: Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents / therapeutic use
  • Antibiotics, Antitubercular / therapeutic use*
  • Ciprofloxacin / therapeutic use
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Therapy, Combination / therapeutic use*
  • Female
  • Floxacillin / therapeutic use
  • Hip Prosthesis / adverse effects*
  • Humans
  • Knee Prosthesis / adverse effects*
  • Male
  • Middle Aged
  • Orthopedic Fixation Devices / adverse effects*
  • Penicillins / therapeutic use
  • Prosthesis-Related Infections / drug therapy*
  • Rifampin / therapeutic use*
  • Staphylococcal Infections / drug therapy*
  • Treatment Outcome
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antibiotics, Antitubercular
  • Penicillins
  • Floxacillin
  • Ciprofloxacin
  • Vancomycin
  • Rifampin