ROLE OF RIFAMPIN FOR TREATMENT OF ORTHOPEDIC IMPLANT-RELATED STAPHYLOCOCCAL INFECTIONS - A RANDOMIZED CONTROLLED TRIAL

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 t rial. Objective.-To evaluate the clinical efficacy of a rifampin combi nation 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 serv ices in tertiary care centers in collaboration with 5 orthopedic surge ons in Switzerland. Patients.-A total of 33 patients with culture-prov en 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 debridemen t and 2-week intravenous course of flucloxacillin or vancomycin with r ifampin or placebo, followed by either ciprofloxacin-rifampin or cipro floxacin-placebo long-term therapy. Main Outcome Measures.-Cure was de fined as (1) lack of clinical signs and symptoms of infection, (2) C-r eactive protein level less than 5 mg/L, and (3) absence of radiologica l signs of loosening or infection at the final follow-up visit at 24 m onths. Failure was defined as (1) persisting clinical and/or laborator y signs of infection or (2) persisting or new isolation of the initial microorganism. Results.-A total of 18 patients were allocated to cipr ofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combin ation. 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 ciprofl oxacin-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 rifa mpin combinations, and 5 of them were cured without removal of the dev ice. Conclusion.-Among patients with stable implants, short duration o f infection, and initial debridement, patients able to tolerate long-t erm (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.