Rifampin and the Treatment of Orthopedic Implant Infection
July 1, 1998 4 minutes read
Rifampin and the Treatment of Orthopedic Implant Infection
ABSTRACT & COMMENTARY
Synopsis: For treatment of orthopedic implant-associated staphylococcal infections, addition of rifampin to standard antimicrobial therapy may improve the chance of success, and may permit salvage of the prosthesis.
Source: Zimmerli W, et al. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: A randomized controlled trial. JAMA 1998;279:1537-1541.
Osteoarticular infections involving orthopedic implants, either internal fixation devices or total joint prostheses, are especially difficult to treat. The presence of infection is sometimes difficult to recognize, the infecting microorganisms are often resistant to many commonly used antimicrobial agents, and surgical treatment typically is necessary. Removal of the implanted material is often required before infection can be eradicated. Generally, intravenous antibiotics are administered for prolonged periods (often a minimum of 4-6 weeks) at considerable logistic and economic cost.
Zimmerli and associates in Switzerland prospectively compared the effects of treating implant-related staphylococcal infection with or without rifampin-containing regimens. Patients were eligible for study if they had documented Staphylococcus aureus or coagulase-negative staphylococcal infection, symptoms of infection for less than one year (in fact, most were symptomatic for less than 1 week, and none for more than 3 weeks), and a stable implant. In all, 33 patients were enrolled; all but four patients underwent thorough surgical debridement at study entry. Implants were not removed.
Treatment comprised an initial two-week course of intravenous flucloxacillin (in 26 of the 33 patients) or vancomycin (in those with a methicillin-resistant pathogen or in patients with penicillin allergy). Half of the patients also received oral rifampin 450 mg q12h; while the other half received a matching placebo. Following completion of the intravenous regimen, oral ciprofloxacin 750 mg twice daily was given to all patients for three months (6 months in the case of those with knee prosthesis infection); rifampin or placebo was continued throughout this oral treatment phase as well. Patients were monitored for two years.
Patients were fairly evenly matched. Most had S. aureus infections (none of these was methicillin-resistant); slightly more than half of the patients had internal fixation device-related infection. Approximately half of the patients' infections occurred within two months of orthopedic hardware implantation.
The results of the study were dramatic. Of those who completed protocol, all 12 in the rifampin-treated cohort were cured (defined as absence of signs and symptoms of infection, absence of radiographic evidence of infection, and absence of the initially infecting pathogen in those patients whose internal fixation device was removed after completion of therapy); only 58% (7 of 12) in the rifampin-spared group were cured (P = 0.02). Nine patients were dropped from the study due to compliance factors or adverse reactions such as nausea or rash; several were able to resume therapy with dose modification. On an intention-to-treat analysis, those randomized to the rifampin-containing arm tended to fare better (89% vs 60% cure rate) (P = 0.10).
Zimmerli et al conclude that orthopedic implant-related infections caused by rifampin- and ciprofloxacin-susceptible S. aureus and coagulase-negative staphylococci can be cured with a rifampin-containing regimen if a series of conditions is met: the implant is stable, treatment is begun promptly after symptoms of infection first appear, and thorough debridement and drainage can be performed.
COMMENT BY JERRY D. SMILACK, MD
This study raises more questions than it answers. Initial reading suggests clear superiority of a rifampin-containing antimicrobial combination over monotherapy in the treatment of orthopedic-device associated infections. Bear in mind, however, that the patients participating in this study were highly selected. All had acute infection, with symptoms usually present for less than one week. In the real world, I suspect most patients referred to infectious disease consultants have symptoms of infection for considerably longer periods of time. Most patients' infections in this study occurred within two months of the initial surgical procedure or followed presumed acute hematogenous seeding of the implant sometime later. Again, in the practices of many infectious disease physicians, these conditions pertain infrequently. The Swiss study was skewed toward patients with infected internal fixation devices; fewer than half (only 15 of the total of 33 patients) had an infected hip or knee prosthesis.
The microbiology of infections in this study was also narrowly limited. Only patients with S. aureus or coagulase-negative staphylococcal infections were enrolled. While staphylococci clearly predominate in orthopedic device-related infection, a substantial number of infections due to propionibacteria, enterobacteriaceae, pseudomonads, and candida occur. Results from this study clearly cannot be extrapolated to patients with non-staphylococcal infections. It is important to note that all S. aureus isolates, and most coagulase-negative isolates, in this study were methicillin-susceptible. In my practice, approximately 25% of S. aureus strains and nearly all coagulase-negative isolates are methicillin-resistant. These local factors must be weighed when trying to interpret the Swiss study.
Finally, Zimmerli et al's treatment regimen differs considerably from that commonly used in the United States, where typically a 4-6 week course of intravenous therapy is administered. Certainly their two week intravenous and then 3-6 month oral regimen is an attractive option, but adopting it without the benefit of experience in larger groups of patients might be premature.
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