Rifampin and Prosthetic Joint Infections
By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: In patients with prosthetic joint infection, no modifiable surgical or antibiotic factors were independently associated with success or failure. Factors not associated with outcomes include the extent of debridement, exchange of mobile parts, use of rifampin or of ciprofloxacin, and duration of intravenous or oral antibiotic administration.
SOURCE: Davis JS, Metcalf S, Clark B, et al. Predictors of treatment success after periprosthetic joint infection: 24-month follow up from a multicenter prospective observational cohort study of 653 patients. Open Forum Infect Dis 2022;9:ofac048.
The Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) study initially described 783 patients and found that late acute infection, likely the result of hematogenous seeding, was most common and that management was highly heterogeneous.1 Davis and colleagues reported an analysis of modifiable variables in medical and surgical management in the 653 patients for whom 24-month data was available. Of these, 549 (84%) were alive and infection-free, with 449 (69%) meeting criteria for clinical cure (no evidence of infection, not requiring antibiotic) and 350 (54%) meeting criteria for treatment success (clinically cured with retained prosthesis).
Host factors associated with treatment success included younger age, the hip as the index joint, early infection (< 30 days post-implant), higher serum albumin, and absence of malignancy or chronic renal disease. The success rate was 60% for hips and 48% for knees (P < 0.001). Success with infections resulting from Staphylococcus aureus, Cutibacterium spp., or gram-negative bacilli were each only 46%, while success occurred in 56% to 58% of those caused by other pathogens and in 71% of culture-negative cases.
Treatment of early infection was successful in 74%, while this was true in only 44% of late-acute infections (< 30 days, < 7 days of symptoms, no sinus tract). Among the late infections, two-stage procedures provided success rates similar to those observed in early infections (72% vs. 79%), while after DAIR (debridement, antibiotics, implant retention), the success rate was only 48%.
Among patients who underwent DAIR, success was achieved in 80% of those who presented within 30 days of implant, but the rate decreased progressively thereafter, falling to 45% after one year — and this was independent of the duration of symptoms. DAIR in patients with late-acute prosthetic joint infection (PJI) had poor results, suggesting that revision arthroplasty is the preferred approach in these patients. Among the 170 episodes with two-stage procedures, 129 (76%) had clinical cure and 110 (65%) experienced treatment success.
In the 352 patients of the total cohort who underwent DAIR, baseline factors independently associated with treatment success were early infection, a shorter duration of infection symptoms, and higher serum albumin concentration, while the presence of comorbidity and of S. aureus infection each were associated with failure. None of the examined modifiable surgical or antibiotic factors, including the extent of debridement, exchange of mobile parts, use of rifampin or of ciprofloxacin, or duration of intravenous or oral antibiotic administration, were independently associated with success or failure.
Overall, adjunctive rifampin was administered during 255 episodes, including 176/352 (51%) of those with DAIR, 154/254 (61%) with a gram-positive infection, and 143/192 (75%) when Staphylococcus was recovered. Among the 255, at least one adverse reaction attributed to rifampin occurred in 68 patients (26%), leading to its discontinuation in 36 patients (14.1%). Rifampin use was not associated with a statistically significant difference in treatment success overall, in patients with gram-positive infection, in those with Staphylococcus infection, or even in those with Staphylococcus infection who received the drug for at least 14 days.
The use of rifampin in PJI is recommended by many, but the supportive evidence is, at best, weak. A recent meta-analysis concluded that “rifampicin may only prevent a small fraction of all treatment failures.”2 On the other hand, a multicenter observational study found apparent benefit to the use of adjunctive rifampin.3
To my knowledge, only a single randomized trial of its use is available, and a careful reexamination of this study is warranted.4 The trial randomized a total of 33 patients who underwent debridement, 15 of whom had PJI while 18 had infection of osteosynthesis devices. Only a total of 24 patients (12 in each arm) completed the study. After two weeks of intravenous flucloxacillin or vancomycin together with either rifampin or placebo, treatment was changed to orally administered ciprofloxacin with or without placebo. Thus, although outcomes favored combination therapy, the small sample size and inclusion of devices other than prosthetic joints make interpretation of the results fraught — as does the use of a fluoroquinolone (ciprofloxacin), which is significantly less potent against S. aureus than, e.g., levofloxacin.5
The only conclusion that one can reach after reviewing all of these data is that there is a great need for a large multicenter randomized clinical trial designed to finally determine the role, if any, of adjunctive rifampin in the treatment of PJI.
- Manning L, Metcalf S, Clark B, et al. Clinical characteristics, etiology, and initial management strategy of newly diagnosed periprosthetic joint infection: A multicenter, prospective observational cohort study of 783 patients. Open Forum Infect Dis 2020;7:ofaa068.
- Scheper H, Gerritsen LM, Pijls BG, et al. Outcome of debridement, antibiotics, and implant retention for staphylococcal hip and knee prosthetic joint infections, focused on rifampicin use: A systematic review and meta-analysis. Open Forum Infect Dis 2021;8:ofab298.
- Beldman M, Löwik C, Soriano A, et al. If, when, and how to use rifampin in acute staphylococcal periprosthetic joint infections, a multicentre observational study. Clin Infect Dis 2021;73:1634-1641.
- Zimmerli W, Widmer AF, Blatter M, et al. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: A randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 1998;279:1537-1541.
- Kang SL, Rybak MJ, McGrath BJ, et al. Pharmacodynamics of levofloxacin, ofloxacin, and ciprofloxacin, alone and in combination with rifampin, against methicillin-susceptible and -resistant Staphylococcus aureus in an in vitro infection model. Antimicrob Agents Chemother 1994;38:2702-2709.
In patients with prosthetic joint infection, no modifiable surgical or antibiotic factors were independently associated with success or failure. Factors not associated with outcomes include the extent of debridement, exchange of mobile parts, use of rifampin or of ciprofloxacin, and duration of intravenous or oral antibiotic administration.
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