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Treatment of Staphylococcus aureus prosthetic joint infection in adults with retained hardware following debridement and completion of intravenous therapy: Oral antibiotic continuation therapy*¶

Treatment of Staphylococcus aureus prosthetic joint infection in adults with retained hardware following debridement and completion of intravenous therapy: Oral antibiotic continuation therapy*¶
Antibiotic regimen Dosing
Preferred regimens include:
One of the following:
Levofloxacin 500 to 750 mg daily
Ciprofloxacin 500 to 750 mg twice daily
plus
RifampinΔ 300 to 450 mg twice daily◊
Alternative regimens include:
One of the following agents:§
Trimethoprim-sulfamethoxazole 1 double-strength tablet twice daily
Doxycycline 100 mg twice daily
Minocycline 100 mg twice daily
Dicloxacillin 500 mg 3 or 4 times daily
Cefadroxil 500 mg twice daily
Cephalexin 500 mg 3 or 4 times daily
Flucloxacillin 500 mg 3 or 4 times daily
Fusidic acid (where available)¥ 500 mg 3 times daily
plus
RifampinΔ 300 to 450 mg twice daily◊
The doses recommended above are intended for adults with normal renal function; the doses of some of these agents must be adjusted in patients with renal insufficiency. Refer to the drug-specific monographs included within UpToDate for renal dose adjustments.

PJI: prosthetic joint infection.

* For patients with S. aureus PJI with retained hardware following debridement (eg, debridement and retention of prosthesis or 1-stage exchange), antibiotic therapy consists of pathogen-specific intravenous therapy in combination with rifampin for 2 to 6 weeks (refer to the UpToDate topic on treatment of PJI for further discussion). Thereafter, subsequent therapy for patients who undergo debridement and retention of hip, elbow, shoulder, or ankle PJI consists of pathogen-specific oral therapy in combination with rifampin to complete a total duration of 3 months. Subsequent therapy for patients who undergo debridement and retention of knee PJI consists of pathogen-specific oral therapy in combination with rifampin to complete a total duration of 6 months. Subsequent therapy for patients who undergo 1-stage exchange consists of pathogen-specific oral therapy in combination with rifampin to complete a total duration of 3 months.

¶ Following administration of antibiotic therapy as summarized in this table, indefinite antibiotic suppression with an oral regimen may be warranted in some patients; refer to the UpToDate topic on treatment of PJI for further discussion.

Δ Patients who cannot take rifampin because of drug resistance, allergy, toxicity, intolerance, or drug-drug interactions should remain on intravenous antistaphylococcal therapy for 4 to 6 weeks (before transitioning to antibiotic suppression with an oral regimen, if warranted).

◊ We favor administration of rifampin 450 orally twice daily; the dose may be reduced to 300 mg orally twice daily in the setting of nausea.

§ Alternative agents given with rifampin are recommended for patients who cannot take a fluoroquinolone due to allergies, intolerances, or resistance. If an alternative agent is used, confirm susceptibility.

¥ Not available in the United States. Fusidic acid should not be used alone; it must be combined with a second active agent to reduce the likelihood of selection for drug resistance. When rifampin is combined with fusidic acid, fusidic levels may be reduced.
Data from:
  1. Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013; 56:e1.
  2. Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015; 61:e26.
  3. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.
  4. Leijtens B, Elbers JB, Sturm PD, et al. Clindamycin-rifampin combination therapy for staphylococcal periprosthetic joint infections: a retrospective observational study. BMC Infect Dis 2017; 17:321.
  5. 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.
  6. Byren I, Bejon P, Atkins BL, et al. One hundred and twelve infected arthroplasties treated with 'DAIR' (debridement, antibiotics and implant retention): antibiotic duration and outcome. J Antimicrob Chemother 2009;63:1264.
  7. Berdal JE, Skråmm I, Mowinckel P, et al. Use of rifampicin and ciprofloxacin combination therapy after surgical debridement in the treatment of early manifestation prosthetic joint infections. Clin Microbiol Infect 2005; 11:843.
  8. Senneville E, Poissy J, Legout L, et al. Safety of prolonged high-dose levofloxacin therapy for bone infections. J Chemother 2007; 19:688.
  9. Soriano A, García S, Bori G, et al. Treatment of acute post-surgical infection of joint arthroplasty. Clin Microbiol Infect 2006; 12:930.
  10. Pushkin R, Iglesias-Ussel MD, Keedy K, et al. A randomized study evaluating oral fusidic acid (CEM-102) in combination with oral rifampin compared with standard-of-care antibiotics for treatment of prosthetic joint infections: A newly identified drug-drug interaction. Clin Infect Dis 2016; 63:1599.
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