Oral Therapy: Other Agents

Although it should never be used alone for treating osteomyelitis, several reports have shown that rifampin improves treatment outcomes when used in combination with other antibiotics). Norden et al added rifampin to therapy with a β-lactam, doxycycline, or an aminoglycoside in 14 patients, most of whom had had osteomyelitis for >15 years and in whom multiple prior treatment attempts had failed. Overall, 50% were cured, and patients in whom treatment failed were all infected with gram-negative bacilli resistant to the nonrifampin agent. In another study of patients with S. aureus osteomyelitis, there were no relapses among 15 patients in whom rifampin was added to treatment with various other antibiotic agents compared with 5 relapses among 20 patients who did not receive adjunctive rifampin. Finally, adjunctive rifampin improved cure rates of prosthetic joint infections in 2 recent studies.

A large compassionate-use data set demonstrated that linezolid treatment cured 60% of the 89 patients with chronic osteomyelitis. In several case reports, clindamycin therapy successfully eradicated anaerobic osteomyelitis. Likewise, among 12 patients with chronic (primarily staphylococcal) osteomyelitis treated with clindamycin at very low doses (75–150 mg/6 h), 5 patients were cured and another 5 showed substantial improvement.

TMP-SMX is second only to ciprofloxacin in the number of published studies of its effectiveness for treatment of chronic osteomyelitis. Saengnipanthkul et al reported a 45% cure rate using standard dose TMP-SMX (1 double-strength tablet twice daily) to treat 66 patients with chronic osteomyelitis, only 55% of whom underwent surgical debridement. Cure rates based on surgical debridement were not separately reported. In contrast, Sanchez et al treated 27 patients with staphylococcal osteomyelitis (25 S. aureus) with a higher –than-usual dose of TMP-SMX (7 mg/kg/d of trimethoprim divided into 2 or 3 daily doses) along with rifampin for a mean of 5 weeks, in addition to surgical debridement. After follow-up of 6 months to 5 years, all of the patients were cured.

Javaloyas de Morlius et al reported their results with treating 37 patients with 44 episodes of osteomyelitis, 34 of which were associated with an orthopedic implant. After a week of parenteral antibiotic therapy, the patients received a median of 10 weeks of oral treatment with TMP-SMX plus rifampin (23 patients), TMP-SMX alone (5 patients), or rifampin plus ciprofloxacin (7 patients). At 2 years of follow-up, all 10 patients who had their hardware removed were cured, compared with 18 of 24 patients (75%) in whom hardware was left in place.

Stein et al prescribed TMP-SMX for 6–9 months to treat 39 patients with prosthetic devices infected with MRSA. The overall success rate was 67% in the intention-to-treat population and 87% in the per-protocol population (after exclusion of 9 patients who were unable to tolerate completing the treatment). Significantly more patients who had their infected prosthetics removed were cured compared with those who did not. Likewise, de Barros et al treated 60 patients with chronic osteomyelitis with TMP-SMX for 6 months, along with appropriate surgical debridement; 59 (98%) were cured after 12–60 months of follow-up. Finally, Nguyen et al reported that either TMP-SMX (8 mg/kg/d) or linezolid combined with rifampin cured 79%–89% of patients with infected orthopedic implants or chronic osteomyelitis. Taken together, these data support the efficacy of high-dose TMP-SMX, the importance of concurrent surgical debridement, and the possible benefit of adjunctive rifampin therapy and prolonged therapy when treating chronic osteomyelitis, especially in patients with an associated infected implant.

Consistent with their excellent bone penetration, both fosfomycin and fusidic acid, the latter preferably in combination with another anti-staphylococcal agent, have also demonstrated efficacy in treating chronic osteomyelitis. Others have summarized results of the numerous published case series describing fusidic acid combination therapy for osteomyelitis.