PHARMACOLOGY OF OSTEOMYELITIS THERAPY

Abstract

The standard recommendation for treating chronic osteomyelitis is 6 weeks of parenteral antibiotic therapy. However, oral antibiotics are available that achieve adequate levels in bone, and there are now more published studies of oral than parenteral antibiotic therapy for patients with chronic osteomyelitis. Oral and parenteral therapies achieve similar cure rates; however, oral therapy avoids risks associated with intravenous catheters and is generally less expensive, making it a reasonable choice for osteomyelitis caused by susceptible organisms. Addition of adjunctive rifampin to other antibiotics may improve cure rates. The optimal duration of therapy for chronic osteomyelitis remains uncertain. There is no evidence that antibiotic therapy for >4–6 weeks improves outcomes compared with shorter regimens. In view of concerns about encouraging antibiotic resistance to unnecessarily prolonged treatment, defining the optimal route and duration of antibiotic therapy and the role of surgical debridement in treating chronic osteomyelitis are important, unmet needs.

Chronic osteomyelitis is an infection of bone that does not result from acute hematogenous seeding or penetrating injury and usually occurs by contiguous spread and has been present for several weeks. Perhaps the earliest known case of chronic osteomyelitis dates to the Permian era, in an unfortunate dimetrodon that developed infection in a fractured spinal shaft. This 250 million–year-old case highlights 3 of the problems that remain common when managing chronic osteomyelitis: (1) the diagnosis was established only after bone (or rather fossil) biopsy; (2) no cultures were performed to define the etiologic organism; and (3) treatment (if any) was probably delayed and certainly ineffective.

In the antibiotic era, chronic osteomyelitis remains difficult to treat and has a high rate of relapse after apparently successful treatment. Indeed, case reports have described relapses of osteomyelitis up to 80 years after the initial presentation. These relapses are probably due to bacterial evasion of host defenses by hiding intracellularly and as nonreplicating persisters within biofilm. Because of these concerns, clinicians often treat chronic osteomyelitis with antibiotic therapy that is parenteral, high dose, and prolonged. This standard recommendation derives largely from the belief that it takes 3–4 weeks for infected bone to revascularize as well as from experience treating children with acute osteomyelitis. It was codified by a seminal case series by Waldvogel et al in 1970. The authors stated that “osteomyelitis is rarely controlled without the combination of careful, complete surgical debridement and prolonged (4–6 weeks) parenteral antibiotic therapy at high dosage.” However, this case series was retrospective and uncontrolled, and it included a heterogeneous patient population, and parenteral penicillin was the predominant antibiotic administered.

What have we learned about treating chronic osteomyelitis in the past few decades? Previous reviews of this topic have concluded that available literature is inadequate to determine the best agent, route, or duration of antibiotic therapy. Undeterred, we set out to review studies published since 1970 in an attempt to address 4 fundamental questions regarding treatment of chronic osteomyelitis in adults: (1) Are certain antibiotic agents preferred choices? (2) Are oral regimens acceptable for selected cases? (3) For how long should antibiotic therapy be given? and (4) Is surgical debridement always necessary for cure? We searched PubMed and ScienceDirect for the term “osteomyelitis” from 1970 to 2011, and EBSCO, Web of Science, and Google Scholar for any types of studies on treatment of chronic osteomyelitis in adults. We reviewed all articles if they, or at least their abstracts, were in English.

PHARMACOLOGY OF OSTEOMYELITIS THERAPY