Title:
Antibiotics for treating chronic osteomyelitis in adults.

Abstract:
Chronic osteomyelitis is generally treated with antibiotics and surgical debridement but can persist intermittently for years with frequent therapeutic failure or relapse. Despite advances in both antibiotic and surgical treatment, the long-term recurrence rate remains around 20%. This is an update of a Cochrane review first published in 2009.
To determine the effects of different systemic antibiotic treatment regimens for treating chronic osteomyelitis in adults.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (October 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 9), MEDLINE (January 1948 to September Week 4 2012), EMBASE (January 1980 to 2012 Week 40), LILACS (October 2012), the WHO International Clinical Trials Registry Platform (June 2012) and reference lists of relevant articles.
Randomised controlled trials (RCTs) or quasi-RCTs addressing the effects of different antibiotic treatments given after surgical debridement for chronic osteomyelitis in adults.
Two review authors independently screened papers for inclusion, extracted data and appraised risk of bias in the included trials. Where appropriate, we pooled data using the fixed-effect model.
We included eight small trials involving a total of 282 participants with chronic osteomyelitis. Data were available from 248 participants. Most participants were male with post-traumatic osteomyelitis, usually affecting the tibia and femur, where recorded. The antibiotic regimens, duration of treatment and follow-up varied between trials. All trials mentioned surgical debridement before starting on antibiotic therapy as part of treatment, but it was unclear in four trials whether all participants underwent surgical debridement.We found that study quality and reporting were often inadequate. In particular, we judged almost all trials to be at moderate to high risk of bias due to failure to conceal allocation and inadequate follow-up.Four trials compared oral versus parenteral route for administration of antibiotics. There was no statistically significant difference between the two groups in the remission at the end of treatment (70/80 versus 58/70; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.92 to 1.18; four trials, 150 participants). There was no statistically significant difference between the two groups in the remission rate 12 or more months after treatment (49/64 versus 44/54; RR 0.94, 95% CI 0.78 to 1.13; three trials, 118 participants). There was also no significant difference between the two groups in the occurrence of mild adverse events (11/64 versus 8/54; RR 1.08, 95% CI 0.49 to 2.42; three trials, 118 participants) or moderate and severe adverse events (3/49 versus 4/42; RR 0.69, 95% CI 0.19 to 2.57; three trials, 91 participants). Superinfection occurred in participants of both groups (5/66 in the oral group versus 4/58 in the parenteral group; RR 1.08, 95% CI 0.33 to 3.60; three trials, 124 participants).Single trials with few participants found no statistical significant differences for remission or adverse events for the following four comparisons: oral only versus parenteral plus oral administration; parenteral plus oral versus parenteral only administration; two different parenteral antibiotic regimens; and two different oral antibiotic regimens. No trials compared different durations of antibiotic treatment for chronic osteomyelitis, or adjusted the remission rate for bacteria species or severity of disease.
Limited and low quality evidence suggests that the route of antibiotic administration (oral versus parenteral) does not affect the rate of disease remission if the bacteria are susceptible to the antibiotic used. However, this and the lack of statistically significant differences in adverse effects need confirmation. No or insufficient evidence exists for other aspects of antibiotic therapy for chronic osteomyelitis.The majority of the included trials were conducted over 20 years ago and currently we are faced with a far higher prevalence of bacteria that are resistant to many of the available antibiotics used for healthcare. This continuously evolving bacterial resistance represents another challenge in the choice of antibiotics for treating chronic osteomyelitis.