Antibiotics for treating chronic bone infection in adults

Osteomyelitis is an inflammation of the bone and bone marrow caused by pus-forming bacteria, mycobacteria or fungi. All bone infection that is long-standing is called chronic osteomyelitis. People with this condition are treated with systemic antibiotics, which can be given by mouth or parenterally (i.e. by injection into the muscle or vein). This review is an update of our previous 2009 publication.

We included eight small randomised trials involving 282 people. The trials presented results for a total of 248 people with chronic osteomyelitis. Post-traumatic bone infections were the most frequent type. Surgical removal of the infected tissue (debridement) before starting on antibiotic therapy was mentioned as part of treatment in all trials, but in four trials it was unclear whether all participants underwent surgery. There were five comparisons of different treatments but we could only pool results for the comparison of antibiotic given by mouth with antibiotic given parenterally.

The pooled results (which included data from 150 people) did not show any difference between people given antibiotics by mouth or parenterally in terms of the number of people who did not have symptoms (in 'remission') at the end of treatment (four trials) or 12 months later (or more) (three trials); nor in the number of people that had negative side effects or had a superinfection (another infection that is not sensitive to antibiotic treatment). This evidence suggests that the way antibiotics are given does not impact on the disease remission rate if the bacteria causing the infection are sensitive to the antibiotic used. However, confirmation is needed. There was either no or insufficient evidence on which to base judgements about the optimum length of antibiotic treatment or the best antibiotics to use.

Authors' conclusions: 

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.

Read the full 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.

Search strategy: 

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.

Selection criteria: 

Randomised controlled trials (RCTs) or quasi-RCTs addressing the effects of different antibiotic treatments given after surgical debridement for chronic osteomyelitis in adults.

Data collection and analysis: 

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.

Main results: 

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.