Conterno Lucieni O, Turchi Marilia D
Department of General Internal Medicine and Clinical Epidemiology Unit, Marilia Medical School, Avenida Monte Carmelo 800, Fragata, Marilia, São Paulo, Brazil, 17519-030.
Cochrane Database Syst Rev. 2013 Sep 6;2013(9):CD004439. doi: 10.1002/14651858.CD004439.pub3.
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.
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.
慢性骨髓炎一般采用抗生素和外科清创术进行治疗，但可能会间歇性持续数年，且经常治疗失败或复发。尽管抗生素和外科治疗都取得了进展，但长期复发率仍在20%左右。这是对2009年首次发表的Cochrane系统评价的更新。
确定不同全身抗生素治疗方案对成人慢性骨髓炎的疗效。
我们检索了Cochrane骨、关节和肌肉创伤组专业注册库（2012年10月）、Cochrane对照试验中央注册库（Cochrane图书馆2012年第9期）、MEDLINE（1948年1月至2012年9月第4周）、EMBASE（1980年1月至2012年第40周）、LILACS（2012年10月）、世界卫生组织国际临床试验注册平台（2012年6月）以及相关文章的参考文献列表。
针对外科清创术后给予不同抗生素治疗对成人慢性骨髓炎疗效的随机对照试验（RCT）或半随机对照试验。
两位综述作者独立筛选纳入的论文，提取数据并评估纳入试验的偏倚风险。在适当情况下，我们使用固定效应模型合并数据。
我们纳入了八项小型试验，共282例慢性骨髓炎患者。248例患者有可用数据。大多数患者为男性，患有创伤后骨髓炎，受累部位通常为胫骨和股骨（如有记录）。各试验的抗生素方案、治疗持续时间和随访情况各不相同。所有试验均提到在开始抗生素治疗前进行外科清创术作为治疗的一部分，但四项试验中不清楚所有参与者是否都接受了外科清创术。我们发现研究质量和报告情况往往不足。特别是，由于未采用随机分配隐藏和随访不充分，我们判定几乎所有试验都存在中度至高度偏倚风险。四项试验比较了抗生素的口服给药与胃肠外给药途径。两组在治疗结束时的缓解率无统计学显著差异（70/80与58/70；风险比（RR）1.04，95%置信区间（CI）0.92至1.18；四项试验，150例参与者）。两组在治疗12个月或更长时间后的缓解率无统计学显著差异（49/64与44/54；RR 0.94，95%CI 0.78至1.13；三项试验，118例参与者）。两组在轻度不良事件的发生方面也无显著差异（11/64与8/54；RR 1.08，95%CI 0.49至2.42；三项试验，118例参与者）或中度和重度不良事件（3/49与4/42；RR 0.69，95%CI 0.19至2.57；三项试验，91例参与者）。两组参与者均发生了二重感染（口服组5/66，胃肠外给药组4/58；RR 1.08，95%CI 0.33至3.60；三项试验，124例参与者）。参与者较少的单项试验在以下四项比较中未发现缓解或不良事件方面的统计学显著差异：仅口服与胃肠外给药加口服；胃肠外给药加口服与仅胃肠外给药；两种不同的胃肠外抗生素方案；以及两种不同的口服抗生素方案。没有试验比较慢性骨髓炎不同抗生素治疗持续时间，或针对细菌种类或疾病严重程度调整缓解率。
有限且质量低的证据表明，如果细菌对所用抗生素敏感，抗生素给药途径（口服与胃肠外给药）不影响疾病缓解率。然而，这一点以及不良反应方面缺乏统计学显著差异均需进一步证实。对于慢性骨髓炎抗生素治疗的其他方面，没有证据或证据不足。大多数纳入试验是在20多年前进行的，而目前我们面临着对许多现有用于医疗保健的抗生素耐药的细菌患病率高得多的情况。这种不断演变的细菌耐药性是治疗慢性骨髓炎选择抗生素时的另一项挑战。
