A Meta-Analysis of the Literature

The Effect of Withholding Antibiotics Prior to Bone Biopsy in Patients With Suspected Osteomyelitis

Peter Andrew Crisologo, DPM; Javier La Fontaine, DPM, MS; Dane K. Wukich, MD; Paul Kim, DPM, MS; Orhan K. Oz, MD, PhD; Lawrence A. Lavery, DPM, MPH


Wounds. 2019;31(8):205-212. 

In This Article

Abstract and Introduction


Objective: The aim of this meta-analysis is to evaluate the effect of withholding antibiotics prior to obtaining a bone biopsy in the diagnosis of osteomyelitis.

Methods: Literature searches on Scopus, PubMed, and Google Scholar were performed with the input antibiotic, bone, biopsy, osteomyelitis, and prior both separately and together, though initially as a combination, as key words for all study types in the English language published up until July 2018. The initial combination search (and subsequent additional search of the references) yielded 924 related articles, which ultimately resulted in 12 articles with adequate data for analysis. Data were analyzed using an inverse variance method to determine the weight of the studies in a random effects model, pooling the data for odds ratios (OR) and heterogeneity. Bias risk was determined with the Quality Assessment of Diagnostic Accuracy Studies 2 system.

Results: Of the 12 studies, 8 failed to demonstrate that antibiotics administered prior to bone biopsy have an effect on culture yield, while 4 reported a significant effect on culture yield. The total weighted OR for all studies was 2.02 (95% confidence interval [CI], 0.94–4.36; P = .04) and the prediction interval was 0.17–23.63. When vertebral osteomyelitis (VO) and nonvertebral osteomyelitis (NVO) articles were evaluated separately, the VO OR was 2.95 (95% CI, 1.40–6.24) and the prediction interval was 0.40–21.53. The OR for NVO was 0.66 (95% CI, 0.04–12.03) and the prediction interval was 0–114.53.

Conclusions: When all studies as well as when NVO studies only were evaluated, there was no significant difference in bacterial pathogen yield based on antibiotic exposure. When VO studies were evaluated separately, there were fewer pathogens recovered than when antibiotics were administered prior to obtaining bone cultures.


There is a strong belief that antibiotics should be held prior to bone culture. This theory stems from the thought that prebiopsy antibiotics will penetrate into the bone and interfere with bacterial pathogen recovery and identification with traditional cultures; however, the results of current publications are inconsistent regarding whether this theory should be supported or rejected.[1–12] If antibiotics are unnecessarily withheld, especially in cases of adjacent abscess, compromised host, or open wound, the delay could result in sepsis, bacteremia, and worse clinical outcomes.

Most of the published work in this area are from patients with hematogenous vertebral osteomyelitis (VO). The theory that holding antibiotics is necessary to obtain "true" culture results has been generalized to other types of contiguous osteomyelitis such as diabetic foot, pressure ulcer, and trauma.[13] While the disease is similar in that it is an infection of the bone, there are several differences in the overall disease pathology: etiology (hematogenous spread vs. contiguous spread), patient demographics, risk factors, comorbidities, time to presentation, concomitant soft tissue necrosis and abscess, clinical outcomes, and treatment protocols. With multiple types of osteomyelitis, it begs the question if one type of osteomyelitis can be generalizable to other types.

Several practice guidelines[13–17] recommend stopping antibiotics before bone cultures are obtained but recognize the strength of the literature to support this recommendation is low or does not comment on holding antibiotics.[18] Some recommend withholding antibiotics, even when the results of the study were negative.[7,9,19] Others note the time period recommended to withhold antibiotics is arbitrary[6] and the time recommended to hold antibiotics ranges from several days to weeks.[13–15,20] In contrast, the orthopedic literature endorses administration of empirical antibiotics in trauma situations with the understanding that intraoperative biopsy of the bone will be used to target the antibiotics to the infecting pathogens.[21–23] The present authors have been unable to identify any literature that has evidence to support withholding antibiotics in diabetic foot infections, trauma, pressure ulcers, or other causes of direct extension osteomyelitis. The aim of this study is to evaluate the current literature to determine if sufficient evidence is present to recommend withholding prebiopsy antibiotics as a step to increase traditional culture success.