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Is Bone Loss or Devascularization Associated With Recurrence of Osteomyelitis in Wartime Open Tibia Fractures?

Petfield, Joseph L., MD; Tribble, David R., MD, DrPH; Potter, Benjamin K., MD; Lewandowski, Louis R., MD; Weintrob, Amy C., MD; Krauss, Margot, MD, MPH; Murray, Clinton K., MD; Stinner, Daniel J., MD Trauma Infectious Disease Outcomes Study Group

Clinical Orthopaedics and Related Research®: April 2019 - Volume 477 - Issue 4 - p 789–801
doi: 10.1097/CORR.0000000000000411

Background During recent wars, 26% of combat casualties experienced open fractures and these injuries frequently are complicated by infections, including osteomyelitis. Risk factors for the development of osteomyelitis with combat-related open tibia fractures have been examined, but less information is known about recurrence of this infection, which may result in additional hospitalizations and surgical procedures.

Questions/purposes (1) What is the risk of osteomyelitis recurrence after wartime open tibia fractures and how does the microbiology compare with initial infections? (2) What factors are associated with osteomyelitis recurrence among patients with open tibia fractures? (3) What clinical characteristics and management approaches are associated with definite/probable osteomyelitis as opposed to possible osteomyelitis and what was the microbiology of these infections?

Methods A survey of US military personnel injured during deployment between March 2003 and December 2009 identified 215 patients with open tibia fractures, of whom 130 patients developed osteomyelitis and were examined in a retrospective analysis. No patients with bilateral osteomyelitis were included. Twenty-five patients meeting osteomyelitis diagnostic criteria were classified as definite/probable (positive bone culture, direct evidence of infection, or symptoms with culture and/or radiographic evidence) and 105 were classified as possible (bone contamination, organism growth in deep wound tissue, and evidence of local/systemic inflammation). Patients diagnosed with osteomyelitis were treated with débridement and irrigation as well as intravenous antibiotics. Fixation hardware was retained until fracture union, when possible. Osteomyelitis recurrence was defined as a subsequent osteomyelitis diagnosis at the original site ≥ 30 days after completion of initial treatment. This followup period was chosen based on the definition of recurrence so as to include as many patients as possible for analysis. Factors associated with osteomyelitis recurrence were assessed using univariate analysis in a subset of the population with ≥ 30 days of followup. Patients who had an amputation at or proximal to the knee after the initial osteomyelitis were not included in the recurrence assessment.

Results Of 112 patients meeting the criteria for assessment of recurrence, 31 (28%) developed an osteomyelitis recurrence, of whom seven of 25 (28%) had definite/probable and 24 of 87 (28%) had possible classifications for their initial osteomyelitis diagnosis. Risk of osteomyelitis recurrence was associated with missing or devascularized bone (recurrence, 14 of 31 [47%]; nonrecurrence, 22 of 81 [28%]; hazard ratio [HR], 3.94; 1.12–13.81; p = 0.032) and receipt of antibiotics for 22-56 days (recurrence, 20 of 31 [65%]; nonrecurrence: 37 of 81 [46%]; HR, 2.81; 1.05–7.49; p = 0.039). Compared with possible osteomyelitis, definite/probable osteomyelitis was associated with localized swelling at the bone site (13 of 25 [52%] versus 28 of 105 [27%]; risk ratio [RR], 1.95 [1.19-3.19]; p = 0.008) and less extensive skin and soft tissue injury at the time of trauma (9 of 22 [41%; three definite/probably patients missing data] versus 13 of 104 [13%; one possible patient missing data]; RR, 3.27 [1.60-6.69]; p = 0.001). Most osteomyelitis infections were polymicrobial (14 of 23 [61%; two patients with missing data] for definite/probable patients and 62 of 105 [59%] for possible patients; RR, 1.03 [0.72-1.48]; p = 0.870). More of the definite/probable patients received vancomycin (64%) compared with the possible patients (41%; p = 0.046), and the duration of polymyxin use was longer (median, 38 days versus 16 days, p = 0.018). Time to definitive fracture fixation was not different between the groups.

Conclusions Recurrent osteomyelitis after open tibia fractures is common. In a univariate model, patients with an intermediate amount of bone loss and those treated with antibiotics for 22 to 56 days were more likely to experience osteomyelitis recurrence. Because only univariate analysis was possible, these findings should be considered preliminary. Osteomyelitis recurrence rates were similar, regardless of initial osteomyelitis classification, indicating that diagnoses of possible osteomyelitis should be treated aggressively.

Level of Evidence Level III, therapeutic study.

J. L. Petfield, C. K. Murray, D. J. Stinner, San Antonio Military Medical Center, JBSA Fort Sam Houston, TX, USA

J. L. Petfield, Landstuhl Regional Medical Center, Landstuhl, Germany

D. R. Tribble, A. C. Weintrob, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

B. K. Potter, L R. Lewandowski, Department of Surgery, Uniformed Services University of the Health Sciences-Walter Reed National Military Medical Center, Bethesda, MD, USA

A. C. Weintrob, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA; and Walter Reed National Military Medical Center, Bethesda, MD, USA

M. Krauss, Westat, Rockville, MD, USA

J. L. Petfield, Orthopaedic Surgery Service, Landstuhl Regional Medical Center, CMR 402, APO, AE, 09180, email:

Funding for this work was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense program executed through the Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics. One or more of the authors (DRT, ACW) received grants paid toward their institution (Uniformed Services University of the Health Sciences) an amount of USD 100,001 to USD 1,000,000 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Interagency Agreement Y1-AI-5072; and an amount of more than USD 1,000,001 from the Department of the Navy under the Wounded, Ill, and Injured Program during the conduct of this study. One of the authors (MK) received other funding from IDCRP, an amount of USD 100,001 to USD 1,000,000, during the conduct of this study through a Westat contract to conduct the statistical analysis of the data.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA approval status, of any drug or device before clinical use.

Each author certifies that his or her institution approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Uniformed Services University of the Health Sciences (Bethesda, MD, USA), Walter Reed National Military Medical Center (Bethesda, MD, USA), Brooke Army Medical Center (JBSA Fort Sam Houston, TX, USA), and Landstuhl Regional Medical Center (Landstuhl, Germany).

Received December 11, 2017

Accepted June 27, 2018

© 2019 Lippincott Williams & Wilkins LWW
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