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Mismatch Rate of Empirical Antimicrobial Treatment in Fracture-Related Infections
Michelle M J Jacobs1, Micha Holla1, Bas van Wageningen2
1Department of Orthopaedic Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands.
Objectives:
To evaluate the current standard of care regarding empirical antimicrobial therapy in fracture-related infections (FRIs).
Design:
Retrospective cohort study.
Setting:
Level I Trauma Center.
Patient Selection Criteria:
Adult patients treated for FRI with surgical debridement and empirical antibiotics between September 1, 2014, and August 31, 2022. Patients were excluded if less than 5 tissue samples for culture were taken, culture results were negative, or there was an antibiotic-free window of less than 3 days before debridement.
Outcome Measures And Comparisons:
FRI microbial etiology, antimicrobial resistance patterns (standardized antimicrobial panels were tested for each pathogen), the mismatch rate between empirical antimicrobial therapy and antibiotic resistance of causative microorganism(s), and mismatching risk factors.
Results:
In total, 75 patients were included [79% (59/75) men, mean age 51 years]. The most prevalent microorganisms were Staphylococcus aureus (52%, 39/75) and Staphylococcus epidermidis (41%, 31/75). The most frequently used empirical antibiotic was clindamycin (59%, 44/75), followed by combinations of gram-positive and gram-negative covering antibiotics (15%, 11/75). The overall mismatch rate was 51% (38/75) [95% confidence interval (CI), 0.39-0.62] and did not differ between extremities [upper: 31% (4/13) (95% CI, 0.09-0.61), lower: 55% (33/60) (95% CI, 0.42-0.68, P = 0.11)]. Mismatching empirical therapy occurred mostly in infections caused by S. epidermidis and gram-negative bacteria. Combination therapy of vancomycin with ceftazidime produced the lowest theoretical mismatch rate (8%, 6/71). Polymicrobial infections were an independent risk factor for mismatching (OR: 8.38, 95% CI, 2.53-27.75, P < 0.001).
Conclusions:
In patients with FRI, a mismatching of empirical antibiotic therapy occurred in half of patients, mainly due to lack of coverage for S. epidermidis , gram-negative bacteria, and polymicrobial infections. Empirical therapy with vancomycin and ceftazidime produced the lowest theoretical mismatch rates. This study showed the need for the consideration of gram-negative coverage in addition to standard broad gram-positive coverage. Future studies should investigate the effect of the proposed empirical therapy on long-term outcomes.
Level Of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Insights
Half of fracture-related infection (FRI) patients received mismatched empirical antibiotic therapy, often lacking coverage for Staphylococcus epidermidis and gram-negative bacteria. Vancomycin and ceftazidime combination showed the lowest mismatch rates, suggesting improved empirical strategies for FRIs.
Area of Science:
- Orthopedics
- Infectious Diseases
- Pharmacology
Background:
- Fracture-related infections (FRIs) pose significant challenges in orthopedic surgery.
- Current empirical antimicrobial therapy for FRIs often lacks targeted coverage, leading to suboptimal treatment outcomes.
Purpose of the Study:
- To evaluate the effectiveness of current empirical antimicrobial therapy standards for fracture-related infections.
- To identify microbial etiologies, resistance patterns, and mismatch rates in FRIs.
Main Methods:
- Retrospective cohort study of 75 adult patients with FRIs treated with debridement and empirical antibiotics.
- Analysis of microbial etiology, antimicrobial resistance, and mismatch rates between prescribed and causative pathogens.
- Evaluation of risk factors for empirical therapy mismatch.
Main Results:
- A 51% mismatch rate was observed between empirical antibiotic therapy and causative microorganisms in FRIs.
- Staphylococcus aureus and Staphylococcus epidermidis were the most prevalent pathogens.
- Polymicrobial infections significantly increased the risk of mismatch (OR: 8.38).
- Vancomycin combined with ceftazidime demonstrated the lowest theoretical mismatch rate (8%).
Conclusions:
- Empirical antibiotic therapy for FRIs frequently mismatches the causative pathogens, particularly for S. epidermidis, gram-negative bacteria, and polymicrobial infections.
- The study highlights the need to incorporate gram-negative coverage into standard empirical antibiotic regimens for FRIs.
- Vancomycin and ceftazidime combination therapy shows promise for reducing empirical therapy mismatch in FRIs.
