What Is the Most Effective Empirical Antibiotic Treatment for Early, Delayed, and Late Fracture-Related Infections?

Abstract

Antibiotic treatment strategies for fracture-related infections (FRI) are often extrapolated from periprosthetic joint infections (PJI), although, in contrast to PJI, detailed analysis of pathogens and their antibiotic resistance is missing. Therefore, this study aimed to investigate antibiotic susceptibility profiles to identify effective empiric antibiotic treatment for early-, delayed-, and late-onset FRI. Patients treated for FRI from 2013 to 2020 were grouped into early (<2 weeks), delayed (3–10 weeks), and late (>10 weeks) onset of infection. Antibiotic susceptibility profiles were examined with respect to broadly used antibiotics and antibiotic combinations. In total, 117 patients (early n = 19, delayed n = 60, late n = 38) were enrolled. In early-onset FRI, 100.0% efficacy would be achieved by meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide, ciprofloxacin + glycopeptide and piperacillin/tazobactam + glycopeptide. For patients with delayed FRI, the highest susceptibility was revealed for meropenem + vancomycin, gentamicin + vancomycin and ciprofloxacin + glycopeptide (96.7%). Meropenem + vancomycin was the most effective empiric antimicrobial in patients with late-onset of infection with 92.1% coverage. No subgroup differences in antibiotic sensitivity profiles were observed except for the combination ciprofloxacin + glycopeptide, which was significantly superior in early FRI (F = 3.304, p = 0.04). Across all subgroups meropenem + vancomycin was the most effective empiric treatment in 95.7% of patients with confirmed susceptibility. Meropenem + vancomycin, gentamicin + vancomycin, co-amoxiclav + glycopeptide are the best therapeutic options for FRI, regardless of the onset of infection. To avoid multidrug resistance, established antibiotic combinations such as co-amoxiclav with a glycopeptide seem to be reasonable as a systemic antibiotic therapy, while vancomycin + gentamicin could be implemented in local antibiotic therapy to reduce adverse events during treatment.

The Microbiological Etiology of Fracture-Related Infection

“…Unfortunately, documentation of haematogenous seeding is lacking, as is often the case in fracture-related infection studies. A few studies reported a predominance of S. aureus in each time interval ( Kuehl et al., 2019 ; Baertl et al., 2022 ), whereas in our study, S. aureus predominated in the delayed and late onset group.…”

“…A recent paper evaluated empirical antibiotic therapy according to onset of FRI. No significant differences in the potential efficacy of empiric antimicrobial regimens were observed between early, delayed and late-onset FRI, except for early FRI, in which the combination ciprofloxacin and glycopeptide was superior as compared to delayed and late FRI ( Baertl et al., 2022 ). Fluoroquinolone susceptibility was not evaluated in our cohort, because selection of resistance to these agents is possible when the bioburden is high, which makes them not suitable as empirical agent ( Greenberg et al., 1987 ; Aboltins et al., 2011 ).…”

“…Little is known about the value of this classification regarding the microbiological spectrum at time of debridement. A recent publication did not report significant differences in the pathogen distribution between the three subgroups ( Baertl et al., 2022 ).…”

Causative Pathogens Do Not Differ between Early, Delayed or Late Fracture-Related Infections

“…Since the publication of the definition of fracture-related infection (FRI) in 2018 [ 3 ], numerous researchers have attempted to clarify and unify optimal treatment, including both the surgical [ 4 ] and antimicrobial components [ 5 , 6 ]. In 1986, it was proposed that the time since fracture fixation was a key determinant of FRI management [ 7 ], based upon the hypothesized differences in causative pathogens in early (<2 weeks since fixation), delayed (3–10 weeks) and late (>10 weeks) infections.…”

“…However, there is ambiguity over whether these time intervals refer to time since injury [ 14 ], time since fixation [ 4 , 6 , 11 ] or time since symptom onset [ 8 ] and which, if any, definition is most clinically relevant. Furthermore, if managed with appropriate surgery, time from injury alone does not affect outcome in FRI [ 15 ].…”