Abstract
Objectives: Antimicrobial therapy is one of the cornerstones of orthopaedic implant-related infections (OIRI) treatment. Infections with Gram-positive bacteria are often treated with vancomycin, penicillin or clindamycin. A recent IDSA guideline suggests increasing the dose of vancomycin to increase the trough vancomycin target serum concentrations. This is deemed necessary because of an observed decrease in vancomycin susceptibility among Gram-positive bacteria. However, elevated vancomycin concentrations are correlated with the risk of nephrotoxicity, especially with prolonged therapy. Compared to most countries, rates of resistance against antibiotics among bacteria in the Netherlands are lower for currently available antibiotics, therefore lower target concentrations of vancomycin are probably efficacious for the treatment of infections.In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, as an initial therapy for OIRI, and compared this with long-term penicillin and clindamycin therapy, as initial therapy, in patients with Gram-positive orthopaedic implant-related infections.Methods: A retrospective, observational study was conducted in 103 adult patients treated for OIRI, with vancomycin, penicillin or clindamycin for at least 10 days. The target trough serum concentration of vancomycin was 10-15 mg/l.Results: 74% of our patients were treated successfully with vancomycin, as initial therapy, (no reinfection within 1 year) versus 55% of our patients treated with either an antibiotic of the penicillin class (mostly flucloxacillin) or clindamycin (p=0.08), as initial therapy. For patients treated with vancomycin we observed a serum creatinine increase of 6 μmol/l, for patients treated with either an antibiotic of the penicillin class or clindamycin the serum creatinine increase was 4 μmol/l (p=0.395).Conclusions: In our population of patients with OIRI long-term treatment with conventionally dosed vancomycin, as initial therapy, was not significantly less effective and safe as long-term treatment with an antibiotic of the penicillin class or clindamycin, as initial therapy.
Highlights
Vancomycin, a glycopeptide antibiotic, is often used in combination with surgical interventions, in the treatment of patients with orthopaedic implantrelated infections (OIRI), caused by Gram-positive micro-organisms, which are not susceptible to either an antibiotic of the penicillin class (e.g amoxicillin, benzylpenicillin, flucloxacillin) or clindamycin
In this study we evaluated the efficacy and safety of long-term conventionally dosed vancomycin therapy, and compared these with long-term penicillin and clindamycin therapy, the antibiotic regimens that are regularly prescribed in patients with Gram-positive orthopaedic implant-related infections
For patients treated with vancomycin we observed an increase of 6 μmol/l, for patients treated with either penicillin or clindamycin the increase was 4 μmol/l
Summary
Vancomycin, a glycopeptide antibiotic, is often used in combination with surgical interventions, in the treatment of patients with orthopaedic implantrelated infections (OIRI), caused by Gram-positive micro-organisms, which are not susceptible to either an antibiotic of the penicillin class (e.g amoxicillin, benzylpenicillin, flucloxacillin) or clindamycin. In the most recent guideline of IDSA (Infectious Diseases Society of America), [3] a higher trough concentration of 15-20 mg/l has been suggested though, related to an expected reduced susceptibility of the micro-organisms for vancomycin (MIC > 1mg/l). This worldwide used guideline is mainly based on research in (methicillin resistant) Staphylococcus aureus infected patients, treated with vancomycin, from the United States where a decreased susceptibility to vancomycin has been observed among Staphylococcus spp. A recent meta-analysis showed an odds ratio of 2.7 for nephrotoxicity in patients treated with vancomycin doses leading to troughs > 15 mg/l compared to patients treated with doses leading to troughs ≤15 mg/l. [6] implementing new guidelines aiming at higher vancomycin serum concentrations should be considered carefully
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