Extrapolation of oritavancin PK/PD targets to inform therapeutic drug monitoring: a systematic review

Resumo original em inglês

O que aconteceu

Oritavancin is a lipoglycopeptide with sustained bactericidal activity against Gram-positive bacteria due to its prolonged half-life. This Systematic Review aimed to extrapolate, from in vitro/in vivo or clinically study, the most relevant PK/PD target to inform therapeutic drug monitoring-guided oritavancin dose optimization in clinical practice.

Following the PRISMA 2020 Statement and adopting the PICO strategy, a comprehensive search was conducted in PubMed, Scopus and Cochrane databases up to September 2025.

O que encontraram

Of 186 articles screened, 52 were considered eligible for full-text assessment. Nine studies were included and proceeded with data extraction and synthesis steps. In vitro studies showed a marked concentration-dependent bactericidal activity at fCmax > 4-16 mg/L against different bacterial strains, further confirmed by in vivo animal models (fCmax/MIC > 6 to 14). However, the only identified in-human daily repeated doses study supported the findings of an exposure-response relationship with %fT > MIC as predictive of microbiological and clinical success.

Por que isso importa

The peculiar pharmacokinetics profile of oritavancin results in a borderline collinearity between the two PK/PD indices fCmax/MIC and %fT > MIC in relation to microbiological and clinical success rates. On the basis of available in vitro/in vivo data supporting concentration-dependent killing activity, a single 1200 mg oritavancin dose should be adequate for most infections. In special patient populations, or when multidose oritavancin regimens are adopted for long-term antibiotic treatment, therapeutic drug monitoring supported by expert clinical pharmacological advice may be valuable to optimize the initial and next-dose strategy (1200 mg or 800 mg) and to define the timing of re-administration.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.