Oritavancin 400mg powder for solution for infusion vials

Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), E. faecalis (13) and E. faecium (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.

Abstract licence: CC BY 4.0

Background and objectivesOritavancin 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.Materials and methodsFollowing the PRISMA 2020 Statement and adopting the PICO strategy, a comprehensive search was conducted in PubMed, Scopus and Cochrane databases up to September 2025.ResultsOf 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.ConclusionsThe 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.

Abstract licence: CC BY 4.0

Randomized controlled trials (RCTs) sponsored by pharmaceutical manufacturers for regulatory approval are conducted with restrictive criteria in an effort to definitively demonstrate the safety and efficacy of a drug or biologic. Unfortunately, the strict enrollment criteria in RCTs may exclude patients likely to receive the medication in a real-world clinical practice. Antibiotic RCTs for registration are designed to show noninferiority against standard of care or best available therapy, often minimizing clinical differentiation needed by clinicians to select the optimal agent for their patients. Lastly, RCTs do not include pharmacoeconomic data that would add a cost basis for determining the value of one product over another. Real-world studies may add support to the safety and efficacy demonstrated from RCTs and address patient populations excluded from clinical development programs. This supplement presents several real-world studies demonstrating the clinical and economic outcomes of various uses of oritavancin to augment the evidence published from RCTs. Clinicians may decide how to use this information in their own practice settings.

Abstract licence: CC BY-NC 4.0