Yesterday, the NEJM published two new trials regarding new lipoglycopeptide antibiotics targeting MRSA. And, it remains to be seen whether their use represents the beginning of the end.
Oritavancin and dalbavancin differ from vancomycin – and this is their primary advertised advantage – in terms of substantially lengthened terminal half-life. This means oritavancin may be used as a one-time dose, and dalbavancin as a two-dose regimen a week apart. Both trials involved severe soft-tissue infection, and were non-inferiority trials comparing each against either intravenous vancomycin alone or intravenous vancomycin transitioning to oral linezolid. Exclusion criteria were extensive for each, but the ultimate non-inferiority results for treatment failure are reasonably generalizable. Adverse events, as well, were similar between study populations. At face validity – if you trust trials that are designed, conducted, and analyzed by pharmaceutical companies – these treatments are safe and effective.
The accompanying editorial enthusiastically supports these new options, saving patients unnecessary costs and risks associated with hospitalization or indwelling intravenous catheters. This is likely true, although it remains to be see whether single-dose infusion pricing will ultimately prove less expensive than a transition to oral linezolid. Then, single-dose antibiotic strategies may have a horrible downside: induced resistance. With terminal half-lives up to two weeks in the case of oritavancin, the active metabolite will be present in the body for a prolonged period of time below the minimum inhibitory concentration. As we’ve seen with azithromycin, another antibiotic with a long half-life, increased use was associated with a rapid rise in macrolide resistant streptococcus. It’s hardly a stretch to project similar effects here.
Widespread use of these “convenient” antibiotics may eventually result in significant unintended harms, and possibly the loss of an entire class of effective treatment for MRSA.
“Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection”
http://www.nejm.org/doi/full/10.1056/NEJMoa1310480
“Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections”
http://www.nejm.org/doi/full/10.1056/NEJMoa1310422