Continued Dosing of Oritavancin for Complicated Gram-Positive Infections

In a published case series, 1 of 10 patients receiving oritavancin for invasive Grampositive infections received multiple doses of oritavancin for an MSSA deep tissue infection.¹¹ The 3 total doses (strength not reported) were separated by 19 days and 14 days and resulted in cure. Several case reports and a retrospective chart review study specifically show the effectiveness of oritavancin for osteomyelitis caused by MSSA, MRSA, and VRE.^12-16 However, dosing strategies varied widely after the initial 1,200 mg IV loading dose.

Drug Interactions, Safety, and Tolerability

Oritavancin has minimal drug-drug interactions, the most notable being with anticoagulants. ¹ Use of IV heparin within 120 hours of oritavancin administration can falsely elevate activated partial thromboplastin time (aPTT) levels; therefore, heparin should not be monitored with aPTT during this period. Oritavancin also can artificially prolong international normalized ratio (INR) values for up to 12 hours, and dose adjustments based on INRs during this window are not recommended. Of note, factor Xa laboratory monitoring is unaffected by oritavancin, as it does not depend on phospholipid reagents as do aPTT and INR measurements.

Oritavancin has been shown to be well tolerated when dosed according to both the package insert and continued dosing strategies. The most common adverse effects (AEs) (≥ 3%), occurring at similar rates to vancomycin, are nausea, vomiting, diarrhea, headache, and limb and subcutaneous abscesses.¹ Infusion reactions also have been reported, although they are usually reversible on slowing or stopping the infusion. It is worth noting that the use of oritavancin for osteomyelitis is not recommended in the product labeling, as an increased rate of osteomyelitis was observed in the oritavancin vs IV vancomycin groups for the treatment of patients with acute bacterial skin and skin structure infection (SOLO) trials (0.6% in oritavancin group vs 0.1% in vancomycin group, statistical significance not reported).¹⁷ However, it was postulated that these osteomyelitis cases were likely present, yet not recognized, at baseline and were not the result of administering oritavancin. This conclusion is further corroborated by previously presented research demonstrating successful cure of osteomyelitis with continued dosing strategies.^12-16

Many patients receiving multiple doses of oritavancin did not experience AEs or laboratory abnormalities.^13,15 Four of 17 patients (24%) in one retrospective review experienced AEs, including infusion reactions, anemia, and leukopenia; all were reversible on discontinuation of oritavancin, and contributions of other antibiotics in some cases could not be ruled out.¹⁰ One patient experienced taste disturbance for several hours after each infusion, and a second had documented hearing loss after 3 doses of oritavancin in a 33-day period, though she had received 6 weeks of IV vancomycin prior to oritavancin.^11,12 A patient treated for daptomycin- and vancomycinresistant Enterococcus faecium prosthetic valve endocarditis experienced nausea, anorexia, and minor liver function test (LFT) abnormalities after cumulative oritavancin exposure over 18 weeks.⁹ On discontinuation of the drug, nausea and anorexia improved, and LFTs normalized 11 months later. Overall, AEs reported with continued dosing of oritavancin have been minimal and largely reversible, mimicking the AEs in the product labeling for traditional dosing. This suggests that using a continued dosing strategy may not result in worse or more frequent AEs, though randomized controlled trials are needed to fully ascertain these preliminary findings.

Conclusions

The literature supporting the use of oritavancin beyond single-dose administration for ABSSSI is growing. Continued dosing regimens have been well tolerated and have resulted in clinical cure for many patients with barriers to first-line treatment and complicated or invasive infections. While randomized controlled trials are needed to concretely demonstrate the efficacy and safety of continued dosing of oritavancin, it may fill an important treatment niche in this era of growing antibiotic resistance and increasing complexity of patient cases.