Long-Acting Lipoglycopeptides for the Treatment of Severe Infections

Long-acting lipoglycopeptides (LGPs) including dalbavancin, oritavancin, and telavancin were developed with their unique pharmacokinetic property of prolonged half-lives. The initial registry trials primarily included patients with acute bacterial skin and skin structure infections (ABSSSIs).^1,2,3 In recent years, more data has emerged for their use in other infections such as infective endocarditis (IE), bone and joint infections (BJIs), and bloodstream infections (BSIs) as an alternative to standard-of-care (SOC) and outpatient parenteral antimicrobial therapy (OPAT) (Table 1).⁴ Key limitations amongst currently available studies are:

1) retrospective and observational design,

2) small sample size, case series, or case reports, particularly for oritavancin and telavancin,

3) lack of comparator group (single arm studies),

4) different definitions for clinical efficacy, and

5) heterogenous dosing regimens and durations of therapy.

While not fully published, the preliminary data from a multicenter, randomized controlled trial (DOTS trial) evaluating the use of dalbavancin for the treatment of complicated Staphylococcus aureus bacteremiafollowing blood culture clearance, demonstrated non-inferiority to SOC.5 The purpose of this article is to provide a scoping review of literature evidence evaluating the use of LGPs in severe infections.

ADE = adverse drug event; AKI = acute kidney injury; BSI = bacteremia; CDI = Clostridioidies diffilce infection; CoNS = coagulase negative Staphylococcus; CLABSI = central line associated bloodstream infection; DAIR = debridement, antibiotic and implant retention; DM = diabetes mellitus; IE = infective endocarditis; IV = intravenous; LOS = length of stay; MSSA = methicillin susceptible Staphylococcus aureus; MRSA = methicillin resistant Staphylococcus aureus; NVIE = native valve infective endocarditis; OM = osteomyelitis; PCN = penicillin; PICC = peripherally inserted central catheter; PJI = prosthetic joint infection; PWID = persons who inject drugs; RCT = randomized controlled trial; SAB = Staphylococcus aureus bacteremia; SOC = standard of care; SUD = substance use disorder; SSTI = skin and soft tissue infection

Summary

Although FDA-approved for the treatment of ABSSSIs, the greatest niche for LGPs may be for the treatment of more severe infections such as IE, BJIs, and BSIs. The convenience provided by less frequent dosing, in tandem with a growing body of supporting data, offers providers an alternative treatment option for complex cases where avoiding central-line placement and daily infusions post-discharge may be most ideal. The treatment of severe infections with LGPs has so far been limited to small, heterogeneous, retrospective studies and case reports. However, a few RCTs provide the largest body of evidence demonstrating that dalbavancin is as good as SOC therapies for treatment. Currently, the greatest evidence for the use of LGPs is for BJIs.4 More standardized, larger-scale studies that can provide higher quality evidence would help to solidify the role of these agents for these more complicated infections. In addition, more guidance is needed surrounding which doses and durations of therapy are most ideal for certain indications. No studies exist differentiating the efficacy and safety of different dosing strategies or optimal durations of therapy with LGPs for each disease state.

Overall, the limitations of currently available literature prohibit widespread adoption of LGPs in place of SOC therapies; however, dalbavancin and oritavancin may be considered as reasonable alternatives to SOC on a case-by-case basis with risk: benefit consideration (eg dalbavancin for IE, BJIs, and BSIs and oritavancin for BJIs and BSIs). Such cases where the use of LGPs would be beneficial were highlighted in a recent statement released in 2022 by the American Heart Association (AHA) for the Management of Infective Endocarditis in People Who Inject Drugs. The statement specifically supports using LGPs (dalbavancin and oritavancin) or oral agents for patients who cannot complete six weeks of IV treatment.³⁰ To date, there is insufficient evidence available to support telavancin as an alternative to SOC for these severe infections when other agents are available.

This is the first piece in a 3-part series. Check back next week for the second part in the series, which will cover a long-acting injectable for the treatment of Candida spp. Infections.

References

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