Journal Club
In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.
- Oritavancin for Gram-Positive Infections in the Real World: Hope or Hype?
- Ninety-Six Week Data for Dolutegravir and Lamivudine in Adults with HIV
Did you miss the previous edition of Journal Club? You can find it and other past installments in the IDSA News archives. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, M.D., FIDSA, in each issue of Clinical Infectious Diseases.
Oritavancin for Gram-Positive Infections in the Real World: Hope or Hype?
Reviewed by A. Krishna Rao, M.D., M.S.
Oritavancin is a long-acting lipoglycopeptide molecule, developed in part with the goal of avoiding or shortening hospitalization. It can accomplish this given a half-life of > 200 hours, allowing the original clinical trials to demonstrate noninferiority when administered as one 1,200 mg intravenous (IV) infusion given over 3 hours compared to 7–10 days of twice daily vancomycin. It is bactericidal against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The trials, however, focused on acute bacterial skin and skin structure infection (ABSSSI), and clinicians need information about its efficacy for other conditions and clinical scenarios where daily IV medication administration is not desirable.
This retrospective, observational study published in Open Forum Infectious Diseases provides a real-world description of the use of oritavancin for multiple different infections among 440 subjects from 26 sites. Subjects were included if they had suspected Gram-positive infection and received at least one dose of oritavancin. Investigators used electronic case report forms to assess vital signs, laboratory parameters, and clinical findings such as cessation of spreading or reduction in size of the baseline lesion. These assessments in turn led to the definitions of clinical cure (all signs and symptoms resolved) and clinical failure (inadequate resolution, new or worsening signs/symptoms, or need for additional non-oritavancin therapy for treatment of the baseline infection). The analyses were descriptive only.
They enrolled 401 (91.1%) patients with ABSSSI (cellulitis, wound infection, and abscess) and 39 others with complicated Gram-positive infections including seven with bacteremia, 18 (4.1%) with osteomyelitis and 11 (2.5%) with bone/joint infections. Pathogens included S. aureus (both MRSA and MSSA) and various Streptococci (groups A, B, and viridans). Oritavancin resulted in clinical cure overall in 89% of subjects with ABSSSI and in 100% with bacteremia. The success with complicated Gram-positive infections overall was 93.8%, notably high with the bone/joint (90.9%) and osteomyelitis (87.5%) subgroups. Only 6.6% had adverse events, none severe or life-threatening. Of 32 (7.3%) patients receiving multiple doses, 11 were for osteomyelitis and other bone/joint infections, and the mean total number of doses was 3.3 (range 2–10).
In summary, this study provides real-world data in support of the hype surrounding oritavancin, not only observing high success rates for ABSSSI but also for other complicated Gram-positive infections. Given that this study was retrospective, observational, and only descriptive, our conclusions should be tempered. However, as we gather more data, one can hope that oritavancin remains an attractive option for patients who have issues that would make daily IV antibiotic administration difficult, such as with insurance coverage, post-discharge placement, or IV substance abuse. We are still in the early period after its initial approval—oritavancin may yet find a niche for treating conditions that require long courses of therapy, such as osteomyelitis, but time will tell if there is hope or if the promise was all hype.
(Redell et al. Open Forum Infect Dis. 2019:6(11):ofz479.)
Ninety-Six Week Data for Dolutegravir and Lamivudine in Adults with HIV
Reviewed by Lauren Richey, M.D., MPH, FIDSA
Despite early failures of two-drug regimens, there has been renewed interest as these regimens could cost less as well as decrease drug exposure and side effects. Ninety-six week results from GEMINI-1 and GEMINI-2, two identical, double-blind, non-inferiority studies conducted at 187 centers in 21 countries, were recently reported in JAIDS.
Adults living with HIV with less than 10 days of any antiretroviral therapy and a viral load of 1,000 to 500,000 copies/mL were included. Women were eligible if not pregnant or lactating and using effective contraception. Exclusion criteria included any major viral resistance mutation and stage three HIV disease (except for CD4 less than 200 and cutaneous Kaposi’s sarcoma). Patients were randomized to either dolutegravir/lamivudine or dolutegravir/emtricitabine/tenofovir disoproxil. The primary end point was the proportion with viral loads < 50 copies/mL at 96 weeks. Over 700 participants were randomized to each group, mostly white (69%) males (85%). Few had advanced disease, with a viral load > 100,000 (20%) and CD4 < 200 (8%).
Among the dolutegravir/lamivudine group, 85.5% were virally suppressed at 96 weeks, 88.8% in the dolutegravir/emtricitabine/tenofovir disoproxil group. Based on a predefined 10% inferiority margin, dolutegravir/lamivudine was non-inferior. Eleven participants in the dolutegravir/lamivudine group and seven in the dolutegravir/emtricitabine/tenofovir disoproxil group were discontinued from the study due to virologic failure parameters set by the researchers. No one in either group, however, had resistance by genotypic and phenotypic testing. The dolutegravir/lamivudine group had a slightly lower rate of drug-related adverse events (20% versus 25%).
Overall, the study showed two drugs, dolutegravir/lamivudine, to be tolerable and virologic outcomes that were non-inferior at 96 weeks in initial therapy for people living with HIV, compared with a similar three-drug regimen. However, given the trend towards starting antiretroviral therapy as soon as possible and the need to exclude major resistance mutations by genotype, which are not uncommon and can take 2-3 weeks, it is unclear how often this will be a viable initial regimen.
(Cahn et al. JAIDS. Published online: Dec. 10, 2019.)