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Single, high-dose Dalvance infusion noninferior to two-dose regimen
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Delivery of Dalvance in a single dose could result in safety and efficacy outcomes similar to those provided by the currently approved schedule, which breaks the antibiotic treatment into two separate infusions, according to new data published in Clinical Infectious Diseases.
“Currently approved therapy is given as two doses 1 week apart, a regimen made possible by its terminal half-life of 15.5 days,” Michael W. Dunne, MD, chief medical officer at Allergan, and colleagues wrote. “Based on the principle that treatment for infection should be given early in the course of therapy while the bacterial burden is highest and the likelihood of compliance is greatest, further studies to optimize the treatment course were warranted.”
Efficacy, safety similar between treatments
From April 2014 to March 2015, Dunne and colleagues enrolled patients with acute bacterial skin and skin structure infection (ABSSSI) receiving care at 60 worldwide health care centers into the double blind, pharmacist unblended, randomized trial. Participants were administered Dalvance (dalbavancin, Actavis) either as a 30-minute, 1,000 mg IV infusion followed by 500 mg on day 8, or single IV infusion of 1,500 mg and placebo on day 8.
Patients with catheter infections, infected devices, diabetic foot ulceration, perirectal abscess, decubitus ulcer, or had taken antibiotics other than a single dose, short half-life drug within 14 days were excluded from the study. Study outcomes included the proportion of patients who achieved a 20% or greater reduction in erythema size within 48 to 72 hours of treatment initiation, improved clinical status at day 14 and day 28, and safety through day 28.
Among the 695 patients who received dalbavancin at baseline and were included in safety analysis, 93.1% also received either a second dose or placebo at day 8, and 87% were eligible for clinical evaluation on day 14. Approximately 12% of the cohort had diabetes, 5% without diabetes had a random baseline glucose level greater than 200 mg/dL, 30.4% were IV drug users, and 16.2% had hepatitis C virus. Cellulitis was the most frequent infection subtype (48%), followed by traumatic wound/surgical site infection (27%) and major abscess (25%).
Erythema size reductions at 48 to 72 hours occurred in 81.4% of patients receiving the single-dose regimen and 84.2% of those in the standard regimen. Clinical success and safety also were similar between groups, and similar rates of positive outcomes were seen regardless of whether patients were treated during hospitalization or as outpatients. In addition, cultures collected at baseline and during follow-up revealed no development of resistance in either group.
“The option to use a single or two-dose regimen of dalbavancin introduces flexibility into the treatment decision of ABSSSI,” Dunne and colleagues wrote. “Some patients are less likely to return for follow-up than others, and this study documents that compliance with a single dose regimen is superior to that of even a very simple weekly, two-dose regimen.
“Physicians can now make a rational choice between a single dose regimen and a weekly dose regimen that recognizes a patient’s social circumstance and tailors the regimen for that individual patient’s needs.”
Dalbavancin comparable to daily vancomycin
Dalbavancin was designated as a Qualified Infectious Disease Product under the Generating Antibiotic Incentives Now (GAIN) Act in October 2012 due to its effectiveness in treating MRSA. In March 2014, the FDA Anti-Infective Drugs Advisory Committee unanimously found the antibiotic safe and effective for the treatment of ABSSSI caused by multiple gram-positive organisms.
Dalbavacin infusions also may be a viable option to daily vancomycin treatments, according to findings published last year by Dunne and colleagues. In the DISCOVER-1 and DISCOVER-2 trials, the researchers examined 573 adults from 140 global site with ABSSSI receiving either the standard, two-dose dalbavacin or vancomycin every 12 hours for 3 days or more, with an option to switch to oral Zyvox (linezolid, Pfizer) 600 mg every 12 hours.
Dunne and colleagues reported favorable early clinical responses in 83.3% of patients in the dalbavancin group and 81.8% of vancomycin-linezolid patients in DISCOVER-1, while 76.8% patients had an early clinical response within the dalbavancin group and 78.3% had an early clinical response within the vancomycin-linezolid group in DISCOVER-2. When pooled, analysis showed these outcomes in 79.7% of the dalbavancin group and 79.8% of the vancomycin-linezolid group.
Causes of treatment failure also were similar between treatment groups; adverse event were less frequent among the dalbavancin arm.
“The results of these trials showed the noninferiority of dalbavancin administered once weekly as compared with vancomycin-linezolid administered twice daily for the treatment of ABSSSI in seriously ill patients,” they concluded. – by Dave Muoio
Disclosure: Dunne reports holding stock in Durata Therapeutics and employment at Actavis at the time of study publication. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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C. Buddy Creech, MD, MPH
Surgeon General C. Everett Koop is famous for once saying, “Drugs don’t work in patients who don’t take them.”
While true of all medications, the consequences for noncompliance with antimicrobial agents has both a personal and a societal impact as patients experience treatment failures and cultivate antibiotic-resistant pathogens. Thus, the notion that a single dose of dalbavancin is effective for many patients with acute bacterial skin and skin structure infection is an important advancement, particularly for patients with a low likelihood of returning for care and those in whom outpatient parenteral therapy is unwise.
While seemingly an incremental improvement over the currently approved two-dose schedule (administered one week apart), one-time dosing may offer tremendous value and effectiveness for such patients.
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