MRSA: Where Do We Go From Here?
- Volume 18 - Issue 3 - March 2005
- 27912 reads
- 0 comments
In two large clinical trials with a cohort of more than 1,000 patients with cSSTIs, researchers compared the safety and efficacy of daptomycin with penicillinase-resistant penicillins or vancomycin.43 The trial included 61 patients (11 percent) with infected ulcers in the daptomycin group and 72 (13 percent) in the comparator group. There were 40 patients with MRSA (9.3 percent) in the daptomycin group and 47 patients with MRSA (10 percent) among patients receiving comparator agents.
The success rates for the clinically evaluable population were 83.4 percent for those in the daptomycin group and 84.2 percent for those in the comparator group.43 Clinical success rates for patients with infections caused by both S. aureus and hemolytic streptococci were 76 percent for those treated with daptomycin and 70 percent for patients treated with comparator drugs. In the subgroup of patients with an infected ulcer, there was a 66 percent success rate in the daptomycin group versus a 70 percent rate in the comparator group. Clinical success rates for cSSTIs caused by MRSA were 75 percent for patients receiving daptomycin and 69.4 percent for the comparator group.
Safety and tolerability were similar in both arms of the trial. Only 15 participants (2.8 percent) receiving daptomycin discontinued treatment due to adverse events as did a similar number (17 patients or 2.8 percent) in the comparator group.
Dalbavancin: Does This Emerging Agent Have Promise?
Currently in development, dalbavancin is a novel intravenous semisynthetic glycopeptide that has shown activity against a wide range of gram-positive bacteria including staphylococci, streptococci, enterococci, Corynebacteria species, selected strains of vancomycin-resistant enterococci (VRE), vancomycin-intermediate S. aureus and MRSA.44-46
Although its mechanism of action is similar to that of other glycopeptides, dalbavancin has not demonstrated the same degree of cross resistance to vancomycin and appears to have activity against vancomycin-resistant van-beta phenotypic enterococci.45 A unique feature of dalbavancin is its very long half life, which results from extensive and reversible binding to plasma protein, primarily albumin.47-49 The mean plasma concentration of dalbavancin is greater than 35 mg/L for one week, following a single intravenous dose of 1 gram.47
In a randomized, controlled, open-label, phase II trial by Seltzer, et. al., the researchers randomized 62 patients with a cSSTI — suspected or known to be caused by gram-positive bacteria — to receive either a single dose of dalbavancin, two doses of dalbavancin given a week apart or a treatment with a comparator regimen.50
Researchers isolated a gram-positive organism in 41 of the patients and the majority of these were monomicrobial. S. aureus was the most frequent organism isolated, comprising 83 percent of pathogens. Clinical success rates for patients infected with MRSA were 80 percent (four of five patients) in the group that received two doses of dalbavancin; 50 percent (three of six patients) for those who received a single dose; and 50 percent (one of two patients) for the comparator regimens.
In another study, researchers tested dalbavancin and selected comparators against 6,336 clinical isolates of gram-positive organisms, which included oxacillin-resistant S. aureus, VRE and penicillin-nonsusceptible pneumococci.51 The minimum inhibitory concentration (MIC) values of dalbavancin ranged from less than or equal to 0.015 g/mL to greater than 32 g/mL. However, more than 99 percent of MIC results were at less than or equal to 1 g/mL. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (the minimum concentration required to inhibit 90 percent of organisms [MIC90] was 0.06 g/mL), despite exhibiting resistance patterns to other antimicrobial agents.