Pharmacy and Therapeutics - January 2008 - (Page 45) DRUG FORECAST with trauma (25%), postsurgical infections (10%), bites (6%), or other causes (6%). Primary types of infections were abscesses (30%) and cellulitis (27%). The pathogens isolated included S. aureus (89%), S. pyogenes (5%), S. agalactiae (4%), Viridans streptococci (4%), and group C and G streptococci (1%–3%). The primar y efficacy endpoint was clinical success at the test-of-cure (TOC) visit at 14 ± 2 days (i.e., 12 to 16 days) after the completion of treatment with study medications. Clinical cure was also assessed at end-of-therapy visit within three days after completion of treatment with antibiotics. Of the 854 treated patients in this study, 82% were clinically evaluable at the end of therapy and 77% were evaluable at the TOC visit. At the TOC visit, 88.9% of the patients receiving dalbavancin and 91.2% of the linezolidtreated patients achieved clinical success, thereby showing the non-inferiority of dalbavancin. Additional results of end-of-therapy and TOC visits, as well as clinical and microbiologic success rates, are presented in Table 2. Overall, both dalbavancin and linezolid were considered to have eradicated at least 85% of the baseline pathogens at these visits. Raad et al., 200538 Table 2 Clinical, Microbiological, and Overall Success with Dalbavancin and Linezolid Clinical Success (%) End-of-therapy visit • Dalbavancin • Linezolid Test-of-cure visit • Dalbavancin • Linezolid 92.3 94.2 88.9 91.2 Microbiological Success (%) 87.5 90.2 89.5 87.5 Overall Success (%)* 87.5 88.4 88.4 86.8 * Overall success = clinical and microbiological success combined. The efficacy of dalbavancin in patients with catheter-related bloodstream infections was compared with vancomycin in a prospective, phase 2, randomized, controlled, open-label trial. The study enrolled participants with signs and symptoms of bacteremia, including fever and chills that were possibly or definitely related to the bloodstream infections. An IV infusion of dalbavancin at a loading dose of 1,000 mg was followed by a 500-mg dose in eight days; the vancomycin dose was 1,000 mg twice daily for 14 days. The primary outcome was efficacy at the TOC assessment, which included clinical and microbiological cures. The secondary outcome was the rate of cure at the end of treatment. At the investigator’s discretion, gram-negative coverage with aztreonam or ceftazidime and anaerobic coverage with metronidazole were added. The catheters were removed in all instances if a catheter-related bloodstream infection was suspected. Sixty-seven patients were analyzed at the end of the study; evaluable results for the TOC visit were presented for 14 dalbavancin patients (42%) and for 20 vancomycin patients (59%). The most common pathogens identified after culture were S. aureus (43%), including MRSA (26%), CNS (48%), and E. faecalis (9%). The microbiologically assessed intentto-treat population at the end of treatment revealed an overall success rate of 91.3% with dalbavancin and 64.3% with vancomycin. At the TOC visit, overall success rates were 87% for dalbavancin and 50% for vancomycin (P < 0.05). At the end of therapy and at the TOC visit, results for the evaluable population of patients revealed similar success rates favoring dalbavancin. SAFETY PROFILE In the phase 1, single-dose and multiple-dose–ranging study by Leighton et al., dalbavancin was well tolerated with no evidence of dose-limiting toxicities.15 The most common adverse effects were pyrexia (50%), headache (25%), and nau- sea (6%). However, patients receiving placebo also reported pyrexia (38%) and headache (31%). No auditory changes were reported among the volunteers. In assessments of the drug’s safety, adverse events probably or possibly related to therapy were reported by 25.4% of the dalbavancin patients and by 32.2% of the linezolid patients.37 These adverse events were generally mild or moderate in intensity and were comparable in both groups (Table 3). Treatment-related adverse effects that were considered serious included mild leukopenia, which resolved spontaneously in the patients who were given dalbavancin, and moderate thrombocytopenia in the linezolidtreated patients. In the comparative trial of catheter-related bloodstream infections by Raad et al. (Table 4), adverse events were relatively mild with both dalbavancin and vancomycin.38 Common adverse effects included hypotension, hypokalemia, diarrhea, constipation, anemia, and fever. Table 3 Adverse Drug Events in a Dose-Ranging Study of Dalbavancin and Linezolid Adverse Event Nausea Diarrhea Headache Abnormal liver function tests Loose stools Thrombocytopenia Fungal vaginosis Elevated alanine aminotransferase Rash Dalbavancin (%) 3.2 2.5 1.9 1.6 0.4 0.2 0.9 1.2 1.8 Linezolid (%) 5.3 5.7 1.8 1.1 2.1 2.5 1.8 1.8 1.8 Data from Jauregui LE, Babazadeh S, Seltzer E, et al. Clin Infect Dis 2005;41:1407–1415.37 continued on page 50 Vol. 33 No. 1 • January 2008 • P&T® 45
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