Pharmacy and Therapeutics - January 2008 - (Page 42) DRUG FORECAST Dalbavancin (Zeven), a Novel Glycopeptide For Resistant Gram-Positive Organisms Jennifer Colabella, PharmD, and Larisa Chagan, PharmD, BCPS INTRODUCTION Severe infections associated with gram-positive organisms such as Staphylococcus aureus contribute to significant morbidity and mortality.1–10 Examples include bacteremia, skin and soft-tissue infections (SSTIs), hospital-acquired pneumonia, endocarditis, meningitis, bone and joint infections, and catheter-related bloodstream infections. The prevalence of antibiotic-resistant nosocomial bloodstream infections is increasing in hospitals in the U.S.11 A 2004 repor t of bloodstream infections reviewed data from the prospective nationwide SCOPE study (Sur veillance and Control of Pathogens of Epidemiological Importance).11 In this study, 24,179 cases of nosocomial bloodstream infections were identified over a period of seven years. Most of these infections were associated with gram-positive organisms, accounting for 65% of all cases. The crude mortality rate (per 1,000 people) was 27%. Among the most common organisms were coagulase-negative staphylococci (CNS) (31%), S. aureus (20%), and enterococci (9%). The prevalence of methicillin-resistant S. aureus (MRSA) increased from 22% in 1995 to Disclosure: The authors have no commercial relationships to disclose. At the time of this writing, Dr. Colabella was a pharmacy student at Saint Vincent Medical Center in New York, New York. She is presently a hospital pharmacist at Stony Brook University Medical Center in Stony Brook, New York. Dr. Chagan is Assistant Professor of Pharmacy Practice at the Arnold & Marie Schwartz College of Pharmacy and Health Sciences at Long Island University and a Clinical Pharmacist in Critical Care at Saint Vincent’s Medical Center in New York. Drug Forecast is a regular column coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York. 57% in 2001 (P < 0.001). Vancomycin-reance and toxicities associated with antisistant enterococci (VRE) were also iden- microbial agents, it is imperative to contified in 2% of Enterococcus faecalis iso- tinue the search for other “magic bullates and in 60% of Enterococcus faecium lets” to control gram-positive pathogens. isolates. Dalbavancin (Zeven, Vicuron/Pfizer), a The emergence of resistance among novel, second-generation glycopeptide, gram-positive organisms such as S. au- is similar to vancomycin and teicoplanin reus and Streptococcus pyogenes is affect- (Targocid, Sanofi-Aventis). It is being ing the current management of SSTIs.12 studied in phase 3 clinical trials for the The empirical choice of antibiotics must treatment of gram-positive infections. include agents with activity against resistant strains as a result of increasing re- PHARMACOLOGY sistance of MRSA in the community.13 It Dalbavancin is a bactericidal, dimethyl is recommended that semisynthetic peniamino-propylamide derivative of the glycillin, a first-generation or second-genercopeptide A40926.14 Glycopeptides inhibation oral cephalosporin, a macrolide, or it the bacterial cell wall by binding to the clindamycin (Cleocin, Pfizer) be used for C terminal of the D-alanyl-D-alanine moiminor SSTIs. However, about 50% of ety of peptidoglycan, and they block enMRSA strains have inducible clinzymes involved in the final steps of pepdamycin resistance. The emergence of tidoglycan synthesis and cell wall community-acquiredMRSA must be con- formation. Osmotic shock, causing cell sidered because treatment failure ratesof rupture, results from the damaged cell 21% have been reported in some patients wall, which cannot maintain the osmotic treated with doxycycline (Vibramycin, gradient between the bacterial cell and Pfizer) or minocycline (Minocin, its environment; consequently, the bacWyeth).12 Therefore, it is recommended teria die. Dalbavancin’s long lipophilic side that patients be re-evaluated in a day or chain is attached to the basic glycopeptwo following a diagnosis. If the infectide backbone (Figure 1). This side chain tion progresses despite therapy with the confirms stabilization and anchors the current regimen, broader coverage for agent, ensuring prolonged interaction resistant organisms should be provided. with peptidoglycan. This increased interA study of adults presenting to emergency departments with SSTIs OH has confirmed the increasing H N OH prev alence and resistance of O MRSA in the community.13 In this O O CO H O O study, S. aureus was isolated in H HO 320 (76%) of SSTIs. The prevaCl O O HO lence of MRSA was 59% (range, H H H H HH O N N N N N N 15%–74%.) H H H H H O O H NH The currently available options O Cl to treat resistant gram-positive inNH OH HO fections include vancomycin (VanHO O O OH OH cocin, ViroPharma), linezolid N O (Zyvox, Pfizer), quinupristin– dalOH fopristin (Synercid, Monarch), OH OH daptomycin (Cubicin, Cubist), Figure 1 Chemical structure of dalbavancin. and tigecycline (Tygacil, Wyeth). In light of the developing resist2 42 P&T® • January 2008 • Vol. 33 No. 1
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