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Journal of the Pediatric Infectious Diseases Society Advance Access published June 2, 2014.

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1 Journal of the Pediatric Infectious Diseases Society Advance Access published June 2, 2014

2 Modes of Antimicrobial Actions مهار سنتز دیواره سلولی مهار سنتز پروتئین صدمه به غشای پلاسمایی مهار سنتز اسیدنوکلئیک مهار سنتز برخی متابولیت های ضروری

3 Inhibition of cell wall synthesis Examples: Beta-lactams, Glycopeptides, Lipopeptides: Daptomycin, Bacitracin. 3

4 Daptomycin (Cubicin) Daptomycin is the first member of a new class of the cyclic lipopeptides. A class of antibiotics with a spectrum of activity similar to that of vancomycin, Daptomycin is highly bactericidal against S. aureus and other G+ bacteria. FDA Approrved drug, Daptomycin is inactivated by surfactant and should NOT be used to treat pneumonia. 4

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6 Introduction

7 Daptomycin is a lipopeptide antibiotic approved in 2003 for the treatment of complicated skin and skin-structure infections in adults. In 2006, an indication was added for S.aureus bacteremia and right-sided endocarditis. Daptomycin can be a useful alternative to first-line agents for infections with MRSA, MSSA, and VRE. Introduction…

8 METHODS Retrospective analysis of daptomycin use in hospitalized US children during a 9-year period was conducted using the Pediatric Health Information System (PHIS) database. All patients <18 years old with at least 1 charge for daptomycin discharged between January 1, 2004 and December 31, 2012.

9 RESULTS During the 9-year study period, 1035 hospitalizations with at least 1 administration of daptomycin occurred in 794 patients (<1 antibiotic-day per 1000 patient-days). Of note, 47.3% of children were younger than 10 years of age. MRSA was identified in 182 (17.6%) hospitalizations Enterococcus spp. were identified in 110 (10.6%) hospitalizations.

10 The most frequent diagnoses and clinical categories

11 Results … 1/3 of the daptomycin use occurred in hospitalizations related to oncology. The median duration of daptomycin therapy was 5 days (range 2–13) Qs: What were… 1.The most common antibiotics with activity against MRSA used for at least 48 hours prior to daptomycin administration? – vancomycin, linezolid, and clindamycin. 2.The most common anti-MRSA antibiotics used for at least 48 hrs in conjunction with daptomycin? – Linezolid, TMP/SMX, and rifampin 3.The most common APR-DRG among children who died during the hospitalization? – BMT (31.3%)

12 Conclusion Daptomycin use was uncommon but increased over time. A minority of hospitals accounted for the majority of use. This variability of daptomycin use highlights the need for future studies to assess the efficacy and safety of daptomycin in children.

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