title: Ceftobiprole medocaril is an effective treatment against methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis in a rat model.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis after median sternotomy is a major complication of cardiac surgery with significant morbidity and mortality rates. We evaluated the efficacy of ceftobiprole medocaril in a new rat model of mediastinitis and compared it to vancomycin. The model was induced in 92 rats. Infection was induced immediately after median sternotomy by the injection of MRSA (strain 3020, 1 × 10(7) cfu/rat) into the sternal bone. After 24 h, rats (groups of 6-8) were treated intraperitoneally for 5 days or 14 days by either: (i) saline (control, q8h), (ii) ceftobiprole medocaril (70 or 100 mg/kg, q8h), or (iii) vancomycin (50 mg/kg, q12h). Efficacy was determined by a reduction in bacterial cfu in the sternum and spleen tissues. Comparisons were performed using the Mann-Whitney test. A 5-day treatment course of ceftobiprole at both doses tested lead to a significant reduction in MRSA load in the sternum (p < 0.01) as compared to the control group and compared to 5-day vancomycin treatment, which lead to a non-significant reduction (p = 0.07). Longer treatment (14 days) with ceftobiprole lead to a complete clearance of MRSA from the sternum, similarly to vancomycin. Ceftobiprole also showed a significant effect on eliminating MRSA dissemination to the spleen compared to saline-treated rats. Ceftobiprole was effective in treating MRSA mediastinitis in the rat model. In the 5-day course, ceftobiprole showed a significant reduction in sternal MRSA counts and was superior to vancomycin. After 14 days, both ceftobiprole and vancomycin showed clearance of MRSA from the sternum in more than 50 % of rats and almost complete clearance in the remainder.
authors.affiliation: Division of Epidemiology & Laboratory for Molecular Epidemiology and Antimicrobials Research, Tel-Aviv Sourasky Medical Center, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Barnea
authors.forename: S
authors.initials: S
authors.lastname: Navon-Venezia
authors.forename: B
authors.initials: B
authors.lastname: Kuzmenko
authors.forename: N
authors.initials: N
authors.lastname: Artzi
authors.forename: Y
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D008480:Mediastinitis / Q000188:drug therapy* / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification*; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013249:Sternum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C505439:ceftobiprole medocaril
references.citation: Thorac Cardiovasc Surg. 1992 Jun;40(3):148-51
references.pmid: 1412382
references.citation: Clin Infect Dis. 2004 Jun 1;38(11):1555-60
references.pmid: 15156442
references.citation: Clin Infect Dis. 2007 Sep 15;45 Suppl 3:S184-90
references.pmid: 17712745
references.citation: Circulation. 1995 Oct 15;92(8):2245-51
references.pmid: 7554208
references.citation: J Clin Microbiol. 2002 Aug;40(8):2936-41
references.pmid: 12149355
references.citation: Ann Thorac Surg. 2000 Dec;70(6):2004-7
references.pmid: 11156110
references.citation: Antimicrob Agents Chemother. 2002 Jan;46(1):171-7
references.pmid: 11751129
references.citation: Clin Infect Dis. 1997 Nov;25(5):1060-4
references.pmid: 9402357
references.citation: Antimicrob Agents Chemother. 2010 Feb;54(2):610-3
references.pmid: 19917746
references.citation: Eur J Cardiothorac Surg. 2000 Feb;17(2):154-60
references.pmid: 10731651
references.citation: Antimicrob Agents Chemother. 2005 Sep;49(9):3789-93
references.pmid: 16127054
references.citation: J Antimicrob Chemother. 2008 Dec;62(6):1339-43
references.pmid: 18799473
references.citation: Curr Opin Pharmacol. 2006 Oct;6(5):480-5
references.pmid: 16899405
references.citation: Circulation. 2003 Jul 8;108(1):73-8
references.pmid: 12821547
references.citation: Infect Control Hosp Epidemiol. 2002 Apr;23(4):177-82
references.pmid: 12002231
references.citation: J Clin Epidemiol. 1999 Dec;52(12):1249-56
references.pmid: 10580789
references.citation: Antimicrob Agents Chemother. 2001 Mar;45(3):825-36
references.pmid: 11181368
references.citation: ANZ J Surg. 2001 Nov;71(11):662-4
references.pmid: 11736828
references.citation: Am J Infect Control. 2002 Dec;30(8):458-75
references.pmid: 12461510
references.citation: Antimicrob Agents Chemother. 2008 May;52(5):1618-22
references.pmid: 18332175
references.citation: Infect Control Hosp Epidemiol. 2004 Jun;25(6):468-71
references.pmid: 15242193
references.citation: Antimicrob Agents Chemother. 2007 Jul;51(7):2621-4
references.pmid: 17470659