title: Use of ceftaroline after glycopeptide failure to eradicate meticillin-resistant Staphylococcus aureus bacteraemia with elevated vancomycin minimum inhibitory concentrations.
abstract: Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2-4 μg/mL). This multicentre, retrospective, case-control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3-15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3-7.5 days) vs. 8 days (IQR, 5.8-19.5 days); P=0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P=0.06) and 6% vs. 38% (P=0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.
authors.affiliation: University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA; Erie County Medical Center, 462 Grider St., Buffalo, NY 14215, USA. Electronic address: paladino@buffalo.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Paladino
authors.affiliation: University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Jacobs
authors.affiliation: University of Pittsburgh, Department of Medicine, 3601 Fifth Ave., Falk Medical Building, Suite 3A, Pittsburgh, PA 15213, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.affiliation: Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Jerusha
authors.initials: J
authors.lastname: Taylor
authors.affiliation: University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Bader
authors.affiliation: CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Adelman
authors.affiliation: CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Wilton
authors.affiliation: Erie County Medical Center, 462 Grider St., Buffalo, NY 14215, USA; University at Buffalo School of Medicine, 326 Biomedical Research Building, 3435 Main St., Buffalo, NY 14214, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Crane
authors.affiliation: University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 213 Kapoor Hall, Buffalo, NY 14214, USA; CPL Associates, LLC, 73 High St., Buffalo, NY 14203, USA.
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Schentag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D016022:Case-Control Studies; D002511:Cephalosporins / Q000627:therapeutic use*; D003710:Demography; D060740:Disease Eradication; D005260:Female; D006020:Glycopeptides / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D013997:Time Factors; D017211:Treatment Failure; D014640:Vancomycin / Q000627:therapeutic use*; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D006020:Glycopeptides; D014640:Vancomycin; D000097583:Ceftaroline
keywords: Ceftaroline fosamil; MRSA bacteraemia; Vancomycin