Pharmacodynamic Activity of Ceftobiprole Compared with Vancomycin versus Methicillin-Resistant \u3cem\u3eStaphylococcus aureus\u3c/em\u3e (MRSA), Vancomycin-Intermediate \u3cem\u3eStaphylococcus aureus\u3c/em\u3e (VISA) and Vancomycin-Resistant \u3cem\u3eStaphylococcus aureus\u3c/em\u3e (VRSA) Using an In Vitro Model

Background This study compared the pharmacodynamics of ceftobiprole and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) using an in vitro model. Methods Two methicillin-susceptible S. aureus (MSSA), two community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 × 106 cfu/mL and ceftobiprole dosed every 8 h (at 0, 8 and 16 h) to simulate the fCmax and t1/2 obtained after 500 mg intravenous (iv) every 8 h dosing (fCmax, 30 mg/L; t1/2, 3.5 h). Vancomycin was dosed every 12 h (at 0 and 12 h) to simulate fCmax and t1/2 obtained after 1 g iv every 12 h dosing (fCmax, 20 mg/L; t1/2, 8 h). Samples were collected over 24 h to assess viable growth. Results Ceftobiprole T \u3e MIC of ≥100% (ceftobiprole MICs, ≤2 mg/L) was bactericidal (≥3 log10 killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin fAUC24/MIC of 340 (vancomycin MIC, 1 mg/L for MSSA and MRSA) resulted in a 1.8–2.6 log10 reduction in colony count at 24 h. Vancomycin fAUC24/MIC of 85–170 (vancomycin MIC, 2–4 mg/L for VISA) resulted in a 0.4–0.7 log10 reduction at 24 h. Vancomycin fAUC24/MIC of 5.3 (vancomycin MIC, 64 mg/L for VRSA) resulted in a limited effect. Conclusions Ceftobiprole T \u3e MIC of ≥100% (ceftobiprole MICs, ≤2 mg/L) was bactericidal (≥3 log10 killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin was bacteriostatic against MSSA, MRSA and VISA, while demonstrating no activity against VRSA

Institutional Experience with Voriconazole Compared with Liposomal Amphotericin B as Empiric Therapy for Febrile Neutropenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90034/1/phco.27.7.970.pd

Analysis of multidrug resistance in the predominant Streptococcus pneumoniae serotypes in Canada:the SAVE study, 2011-15

Objectives: This study assessed MDR invasive isolates of Streptococcus pneumoniae, in relation to serotype evolution in Canada between 2011 and 2015 as part of the annual SAVE study. Methods: As part of a collaboration between the Canadian Antimicrobial Resistance Alliance and Public Health Agency of Canada-National Microbiology Laboratory, 6207 invasive isolates of S. pneumoniae were evaluated. All isolates were serotyped and had antimicrobial susceptibility testing performed, in accordance with CLSI guidelines (M07-A10, 2015). Complete susceptibility profiles were available for 6001 isolates. MDR was defined as resistance to three or more classes of antimicrobial agents (with penicillin MIC ≥2 mg/L defined as resistant). Results: The overall rate of MDR S. pneumoniae was 6.2% (372/6001) in SAVE, decreasing significantly from 8.5% in 2011 to 5.6% in 2015 (P = 0.0041). MDR was observed in 32 serotypes, with serotypes 15A and 19A predominating (26.6% and 41.7% of the MDR isolates, respectively). The overall proportion of serotypes 19A, 7F and 33A decreased significantly (P 5%) for 24F and 33F. Conclusions: In 2015, 56.3% of invasive MDR S. pneumoniae were serotypes included in the PCV-13 vaccine. PCV-13 includes the most commonly identified serotype, 19A; however, other increasingly important MDR serotypes, such as 15A, 24F and 33F, are notably not in the currently used vaccines

Molecular Epidemiology of Penicillin-Resistant and Ciprofloxacin-Resistant Streptococcus pneumoniae in Canada

Eighty-nine penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae isolates were evaluated by serotyping and pulsed-field gel electrophoresis. Although penicillin-resistant isolates demonstrated considerable homogeneity, resistance to ciprofloxacin did not correlate with a reduction in genotypic variability. These results suggest that, unlike that of penicillin resistance, the spread of S. pneumoniae ciprofloxacin resistance in Canada is currently not attributable to clonal dissemination