title: Comparative in vitro activity of ceftaroline, ceftaroline-avibactam, and other antimicrobial agents against aerobic and anaerobic bacteria cultured from infected diabetic foot wounds.
abstract: Foot infections are the most common infectious complication of diabetes. Moderate to severe diabetic foot infections (DFI) are typically polymicrobial with both aerobic and anaerobic organisms. The role of MRSA in these wounds has become an increasing concern. To determine if the addition of avibactam, a novel non-beta-lactam beta-lactamase inhibitor, to ceftaroline would be more active than ceftaroline alone, we tested 316 aerobic pathogens and 154 anaerobic recovered from patients with moderate to severe DFI, and compared ceftaroline with and without avibactam to other agents. Testing on aerobes was done by broth microdilution and by agar dilution for anaerobes, according to CLSI M11-A8, and M7-A8 standards. Ceftaroline-avibactam MIC90 for all Staphylococcus spp. including MRSA was 0.5 μg/mL, and for enterococci was 1 μg/mL. The MIC90s for enteric Gram-negative rods was 0.125 μg/mL. The addition of avibactam to ceftaroline reduced the ceftaroline MICs for 2 strains of resistant Enterobacter spp. and for 1 strain of Morganella. Against anaerobic Gram-positive cocci ceftaroline-avibactam had an MIC90 0.125 μg/mL and for clostridia 1 μg/mL. Avibactam improved ceftaroline's MIC90s for Bacteroides fragilis from >32 to 2 μg/mL and for Prevotella spp. from >32 to 1 μg/mL. Ceftaroline alone demonstrates excellent in vitro activity against most of the aerobes found in moderate to severe DFI. The addition of avibactam provides an increased spectrum of activity including the beta-lactamase producing Prevotella, Bacteroides fragilis and ceftaroline resistant gram-negative enteric organisms.
authors.affiliation: R. M. Alden Research Laboratory, Culver City, CA 90230, USA. ejcgmd@aol.com
authors.forename: Ellie J C
authors.initials: EJ
authors.lastname: Goldstein
authors.forename: Diane M
authors.initials: DM
authors.lastname: Citron
authors.forename: C Vreni
authors.initials: CV
authors.lastname: Merriam
authors.forename: Kerin L
authors.initials: KL
authors.lastname: Tyrrell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001420:Bacteria, Aerobic / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001441:Bacteroides fragilis / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology*; D048909:Diabetes Complications / Q000382:microbiology*; D004357:Drug Synergism; D004754:Enterobacter / Q000187:drug effects; D005534:Foot Diseases / Q000382:microbiology*; D006801:Humans; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D020596:Morganella / Q000187:drug effects; D018720:Prevotella / Q000187:drug effects; D018440:beta-Lactam Resistance; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D002511:Cephalosporins; D000097583:Ceftaroline; C543519:avibactam