Comparative in vitro activity of apalcillin alone and combined with Ro 48-1220, a novel penam beta-lactamase inhibitor.
OBJECTIVE: The in vitro activity of apalcillin plus Ro 48-1220, a novel penam sulfone beta-lactamase inhibitor, was compared with apalcillin alone, piperacillin/tazobactam, ticarcillin/clavulanic acid, amoxicillin/clavulanic acid, imipenem, ceftazidime and cefepime. METHODS: Agar dilution and broth microdilution testing of 854 bacterial strains, subcultured from frozen stocks incubated for 24 h in 5% carbon dioxide, was carried out to determine the minimum bactericidal (MBC) and minimum inhibitory concentrations (MIC) of each of the study drugs in accordance with the NCCLS M26-T method. RESULTS: Apalcillin/Ro 48-1220 was active against all gram-negative aerobic and anaerobic isolates except Klebsiella oxytoca (MIC90 32 microg/mL). Among the Enterobacteriaceae, synergy for apalcillin/Ro 48-1220 (4 microg/mL fixed concentration) vs apalcillin alone was demonstrated for nearly all species when comparing MIC90 results. Apalcillin/Ro 48-1220 was highly potent against beta-lactamase-producing Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae (MICs less-than-or-equal 1 microg/mL). However, much of this activity was due to the direct antimicrobial action of Ro 48-1220 alone (MICs less-than-or-equal 4 microg/mL). All Pseudomonas aeruginosa, Stenotrophomonas (Xanthomonas) maltophilia and Acinetobacter species were inhibited by apalcillin/Ro 48-1220 (MIC90 0.25 to 4 microg/mL). For the aerobic gram-positive organisms, none of the drugs tested were consistently effective against oxacillin-resistant staphylococci, Corynebacterium jeikeium and Enterococcus species other than E. faecalis. Apalcillin/Ro 48-1220 was as effective as piperacillin/tazobactam against Escherichia coli producing extended-spectrum TEM enzymes, but less active against isolates producing SHV-type beta-lactamases. When tested against 204 ceftazidime-, gentamicin- or fluoroquinolone-resistant organisms, 78%, 91% and 66% of strains, respectively, were susceptible to apalcillin/Ro 48-1220 (less-than-or-equal 16 microg/mL). CONCLUSIONS: Apalcillin/Ro 48-1220 is bactericidal with a modest inoculum effect; its wide spectrum of activity favors continued studies of spectrum, pharmacokinetics and in vivo efficacy.
Jones
Ronald N.
RN
Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa.
Johnson
David M.
DM