Comparative in vitro activity of apalcillin alone and combined with Ro 48–1220, a novel penam β‐lactamase inhibitor

Abstract

Objective: The in vitro activity of apalcillin plus Ro 48–1220, a novel penam sulfone β‐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 μg/mL). Among the Enterobacteriaceae, synergy for apalcillin/Ro 48–1220 (4 μg/mL fixed concentration) vs apalcillin alone was demonstrated for nearly all species when comparing MIC90 results. Apalcillin/Ro 48–1220 was highly potent against β‐lactamase‐producing Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae (MICs 1 μg/mL). However, much of this activity was due to the direct antimicrobial action of Ro 48–1220 alone (MICs 4 μg/mL). All Pseudomonas aeruginosa, Stenotrophomonas (Xanthomonas) maltophilia and Acinetobacter species were inhibited by apalcillin/Ro 48–1220 (MIC90 0.25 to 4 μg/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 β‐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 (16 μg/mL). Conclusions: Apalcillin/Ro 48–1220 is bactericidal with a modest inoculum effect; its wice spectrum of activity favors continued studies of spectrum, pharmacokinetics and in vivo efficacy. 1995 European Society of Clinical Microbiology and Infectious Diseases