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Journal of Antimicrobial Chemotherapy (1986) 18, 239-250
© 1986 The British Society for Antimicrobial Chemotherapy

research-article

Enhanced bactericidal action of mouse macrophages by subinhibitory concentrations of monobactams

Kyoko Iida-Tanaka, Terukazu Tanaka, Shozo Irino and Ariaki Nagayama*

1st Department of Internal Medicine, Kagawa Medical School Miki, Kagawa, 761-07 *Department of Microbiology, Saga Medical School Nabeshima, Saga, 840-01, Japan

accepted 4 February 1986

The effects of sub-minimum inhibitory concentrations (sub-MICs) of monobactams (aztreonam and AMA1080) on the host-parasite relationship were studied in an invitro system using an established mouse macrophage cell line. The presence of subMICs aztreonam or AMA1080 enhanced significantly the macrophage bactericidal activity against Escherichia coli S615, Pseudomonas aeruginosa K1, Klebsiella pneumoniae 12 and Serratia marcescens US5. Even four times the MIC of monobactams had no direct effect on macrophages. A synergistic bactericidal effect against E. coli was also observed with sub-MICs of monobactams and lysozyme or macrophage lysate. Furthermore, E. coli treated with sub-MICs of aztreonam was more sensitive to two bactericidal macrophage products, hydrogen peroxide and superoxide anion. These results suggest that the effects of monobactams are exerted on bacteria and not on macrophages; sub-inhibitory levels of monobactams may alter the bacterial cell rendering it more susceptible to bactericidal substances released by macrophages, thus favouring phagocytosis and killing by macrophages. Electron microscopic observations support these conclusions. This study provides evidence that monobactams at sub-MICs may work in partnership with host defences against Gram-negative bacterial infections.


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