A synergistic in vitro bactericidal effect of combinations of chloramphenicol and beta-lactams on strains of Enterobacteriaceae is described. The synergism is seen with strains which are resistant to the beta-lactam and is due to chloramphenicol-induced inhibition of beta-lactamase production.The increasing resistance of gram-negative bacilli to anti-bacterial agents (6), including gentamicin (12) and the cephalosporins (19), raises the possibility of having to resort to a synergistic combination of drugs in the therapy of infections caused by these bacteria.Synergism between chloramphenicol and several beta-lactam antibiotics on strains of Klebsiella-Enterobacter-Serratia, which are resistant to the beta-lactam alone, has recently been described as a not uncommon event (13). The present study was undertaken to examine the occurrence of this synergism with gram-negative bacilli belonging to other genera, and to elucidate its mechanism.MATERIALS AND METHODS Bactericidal effect of combinations of chloramphenicol and three beta-lactams. Ninety-four strains of Enterobacteriaceae isolated in the diagnostic laboratory of the Department of Clinical Microbiology, Hadassah University Hospital, from sputum, infected wounds, stools, and blood cultures were studied. These strains were identified according to Ewing (5) as Escherichia coli (15 strains), Shigella (15 strains), Citrobacter (3 strains), Salmonella (12 strains), Proteus (13 strains), Providence (6 strains), Klebsiella (11 strains), Enterobacter (9 strains), and Serratia (10 strains). The cellophane transfer technique of Chabbert (1) as modified by Cluzel et al. (4) was used to determine a synergistic bactericidal effect. The principles and techniques of this method have recently been described and illustrated in detail (3,7,8,16). The results were interpreted according to previously reported criteria and were classified as synergism, antagonism, or indifference (3,7,8,16). The beta-lactams used were ampicillin, cephaloridine, and carbenicillin.Mechanism of synergistic effect. For these experiments the following strains of beta-lactamase-producing Enterobacteriaceae were used: Enterobacter cloacae NCTC 10005, Klebsiella pneumoniae K 1296 obtained from John Matsen, University of Minnesota (14), and eight strains (see Table 2) isolated from clinical material at the Hadassah University Hospital and identified according to Ewing (5). Each strain was tested for beta-lactamase production by the iodometric method as described by Workman and Farraz (22).Susceptibility to single antibiotics. The susceptibility of these strains to chloramphenicol and cephaloridine was determined by preparing doubling dilutions of the antibiotic in Trypticase soy broth (TSB; Difco). The inoculum was 0.1 ml of a suitably diluted overnight culture in TSB to give a final concentration in the test dilutions of approximately 105 bacteria/ml. The minimal inhibitory concentration (MIC) was expressed in terms of the lowest concentration of antibiotic that totally inhibited visible growth after 24 h...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.