Abstract
We compared the inoculum effects of 105 recent clinical isolates of the family Enterobacteriaceae on cefoxitin, other cephalosporins, aztreonam, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Piperacillin and aztreonam showed the largest inoculum effect, and cefoxitin showed the smallest. The other cephalosporins tested (cefotetan, ceftizoxime, and ceftriaxone) showed an intermediate inoculum effect. In general, the inoculum effect was of greater magnitude for the penicillin and beta-lactamase inhibitor combinations than for the cephalosporins tested. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. MICs correlated with bactericidal activity at an inoculum level of 10(5) CFU/ml, while activity at 10(8) CFU/ml was variable. Cefoxitin demonstrated the least filamentous transformation and the most rapid bactericidal activity. Aztreonam showed the most marked filamentous transformation and was no longer bactericidal at 10(8) CFU/ml. The beta-lactamase inhibitor combinations showed variable bactericidal activity, and regrowth occurred with a number of strains with all three agents tested.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aldridge K. E., Sanders C. V., Marier R. L. Variation in the potentiation of beta-lactam antibiotic activity by clavulanic acid and sulbactam against multiply antibiotic-resistant bacteria. J Antimicrob Chemother. 1986 Apr;17(4):463–469. doi: 10.1093/jac/17.4.463. [DOI] [PubMed] [Google Scholar]
- Brook I. Inoculum effect. Rev Infect Dis. 1989 May-Jun;11(3):361–368. doi: 10.1093/clinids/11.3.361. [DOI] [PubMed] [Google Scholar]
- Bush K., Freudenberger J. S., Sykes R. B. Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria. Antimicrob Agents Chemother. 1982 Sep;22(3):414–420. doi: 10.1128/aac.22.3.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chapman S. W., Steigbigel R. T. Staphylococcal beta-lactamase and efficacy of beta-lactam antibiotics: in vitro and in vivo evaluation. J Infect Dis. 1983 Jun;147(6):1078–1089. doi: 10.1093/infdis/147.6.1078. [DOI] [PubMed] [Google Scholar]
- Corrado M. L., Landesman S. H., Cherubin C. E. Influence of inoculum size on activity of cefoperazone, cefotaxime, moxalactam, piperacillin, and N-formimidoyl thienamycin (MK0787) against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1980 Dec;18(6):893–896. doi: 10.1128/aac.18.6.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eng R. H., Cherubin C., Smith S. M., Buccini F. Inoculum effect of beta-lactam antibiotics on Enterobacteriaceae. Antimicrob Agents Chemother. 1985 Nov;28(5):601–606. doi: 10.1128/aac.28.5.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eng R. H., Smith S. M., Cherubin C. Inoculum effect of new beta-lactam antibiotics on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984 Jul;26(1):42–47. doi: 10.1128/aac.26.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- French G., Ling T. Amoxycillin/clavulanate resistant Escherichia coli. Lancet. 1988 Mar 26;1(8587):704–704. doi: 10.1016/s0140-6736(88)91500-0. [DOI] [PubMed] [Google Scholar]
- Gisby J., Beale A. S. Comparative efficacies of amoxicillin-clavulanic acid and ampicillin-sulbactam against experimental Bacteroides fragilis-Escherichia coli mixed infections. Antimicrob Agents Chemother. 1988 Dec;32(12):1830–1833. doi: 10.1128/aac.32.12.1830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein E. J., Citron D. M., Corrado M. L. Effect of inoculum size on in vitro activity of norfloxacin against fecal anaerobic bacteria. Rationale for selective decontamination of the digestive tract. Am J Med. 1987 Jun 26;82(6B):84–87. doi: 10.1016/0002-9343(87)90625-5. [DOI] [PubMed] [Google Scholar]
- Jacobus N. V., Cuchural G. J., Jr, Tally F. P. In-vitro susceptibility of the Bacteroides fragilis group and the inoculum effect of newer beta-lactam antibiotics on this group of organisms. J Antimicrob Chemother. 1989 Nov;24(5):675–682. doi: 10.1093/jac/24.5.675. [DOI] [PubMed] [Google Scholar]
- Martinez J. L., Vicente M. F., Delgado-Iribarren A., Perez-Diaz J. C., Baquero F. Small plasmids are involved in amoxicillin-clavulanate resistance in Escherichia coli. Antimicrob Agents Chemother. 1989 Apr;33(4):595–595. doi: 10.1128/aac.33.4.595-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richmond M. H. The beta-lactamase stability of a novel beta-lactam antibiotic containing a 7 alpha-methoxyoxacephem nucleus. J Antimicrob Chemother. 1980 Jul;6(4):445–453. doi: 10.1093/jac/6.4.445. [DOI] [PubMed] [Google Scholar]
- Sabath L. D., Garner C., Wilcox C., Finland M. Effect of inoculum and of beta-lactamase on the anti-staphylococcal activity of thirteen penicillins and cephalosporins. Antimicrob Agents Chemother. 1975 Sep;8(3):344–349. doi: 10.1128/aac.8.3.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanders C. C., Iaconis J. P., Bodey G. P., Samonis G. Resistance to ticarcillin-potassium clavulanate among clinical isolates of the family Enterobacteriaceae: role of PSE-1 beta-lactamase and high levels of TEM-1 and SHV-1 and problems with false susceptibility in disk diffusion tests. Antimicrob Agents Chemother. 1988 Sep;32(9):1365–1369. doi: 10.1128/aac.32.9.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soriano F., Ponte C., Santamaría M., Jimenez-Arriero M. Relevance of the inoculum effect of antibiotics in the outcome of experimental infections caused by Escherichia coli. J Antimicrob Chemother. 1990 Apr;25(4):621–627. doi: 10.1093/jac/25.4.621. [DOI] [PubMed] [Google Scholar]
- Soriano F., Santamaría M., Ponte C., Castilla C., Fernández-Roblas R. In vivo significance of the inoculum effect of antibiotics on Escherichia coli. Eur J Clin Microbiol Infect Dis. 1988 Jun;7(3):410–412. doi: 10.1007/BF01962350. [DOI] [PubMed] [Google Scholar]
- Thomson K. S., Weber D. A., Sanders C. C., Sanders W. E., Jr Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations. Antimicrob Agents Chemother. 1990 Apr;34(4):622–627. doi: 10.1128/aac.34.4.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
