Abstract
An isogenic set of mutants of Pseudomonas aeruginosa, altered in permeability or permeability plus constitutive production of beta-lactamase, was examined for susceptibility to newer beta-lactam antibiotics. Kinetic data on the chromosomal beta-lactamase and susceptibility studies for the test beta-lactams indicate that permeability was the major mechanism of resistance to the poorly hydrolyzed and nonhydrolyzed antibiotics, e.g., carbenicillin, moxalactam, and cefsulodin. An exception was cefotaxime, with a low Km and a low Vmax, which had reduced efficacy in the permeability mutant and was further affected by the constitutive beta-lactamase. In this case, since the Vmax was low, a nonhydrolytic barrier may provide the additional reduction in susceptibility.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beckwith D. G., Jahre J. A. Role of a cefoxitin-inducible beta-lactamase in a case of breakthrough bacteremia. J Clin Microbiol. 1980 Oct;12(4):517–520. doi: 10.1128/jcm.12.4.517-520.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bryan L. E., Kwan S., Godfrey A. J. Resistance of Pseudomonas aeruginosa mutants with altered control of chromosomal beta-lactamase to piperacillin, ceftazidime, and cefsulodin. Antimicrob Agents Chemother. 1984 Mar;25(3):382–384. doi: 10.1128/aac.25.3.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Darveau R. P., Hancock R. E. Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J Bacteriol. 1983 Aug;155(2):831–838. doi: 10.1128/jb.155.2.831-838.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillett A. P. Antibiotics against Pseudomonas. J Antimicrob Chemother. 1982 Feb;9 (Suppl B):41–48. doi: 10.1093/jac/9.suppl_b.41. [DOI] [PubMed] [Google Scholar]
- Godfrey A. J., Bryan L. E. Mutation of Pseudomonas aeruginosa specifying reduced affinity for penicillin G. Antimicrob Agents Chemother. 1982 Feb;21(2):216–223. doi: 10.1128/aac.21.2.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godfrey A. J., Bryan L. E., Rabin H. R. beta-Lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment. Antimicrob Agents Chemother. 1981 May;19(5):705–711. doi: 10.1128/aac.19.5.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godfrey A. J., Hatlelid L., Bryan L. E. Correlation between lipopolysaccharide structure and permeability resistance in beta-lactam-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984 Aug;26(2):181–186. doi: 10.1128/aac.26.2.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gootz T. D., Sanders C. C., Goering R. V. Resistance to cefamandole: derepression of beta-lactamases by cefoxitin and mutation in Enterobacter cloacae. J Infect Dis. 1982 Jul;146(1):34–42. doi: 10.1093/infdis/146.1.34. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Leive L. The barrier function of the gram-negative envelope. Ann N Y Acad Sci. 1974 May 10;235(0):109–129. doi: 10.1111/j.1749-6632.1974.tb43261.x. [DOI] [PubMed] [Google Scholar]
- Nicas T. I., Hancock R. E. Pseudomonas aeruginosa outer membrane permeability: isolation of a porin protein F-deficient mutant. J Bacteriol. 1983 Jan;153(1):281–285. doi: 10.1128/jb.153.1.281-285.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikaido H., Nakae T. The outer membrane of Gram-negative bacteria. Adv Microb Physiol. 1979;20:163–250. doi: 10.1016/s0065-2911(08)60208-8. [DOI] [PubMed] [Google Scholar]
- O'Callaghan C. H., Muggleton P. W., Ross G. W. Effects of beta-lactamase from gram-negative organisms on cephalosporins and penicillins. Antimicrob Agents Chemother (Bethesda) 1968;8:57–63. [PubMed] [Google Scholar]
- Preheim L. C., Penn R. G., Sanders C. C., Goering R. V., Giger D. K. Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 1982 Dec;22(6):1037–1041. doi: 10.1128/aac.22.6.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richmond M. H., Sykes R. B. The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol. 1973;9:31–88. doi: 10.1016/s0065-2911(08)60376-8. [DOI] [PubMed] [Google Scholar]
- Ross G. W., O'Callaghan C. H. Beta-lactamase assays. Methods Enzymol. 1975;43:69–85. doi: 10.1016/0076-6879(75)43081-6. [DOI] [PubMed] [Google Scholar]
- Sanders C. C. Novel resistance selected by the new expanded-spectrum cephalosporins: a concern. J Infect Dis. 1983 Mar;147(3):585–589. doi: 10.1093/infdis/147.3.585. [DOI] [PubMed] [Google Scholar]
- Sanders C. C., Sanders W. E., Jr Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future. Rev Infect Dis. 1983 Jul-Aug;5(4):639–648. doi: 10.1093/clinids/5.4.639. [DOI] [PubMed] [Google Scholar]
- Sanders C. C., Sanders W. E., Jr, Goering R. V. In vitro antagonism of beta-lactam antibiotics by cefoxitin. Antimicrob Agents Chemother. 1982 Jun;21(6):968–975. doi: 10.1128/aac.21.6.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Then R. L., Angehrn P. Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism. Antimicrob Agents Chemother. 1982 May;21(5):711–717. doi: 10.1128/aac.21.5.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- VOGEL H. J., BONNER D. M. Acetylornithinase of Escherichia coli: partial purification and some properties. J Biol Chem. 1956 Jan;218(1):97–106. [PubMed] [Google Scholar]
- Yoshimura F., Nikaido H. Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes. J Bacteriol. 1982 Nov;152(2):636–642. doi: 10.1128/jb.152.2.636-642.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmermann W. Penetration of beta-lactam antibiotics into their target enzymes in Pseudomonas aeruginosa: comparison of a highly sensitive mutant with its parent strain. Antimicrob Agents Chemother. 1980 Jul;18(1):94–100. doi: 10.1128/aac.18.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmermann W., Rosselet A. Function of the outer membrane of Escherichia coli as a permeability barrier to beta-lactam antibiotics. Antimicrob Agents Chemother. 1977 Sep;12(3):368–372. doi: 10.1128/aac.12.3.368. [DOI] [PMC free article] [PubMed] [Google Scholar]