Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Resistance to Beta-lactamase Inactivation

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1974 Jan 1

PMID 4599124

Citations 54

Authors

H R Onishi

D R DAOUST

S B Zimmerman

D HENDLIN

E O Stapley

Affiliations

Soon will be listed here.

Abstract

Cefoxitin is a new, cephalosporin-like antibiotic which is highly resistant to hydrolysis by beta-lactamase. Ninety-one cultures were selected either for their general resistance to cephalosporin antibiotics or for their ability to produce beta-lactamase. Some of these cultures were resistant to cefoxitin. The capacity of each of the 91 strains to hydrolyze cefoxitin with beta-lactamase was determined. Only seven of the cultures degraded the antibiotic as determined by a general assay for beta-lactamase. Several others were able to hydrolyze cefoxitin after enzyme was induced by low concentrations of the antibiotic. The role of the constitutive and inducible enzyme in bacterial resistance to the antibiotic was investigated. Enzymatic destruction of cefoxitin was found to be an important factor contributing to bacterial resistance. However, the complete and rapid degradation of cefoxitin is not essential to resistance since one strain, Enterobacter cloacae 1316, hydrolyzed the antibiotic very slowly but was able to grow unaffected in the presence of cefoxitin. The presence of the enzyme is not necessarily sufficient to confer resistance since another culture, Klebsiella D535, readily hydrolyzed the antibiotic but was susceptible to it.

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References

Goldner M, Glass D, Fleming P . Spontaneous mutant with loss of beta-lactamase in Aerobacter cloacae. J Bacteriol. 1969; 97(2):961. PMC: 249786. DOI: 10.1128/jb.97.2.961-.1969. View

Neu H . Effect of beta-lactamase location in Escherichia coli on penicillin synergy. Appl Microbiol. 1969; 17(6):783-6. PMC: 377810. DOI: 10.1128/am.17.6.783-786.1969. View

Jack G, Richmond M . A comparative study of eight distinct beta-lactamases synthesized by gram-negative bacteria. J Gen Microbiol. 1970; 61(1):43-61. DOI: 10.1099/00221287-61-1-43. View

Fleming P, Goldner M, Glass D . Observations on the nature, distribution, and significance of cephalosporinase. Lancet. 1963; 1(7296):1399-401. DOI: 10.1016/s0140-6736(63)92051-8. View

KARADY S, Pines S, Weinstock L, Roberts F, Brenner G, Hoinowski A . Semisynthetic cephalosporins via a novel acyl exchange reaction. J Am Chem Soc. 1972; 94(4):1410-1. DOI: 10.1021/ja00759a090. View

GARBER N, Friedman J . Beta-lactamase and the resistance of Pseudomonas aeruginosa to various penicillins and cephalosporins. J Gen Microbiol. 1970; 64(3):343-52. DOI: 10.1099/00221287-64-3-343. View

Sabath L, Jago M, ABRAHAM E . Cephalosporinase and penicillinase activities of a beta-lactamase from Pseudomonas pyocyanea. Biochem J. 1965; 96(3):739-52. PMC: 1207212. DOI: 10.1042/bj0960739. View

BAUER A, KIRBY W, SHERRIS J, Turck M . Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966; 45(4):493-6. View

Hennessey T . Inducible beta-lactamase in Enterobacter. J Gen Microbiol. 1967; 49(2):277-85. DOI: 10.1099/00221287-49-2-277. View

10.

WALLICK H, HENDLIN D . Cefoxitin, a semisynthetic cephamycin antibiotic: susceptibility studies. Antimicrob Agents Chemother. 1974; 5(1):25-32. PMC: 428914. DOI: 10.1128/AAC.5.1.25. View

11.

Sabath L, FINLAND M . Resistance of penicillins and cephalosporins to beta-lactamases from Gram-negative bacilli: some correlations with antibacterial activity. Ann N Y Acad Sci. 1967; 145(2):237-47. DOI: 10.1111/j.1749-6632.1967.tb50222.x. View

12.

DAOUST D, Onishi H, WALLICK H, HENDLIN D, Stapley E . Cephamycins, a new family of beta-lactam antibiotics: antibacterial activity and resistance to beta-lactamase degradation. Antimicrob Agents Chemother. 1973; 3(2):254-61. PMC: 444396. DOI: 10.1128/AAC.3.2.254. View

13.

Farrar W, Krause J . Relationship Between beta-Lactamase Activity and Resistance of Enterobacter to Cephalothin. Infect Immun. 1970; 2(5):610-6. PMC: 416058. DOI: 10.1128/iai.2.5.610-616.1970. View

14.

Novick R . Micro-iodometric assay for penicillinase. Biochem J. 1962; 83:236-40. PMC: 1243538. DOI: 10.1042/bj0830236. View

15.

AYLIFFE G . Cephalosporinase and penicillinase activity of Gram-negative bacteria. J Gen Microbiol. 1965; 40(1):119-26. DOI: 10.1099/00221287-40-1-119. View

16.

Miller A, CELOZZI E, Kong Y, Pelak B, HENDLIN D, Stapley E . Cefoxitin, a semisynthetic cephamycin antibiotic: in vivo evaluation. Antimicrob Agents Chemother. 1974; 5(1):33-7. PMC: 428915. DOI: 10.1128/AAC.5.1.33. View

17.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

18.

Richmond M, Jack G, Sykes R . Mechanisms of drug resistance. The beta-lactamases of gram-negative bacteria including pseudomonads. Ann N Y Acad Sci. 1971; 182:243-57. DOI: 10.1111/j.1749-6632.1971.tb30661.x. View