Influence of clindamycin on derepression of β-lactamases in Enterobacter spp. and Pseudomonas aeruginosa

C. C. Sanders, W. E. Sanders, Richard V. Goering

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Abstract

Previous studies in this and other laboratories have shown that derepression of β-lactamases in strains of Enterobacter and Pseudomonas spp. is responsible for the rapid development of resistance to a variety of β-lactam antibiotics. The purpose of the current study was to evaluate the effects of clindamycin on derepression of β-lactamase in these two genera. In tests with four strains of each genus, clindamycin diminished derepression in one isolate of each genus and completely prevented derepression in a second Enterobacter isolate (strain 55). Additional tests with strain 55 revealed that other inhibitors of macromolecular synthesis did not completely prevent derepression of β-lactamase when tested at concentrations that did not inhibit replication. However, clindamycin did not affect synthesis of β-lactamase that was constitutively produced in a mutant of this strain (55M). It also did not inhibit derepression of β-galactosidase in either strain 55 or 55M. Clindamycin did not diminish the bactericidal effects of β-lactam antibiotics aganst Enterobacter or Pseudomonas spp. However, it enhanced the bactericidal activity of cefamandole against strain 55. These in vitro effects of clindamycin on strain 55 that were related to prevention of derepression of β-lactamase were confirmed in vivo with an animal model of infection. These results indicate that in some strains, clindamycin can specifically prevent derepression of β-lactamases without inhibiting growth. Such a selective effect may provide a new approach for the enhancement of the antibacterial activity of certain β-lactam antibiotics.

Original languageEnglish
Pages (from-to)48-53
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume24
Issue number1
StatePublished - 1983

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Enterobacter
Clindamycin
Pseudomonas aeruginosa
Lactams
Anti-Bacterial Agents
Pseudomonas
Galactosidases
Cefamandole
Animal Models
Growth
Infection

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

Influence of clindamycin on derepression of β-lactamases in Enterobacter spp. and Pseudomonas aeruginosa. / Sanders, C. C.; Sanders, W. E.; Goering, Richard V.

In: Antimicrobial Agents and Chemotherapy, Vol. 24, No. 1, 1983, p. 48-53.

Research output: Contribution to journalArticle

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