Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Sep;35(9):1824–1828. doi: 10.1128/aac.35.9.1824

Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria.

R H Eng 1, F T Padberg 1, S M Smith 1, E N Tan 1, C E Cherubin 1
PMCID: PMC245275  PMID: 1952852

Abstract

Antimicrobial agents are most often tested against bacteria in the log phase of multiplication to produce the maximum bactericidal effect. In an infection, bacteria may multiply less optimally. We examined the effects of several classes of antimicrobial agents to determine their actions on gram-positive and gram-negative bacteria during nongrowing and slowly growing phases. Only ciprofloxacin and ofloxacin exhibited bactericidal activity against nongrowing gram-negative bacteria, and no antibiotics were bactericidal (3-order-of-magnitude killing) against Staphylococcus aureus. For the very slowly growing gram-negative bacteria studied, gentamicin (an aminoglycoside), imipenem (a carbapenem), meropenem (a carbapenem), ciprofloxacin (a fluoroquinolone), and ofloxacin (a fluoroquinolone) exhibited up to 5.7 orders of magnitude more killing than piperacillin or cefotaxime. This is in contrast to optimally growing bacteria, in which a wide variety of antibiotic classes produced 99.9% killing. For the gram-positive and gram-negative bacteria we examined, antibiotic killing was greatly dependent on the growth rate. The clinical implications of slow killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are unknown.

Full text

PDF
1824

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boon R. J., Beale A. S. Response of Streptococcus pyogenes to therapy with amoxicillin or amoxicillin-clavulanic acid in a mouse model of mixed infection caused by Staphylococcus aureus and Streptococcus pyogenes. Antimicrob Agents Chemother. 1987 Aug;31(8):1204–1209. doi: 10.1128/aac.31.8.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown M. R., Allison D. G., Gilbert P. Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? J Antimicrob Chemother. 1988 Dec;22(6):777–780. doi: 10.1093/jac/22.6.777. [DOI] [PubMed] [Google Scholar]
  3. Cherubin C. E., Eng R. H. Experience with the use of cefotaxime in the treatment of bacterial meningitis. Am J Med. 1986 Mar;80(3):398–404. doi: 10.1016/0002-9343(86)90713-8. [DOI] [PubMed] [Google Scholar]
  4. Chuard C., Lucet J. C., Rohner P., Herrmann M., Auckenthaler R., Waldvogel F. A., Lew D. P. Resistance of Staphylococcus aureus recovered from infected foreign body in vivo to killing by antimicrobials. J Infect Dis. 1991 Jun;163(6):1369–1373. [PubMed] [Google Scholar]
  5. Cozens R. M., Markiewicz Z., Tuomanen E. Role of autolysins in the activities of imipenem and CGP 31608, a novel penem, against slowly growing bacteria. Antimicrob Agents Chemother. 1989 Oct;33(10):1819–1821. doi: 10.1128/aac.33.10.1819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cozens R. M., Tuomanen E., Tosch W., Zak O., Suter J., Tomasz A. Evaluation of the bactericidal activity of beta-lactam antibiotics on slowly growing bacteria cultured in the chemostat. Antimicrob Agents Chemother. 1986 May;29(5):797–802. doi: 10.1128/aac.29.5.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eng R. H., Cherubin C. E., Pechere J. C., Beam T. R., Jr Treatment failures of cefotaxime and latamoxef in meningitis caused by Enterobacter and Serratia spp. J Antimicrob Chemother. 1987 Dec;20(6):903–911. doi: 10.1093/jac/20.6.903. [DOI] [PubMed] [Google Scholar]
  8. Eng R. H., Smith S. M., Cherubin C. E., Tan E. N. Evaluation of two methods for overcoming the antibiotic carry-over effect. Eur J Clin Microbiol Infect Dis. 1991 Jan;10(1):34–38. doi: 10.1007/BF01967095. [DOI] [PubMed] [Google Scholar]
  9. Evans R. C., Holmes C. J. Effect of vancomycin hydrochloride on Staphylococcus epidermidis biofilm associated with silicone elastomer. Antimicrob Agents Chemother. 1987 Jun;31(6):889–894. doi: 10.1128/aac.31.6.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Smith S. M., Eng R. H. Activity of ciprofloxacin against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1985 May;27(5):688–691. doi: 10.1128/aac.27.5.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tuomanen E. Phenotypic tolerance: the search for beta-lactam antibiotics that kill nongrowing bacteria. Rev Infect Dis. 1986 Jul-Aug;8 (Suppl 3):S279–S291. doi: 10.1093/clinids/8.supplement_3.s279. [DOI] [PubMed] [Google Scholar]
  12. Widmer A. F., Frei R., Rajacic Z., Zimmerli W. Correlation between in vivo and in vitro efficacy of antimicrobial agents against foreign body infections. J Infect Dis. 1990 Jul;162(1):96–102. doi: 10.1093/infdis/162.1.96. [DOI] [PubMed] [Google Scholar]
  13. Wu P. J., Livermore D. M. Response of chemostat cultures of Pseudomonas aeruginosa to carbapenems and other beta-lactams. J Antimicrob Chemother. 1990 Jun;25(6):891–902. doi: 10.1093/jac/25.6.891. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES