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. 1997 Nov;41(11):2522–2526. doi: 10.1128/aac.41.11.2522

Studies of the killing kinetics of benzylpenicillin, cefuroxime, azithromycin, and sparfloxacin on bacteria in the postantibiotic phase.

I Odenholt 1, E Löwdin 1, O Cars 1
PMCID: PMC164155  PMID: 9371360

Abstract

Most antibiotics are known to be incapable of killing nongrowing or slowly growing bacteria with few exceptions. Bacterial cell division is inhibited during the postantibiotic phase (PA phase) after short exposure to antibiotics. Only scarce and conflicting data are available concerning the ability of antibiotics to kill bacteria in the PA phase. The aim of the present study was to investigate the killing effect of four different antibiotics on bacteria in the PA phase. A postantibiotic effect (PAE) was induced by exposing Streptococcus pyogenes and Haemophilus influenzae to 10x MICs of benzylpenicillin, cefuroxime, sparfloxacin, and azithromycin. The bacteria were thereafter reexposed to a 10x MIC of the same antibiotic used for the induction of the PAE at the beginning of and after 2 and 4 h in the PA phase. Due to a very long PAE, the bacteria in PA phase induced by azithromycin were also exposed to 10x MICs after 6 and 8 h. A previously unexposed culture exposed to a 10x MIC was used as a control. The results seem to be dependent on both the antibiotic used and the bacterial species. The antibiotics exhibiting a fork bactericidal action gave significantly reduced killing of the bacteria in PA phase (cefuroxime with S. pyogenes, P < 0.01, and sparfloxacin with H. influenzae, P < 0.001), which was restored at 4 h for cefuroxime with S. pyogenes. There was a tendency to restoration of the bactericidal activity also with sparfloxacin and H. influenzae, but there was still a significant difference in killing between the control and the test bacteria in PA phase at 4 h. However, in the combinations with a lesser bactericidal effect (benzylpenicillin with S. pyogenes and sparfloxacin with S. pyogenes), there was no difference in killing between the control and the test bacteria in PA phase. Azithromycin induced long PAEs in both S. pyogenes and H. influenzae and exhibited a slower bactericidal action on both the control and the bacteria in PA phase especially at the end of the PAE, when the killing was almost bacteriostatic. Our findings in this study support the concept that a long interval (> 12 h) between doses of azithromycin, restoring full bactericidal action, may be beneficial to optimize efficacy of this drug but is not necessary for the other antibiotics evaluated, since the bactericidal effect seems to be restored already at 4 h.

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Selected References

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  1. Brown M. R. Nutrient depletion and antibiotic susceptibility. J Antimicrob Chemother. 1977 May;3(3):198–201. doi: 10.1093/jac/3.3.198. [DOI] [PubMed] [Google Scholar]
  2. Bustamante C. I., Drusano G. L., Tatem B. A., Standiford H. C. Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984 Nov;26(5):678–682. doi: 10.1128/aac.26.5.678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. EAGLE H. Experimental approach to the problem of treatment failure with penicillin. I. Group A streptococcal infection in mice. Am J Med. 1952 Oct;13(4):389–399. doi: 10.1016/0002-9343(52)90293-3. [DOI] [PubMed] [Google Scholar]
  5. Eagle H., Musselman A. D. THE SLOW RECOVERY OF BACTERIA FROM THE TOXIC EFFECTS OF PENICILLIN. J Bacteriol. 1949 Oct;58(4):475–490. doi: 10.1128/jb.58.4.475-490.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gengo F. M., Mannion T. W., Nightingale C. H., Schentag J. J. Integration of pharmacokinetics and pharmacodynamics of methicillin in curative treatment of experimental endocarditis. J Antimicrob Chemother. 1984 Dec;14(6):619–631. doi: 10.1093/jac/14.6.619. [DOI] [PubMed] [Google Scholar]
  7. Gerber A. U., Craig W. A. Growth kinetics of respiratory pathogens after short exposures to ampicillin and erythromycin in vitro. J Antimicrob Chemother. 1981 Nov;8 (Suppl 100):81–91. doi: 10.1093/jac/8.suppl_c.81. [DOI] [PubMed] [Google Scholar]
  8. Gottfredsson M., Erlendsdóttir H., Gudmundsson A., Gudmundsson S. Different patterns of bacterial DNA synthesis during postantibiotic effect. Antimicrob Agents Chemother. 1995 Jun;39(6):1314–1319. doi: 10.1128/aac.39.6.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gudmundsson S., Vogelman B., Craig W. A. Decreased bactericidal activity during the period of the postantibiotic effect. J Antimicrob Chemother. 1994 Dec;34(6):921–930. doi: 10.1093/jac/34.6.921. [DOI] [PubMed] [Google Scholar]
  10. Gudmundsson S., Vogelman B., Craig W. A. The in-vivo postantibiotic effect of imipenem and other new antimicrobials. J Antimicrob Chemother. 1986 Dec;18 (Suppl E):67–73. doi: 10.1093/jac/18.supplement_e.67. [DOI] [PubMed] [Google Scholar]
  11. JAWETZ E., GUNNISON J. B., SPECK R. S., COLEMAN V. R. Studies on antibiotic synergism and antagonism; the interference of chloramphenicol with the action of penicillin. AMA Arch Intern Med. 1951 Mar;87(3):349–359. doi: 10.1001/archinte.1951.03810030022002. [DOI] [PubMed] [Google Scholar]
  12. Leggett J. E., Fantin B., Ebert S., Totsuka K., Vogelman B., Calame W., Mattie H., Craig W. A. Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. J Infect Dis. 1989 Feb;159(2):281–292. doi: 10.1093/infdis/159.2.281. [DOI] [PubMed] [Google Scholar]
  13. McDonald P. J., Craig W. A., Kunin C. M. Persistent effect of antibiotics on Staphylococcus aureus after exposure for limited periods of time. J Infect Dis. 1977 Feb;135(2):217–223. doi: 10.1093/infdis/135.2.217. [DOI] [PubMed] [Google Scholar]
  14. Odenholt I., Holm S. E., Cars O. Effects of benzylpenicillin on Streptococcus pyogenes during the postantibiotic phase in vitro. J Antimicrob Chemother. 1989 Aug;24(2):147–156. doi: 10.1093/jac/24.2.147. [DOI] [PubMed] [Google Scholar]
  15. Odenholt I., Holm S. E., Cars O. Effects of supra- and sub-MIC benzylpenicillin concentrations on group A beta-haemolytic streptococci during the postantibiotic phase in vivo. J Antimicrob Chemother. 1990 Aug;26(2):193–201. doi: 10.1093/jac/26.2.193. [DOI] [PubMed] [Google Scholar]
  16. Parker R. F., Marsh H. C. Action of Penicillin on Staphylococcus. J Bacteriol. 1946 Feb;51(2):181–186. [PMC free article] [PubMed] [Google Scholar]
  17. Tomasz A., Albino A., Zanati E. Multiple antibiotic resistance in a bacterium with suppressed autolytic system. Nature. 1970 Jul 11;227(5254):138–140. doi: 10.1038/227138a0. [DOI] [PubMed] [Google Scholar]
  18. Tuomanen E., Cozens R. Changes in peptidoglycan composition and penicillin-binding proteins in slowly growing Escherichia coli. J Bacteriol. 1987 Nov;169(11):5308–5310. doi: 10.1128/jb.169.11.5308-5310.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tuomanen E., Cozens R., Tosch W., Zak O., Tomasz A. The rate of killing of Escherichia coli by beta-lactam antibiotics is strictly proportional to the rate of bacterial growth. J Gen Microbiol. 1986 May;132(5):1297–1304. doi: 10.1099/00221287-132-5-1297. [DOI] [PubMed] [Google Scholar]
  20. Tuomanen E. Newly made enzymes determine ongoing cell wall synthesis and the antibacterial effects of cell wall synthesis inhibitors. J Bacteriol. 1986 Aug;167(2):535–543. doi: 10.1128/jb.167.2.535-543.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vogelman B., Gudmundsson S., Leggett J., Turnidge J., Ebert S., Craig W. A. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis. 1988 Oct;158(4):831–847. doi: 10.1093/infdis/158.4.831. [DOI] [PubMed] [Google Scholar]
  22. WOOD W. B., Jr, SMITH M. R. An experimental analysis of the curative action of penicillin in acute bacterial infections. I. The relationship of bacterial growth rates to the antimicrobial effect of penicillin. J Exp Med. 1956 Apr 1;103(4):487–498. doi: 10.1084/jem.103.4.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yan S., Bohach G. A., Stevens D. L. Persistent acylation of high-molecular-weight penicillin-binding proteins by penicillin induces the postantibiotic effect in Streptococcus pyogenes. J Infect Dis. 1994 Sep;170(3):609–614. doi: 10.1093/infdis/170.3.609. [DOI] [PubMed] [Google Scholar]

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