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. 1997 Apr;41(4):781–784. doi: 10.1128/aac.41.4.781

Comparative study of bactericidal activities, postantibiotic effects, and effects of bacterial virulence of penicillin G and six macrolides against Streptococcus pneumoniae.

K Fuursted 1, J D Knudsen 1, M B Petersen 1, R L Poulsen 1, D Rehm 1
PMCID: PMC163794  PMID: 9087489

Abstract

In this report, we present MIC, bactericidal activity, postantibiotic effect (PAE), and in vivo infectivity data for postantibiotic-phase pneumococci. We compared and evaluated penicillin G and six macrolides, erythromycin, azithromycin, clarithromycin, dirithromycin, roxithromycin, and spiramycin, against 10 strains of pneumococci with various levels of susceptibility to penicillin. All of the agents, except azithromycin, exhibited a bactericidal effect (a > or = 3 log10 decrease in the number of CFU per milliliter) after 4 h of exposure to a concentration equal to 10 times the MIC, displaying the following hierarchy: spiramycin = penicillin G = erythromycin = dirithromycin = clarithromycin = roxithromycin > azithromycin. The bactericidal rate of penicillin G was significantly lower for resistant strains (MIC, > or = 2 microg/ml), while bactericidal rates of macrolides were unaffected by penicillin susceptibility. A PAE was induced in all of the strains by all of the antibiotics after exposure for 1 h to a concentration equivalent to 10 times the MIC. The mean duration of PAEs varied between 2.3 and 3.9 h, showing the following hierarchy: spiramycin = dirithromycin = clarithromycin = erythromycin = roxithromycin > azithromycin > penicillin G. Virulence studies were performed with immunocompetent mice by intraperitoneal inoculation of virulent, penicillin-susceptible serotype 3 pneumococci which had been pre-exposed to penicillin G or a macrolide for 1 h. A significant decrease in the virulence of postantibiotic-phase pneumococci was induced only by erythromycin, azithromycin, dirithromycin, and spiramycin, displaying 5.9-, 7.1-, 4.2-, and 3.6-fold increases in the 50% lethal dose (LD50) compared to a control suspension, respectively. No significant correlation could be demonstrated between the LD50 and the MIC, bactericidal activity, or PAE duration. These results suggest that antimicrobial interaction with host defenses in terms of virulence might be a significant parameter that could influence the drug or drug regimen of choice.

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Selected References

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  1. Appelbaum P. C. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992 Jul;15(1):77–83. doi: 10.1093/clinids/15.1.77. [DOI] [PubMed] [Google Scholar]
  2. Bauernfeind A. In-vitro activity of dirithromycin in comparison with other new and established macrolides. J Antimicrob Chemother. 1993 Mar;31 (Suppl 100):39–49. doi: 10.1093/jac/31.suppl_c.39. [DOI] [PubMed] [Google Scholar]
  3. Brogden R. N., Peters D. H. Dirithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994 Oct;48(4):599–616. doi: 10.2165/00003495-199448040-00008. [DOI] [PubMed] [Google Scholar]
  4. Bundtzen R. W., Gerber A. U., Cohn D. L., Craig W. A. Postantibiotic suppression of bacterial growth. Rev Infect Dis. 1981 Jan-Feb;3(1):28–37. doi: 10.1093/clinids/3.1.28. [DOI] [PubMed] [Google Scholar]
  5. Chabbert Y. A. Early studies on in-vitro and experimental activity of spiramycin: a review. J Antimicrob Chemother. 1988 Jul;22 (Suppl B):1–11. doi: 10.1093/jac/22.supplement_b.1. [DOI] [PubMed] [Google Scholar]
  6. EAGLE H., FLEISCHMAN R., MUSSELMAN A. D. The bactericidal action of penicillin in vivo: the participation of the host, and the slow recovery of the surviving organisms. Ann Intern Med. 1950 Sep;33(3):544–571. doi: 10.7326/0003-4819-33-3-544. [DOI] [PubMed] [Google Scholar]
  7. Holloway P. M., Bucknall R. A., Denton G. W. The effects of sub-lethal concentrations of chlorhexidine on bacterial pathogenicity. J Hosp Infect. 1986 Jul;8(1):39–46. doi: 10.1016/0195-6701(86)90103-9. [DOI] [PubMed] [Google Scholar]
  8. Kuenzi B., Segessenmann C., Gerber A. U. Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected gram-positive bacteria and Haemophilus influenzae. J Antimicrob Chemother. 1987 Nov;20 (Suppl B):39–46. doi: 10.1093/jac/20.suppl_b.39. [DOI] [PubMed] [Google Scholar]
  9. Majcherczyk P. A. The issue of the true postantibiotic effect. J Antimicrob Chemother. 1996 Jan;37(1):188–190. doi: 10.1093/jac/37.1.188. [DOI] [PubMed] [Google Scholar]
  10. Odenholt-Tornqvist I., Löwdin E., Cars O. Pharmacodynamic effects of subinhibitory concentrations of beta-lactam antibiotics in vitro. Antimicrob Agents Chemother. 1991 Sep;35(9):1834–1839. doi: 10.1128/aac.35.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Odenholt-Tornqvist I., Löwdin E., Cars O. Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens. Antimicrob Agents Chemother. 1995 Jan;39(1):221–226. doi: 10.1128/aac.39.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Poulsen R. L., Knudsen J. D., Petersen M. B., Fuursted K., Espersen F., Frimodt-Møller N. In vitro activity of six macrolides, clindamycin and tetracycline on Streptococcus pneumoniae with different penicillin susceptibilities. APMIS. 1996 Mar;104(3):227–233. [PubMed] [Google Scholar]
  13. Pruul H., McDonald P. J. Damage to bacteria by antibiotics in vitro and its relevance to antimicrobial chemotherapy: a historical perspective. J Antimicrob Chemother. 1988 Jun;21(6):695–698. doi: 10.1093/jac/21.6.695. [DOI] [PubMed] [Google Scholar]
  14. Ramadan M. A., Tawfik A. F., Shibl A. M., Gemmell C. G. Post-antibiotic effect of azithromycin and erythromycin on streptococcal susceptibility to phagocytosis. J Med Microbiol. 1995 May;42(5):362–366. doi: 10.1099/00222615-42-5-362. [DOI] [PubMed] [Google Scholar]
  15. Rotter M. L., Hirschl A. M., Koller W. Effect of chlorhexidine-containing detergent, non-medicated soap or isopropanol and the influence of neutralizer on bacterial pathogenicity. J Hosp Infect. 1988 Apr;11(3):220–225. doi: 10.1016/0195-6701(88)90100-4. [DOI] [PubMed] [Google Scholar]
  16. Shibl A. M., Pechère J. C., Ramadan M. A. Postantibiotic effect and host-bacteria interactions. J Antimicrob Chemother. 1995 Dec;36(6):885–887. doi: 10.1093/jac/36.6.885. [DOI] [PubMed] [Google Scholar]
  17. Watson D. A., Musher D. M., Verhoef J. Pneumococcal virulence factors and host immune responses to them. Eur J Clin Microbiol Infect Dis. 1995 Jun;14(6):479–490. doi: 10.1007/BF02113425. [DOI] [PubMed] [Google Scholar]
  18. Winstanley T. G. Penicillin-induced post antibiotic effects on streptococci in vitro and in vivo. J Antimicrob Chemother. 1990 Aug;26(2):165–168. doi: 10.1093/jac/26.2.165. [DOI] [PubMed] [Google Scholar]

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