Skip to main content
SpringerLink
Log in

Postantibiotic effect of ceftriaxone and gentamicin alone and in combination onKlebsiella pneumoniae, Pseudomonas aeruginosa andStreptococcus viridans

Der postantibiotische Effekt von Ceftriaxon and Gentamicin alleine und in Kombination gegenüberKlebsiella pneumoniae, Pseudomonas aeruginosa undStreptococcus viridans

  • Experimental Study
  • Published:
Infection Aims and scope Submit manuscript

Summary

A persistent suppression of bacterial growth following limited exposure to an antimicrobial agent, the postantibiotic effect (PAE), has been described for a variety of antibiotics and microorganisms. In this study the PAE of ceftriaxone and gentamicin was determinedin vitro on three strains each ofKlebsiella pneumoniae, Pseudomonas aeruginosa andStreptococcus viridans. The strains were exposed to the substances for 2 h at varying concentrations. Ceftriaxone was used at the minimal inhibitory concentration (MIC) and 1/2 MIC and gentamicin at 1/2 MIC, 1/4 MIC, and 1/8 MIC, each alone and in combination. Antibiotic concentrations were reduced by 1,000-fold dilution, bacterial regrowth was consequently monitored by viable count. The PAE of ceftriaxone alone reached up to 145 min (MIC) and 50 min (1/2 MIC), that of gentamicin alone up to 170 min (1/2 MIC), 135 min (1/4 MIC) and 70 min (1/8 MIC), depending on the bacterial species. Combinations of the antibiotics produced longer PAEs than one substance alone; the longest PAE was produced by the combination of ceftriaxone (MIC) and gentamicin (1/2 MIC) lasting up to 320 min (S. viridans). It may be important to take the PAE into account when evaluating dosing intervals.

Zusammenfassung

Eine dauerhafte Hemmung bakteriellen Wachstums nach Exposition gegenüber Antibiotika, genannt der postantibiotische Effekt (PAE), wurde bereits bei einer Reihe von antimikrobiellen Wirkstoffen und verschiedenen Mikroorganismen beobachtet. In dieser Studie wurde der PAE von Ceftriaxon und Gentamicin gegenüber jeweils drei Stämmen vonKlebsiella pneumoniae, Pseudomonas aeruginosa undStreptococcus viridans in vitro bestimmt. Die Isolate wurden hierzu für zwei Stunden mit verschiedenen Konzentrationen der Antibiotika inkubiert, bei Ceftriaxon waren dies die minimale Hemmkonzentration (MHK) und 1/2 MHK, bei Gentamicin 1/2 MHK, 1/4 MHK und 1/8 MHK, jeweils alleine und in Kombination. Die Wirkung der Antibiotika wurde danach durch 1000fache Verdünnung aufgehoben und das bakterielle Wachstum durch Keimzahlbestimmungen verfolgt. Der PAE von Ceftriaxon alleine reichte bis zu 145 min (MHK) und 50 min (1/2 MHK), von Gentamicin alleine bis zu 170 min (1/2 MHK), 135 min (1/4 MHK) und 70 min (1/8 MHK), abhängig von der Bakterienspezies. Kombinationen der beiden Antibiotika erzielten längere PAEs als eine Substanz alleine, der längste PAE konnte bei der Kombination von Ceftriaxon (MHK) und Gentamicin (1/2 MHK) mit einer Dauer bis zu 320 min (bei S. viridans) beobachtet werden. Das Vorhandensein und die Dauer eines PAEs könnten bei der Einschätzung und Bestimmung von Antibiotika-Dosierungsintervallen eine wichtige Rolle spielen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bigger, J. W. The bactericidal action of penicillin onStaphylococcus pyogenes. Ir. J. Med. Sc. 227 (1944) 533–568.

    Google Scholar 

  2. Parker, R. F., Luse, S. The action of penicillin onStraphylococcus: further observations on the effect of a short exposure. J. Bacteriol. 56 (1948) 75–81.

    Google Scholar 

  3. Eagle, H., Musselmann, A. D. The slow recovery of bacteria from the toxic effects of penicillin. J. Bacteriol. 58 (1949) 475–490.

    Google Scholar 

  4. Bodey, G. P., Pan, T. Effect of cephalothin on growth patterns of microorganisms. J. Antibiotics 29 (1976) 1092–1095.

    Google Scholar 

  5. McDonald, P. J., Craig, W. A., Kunin, C. M. Persistent effect of antibiotics onStaphylococcus aureus after exposure for limited periods of time. J. Infect. Dis. 135 (1977) 217–223.

    PubMed  Google Scholar 

  6. Rolinson, G. N. Plasma concentrations of penicillin in relation to the antibacterial effect. In:Davies, D. S., Prichard, B. N. C. (eds.): Biological effects of drugs in relation to their plasma concentrations. University Park Press, Baltimore 1973, pp. 183–189.

    Google Scholar 

  7. Krogstad, D. J., Moellering, R. C. Combinations of antibiotics, mechanisms of interaction against bacteria. In:Lorian, V. M. (ed.): Antibiotics in laboratory medicine. Williams & Wilkins, Baltimore 1980, pp. 298–341.

    Google Scholar 

  8. Hook, E. W., Roberts, R. B., Sande, M. A. Antimicrobial therapy of experimental enterococcal endocarditis. Antimicrob. Agents Chemother. 8 (1975) 564–570.

    PubMed  Google Scholar 

  9. Johnson, D. E., Thompson, B., Calia, F. M. Comparative activities of piperacillin, ceftazidime, and amikacin, alone and in all possible combinations, against experimentalPseudomondas aeruginosa infections in neutropenic rats. Antimicrob. Agents Chemother. 28 (1985) 735–739.

    PubMed  Google Scholar 

  10. Klastersky, J., Meunier-Carpentier, F., Prevost, J.-M. Significance of antimicrobial synergism for the outcome of gram-negative sepsis. Am. J. Med. Sc. 273 (1977) 157–167.

    Google Scholar 

  11. Fuursted, K. Comparison of the post-antibiotic effect ofStreptococcus faecalis andStreptococcus faecium with ampicillin alone or combined with streptomycin: studies on a novel type of antimicrobial interaction. Acta Path. Microbiol. Immunol. Scand. Section B 95 (1987) 351–354.

    Google Scholar 

  12. Fuursted, K. Comparative killing activity and post-antibiotic effect of streptomycin combined with ampicillin, ciprofloxacin, imipenem, piperacillin or vancomycin against strains ofStreptococcus faecalis andStreptococcus faecium. Chemotherapy 34 (1988) 229–234.

    PubMed  Google Scholar 

  13. Hessen, M. T., Pitsakis, P. G., Levison, M. E.: Potentiation of post-antibiotic effect with antibiotic combinations. 26th ICAAC., USA 1986, abstr. 584.

  14. Hessen, M. T., Pitsakis, P. G., Levison, M. E.: Postantibiotic effect of penicillin plus gentamicin versusEnterococcus fecalis in vitro andin vivo. Antimicrob. Agents Chemother. (1989) 608–611.

  15. Isaksson, B., Hanberger, H., Maller, R., Nilsson, L. E., Nilsson, M. Synergistic postantibiotic effect of amikacin andβ-lactam antibiotics onEnterococcus faecalis. J. Antimicrob. Chemother. 27 (Suppl. C9) (1991) 9–14.

    Google Scholar 

  16. Wistanley, T. G., Hastings, J. G. M. Penicillin-aminoglycoside synergy and postantibiotic effect for enterococci. J. Antimicrob. Chemother. 23 (1989) 189–199.

    PubMed  Google Scholar 

  17. National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: Tentative Standard M7-T4. NCCLS (1988), Villanova, PA.

  18. Bundtzen, R. W., Gerber, A. U., Cohn, D. L., Craig, W. A. Postantibiotic suppression of bacterial growth. Rev. Infect. Dis. 3 (1981) 28–37.

    PubMed  Google Scholar 

  19. Eagle, H. The recovery of bacteria from the toxic effects of penicillin. J. Clin. Invest. 28 (1949) 832–836.

    Google Scholar 

  20. Baquero, F., Culebras, E., Patron, C., Perez-Diaz, J. C., Medrano, J. C., Vicente, M. F. Postantibiotic effect on gram-positive and gram-negative micro-organisms. J. Antimicrob. Chemother. 18 (Suppl. E) (1986) 47–49.

    Google Scholar 

  21. Bustamante, C. L., Drusano, G. L., Tatem, B. A., Standiford, H. C. Postantibiotic effect of imipenem onPseudomonas aeruginosa. Antimicrob. Agents Chemother. 26 (1984) 678–682.

    PubMed  Google Scholar 

  22. Eagle, H., Fleischmann, R., Musselman, A. D. The bacterial action of penicillinin vivo, the participation of the host and the slow recovery of the surviving organisms. Ann. Intern. Med. 33 (1950) 544–571.

    PubMed  Google Scholar 

  23. Craig, W. A. Concluding remarks from the pharmacokinetic and experimental data on beta-lactam antibiotics in the treatment of patients. Eur. J. Clin. Microbiol. 3 (1984) 575–578.

    PubMed  Google Scholar 

  24. Bailey and Scott: Diagnostic Microbiology, 9th ed., Mosby, St. Louis, 1994.

  25. Kuenzi, B., Segessenmann, Ch., Gerber, A. U. Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected gram-positive bacteria andHaemophilus influenzae. J. Antimicrob. Chemother. 20 (Suppl. B) (1987) 39–46.

    PubMed  Google Scholar 

  26. Isaksson, B., Nilsson, L., Maller, R., Sören, L. Postantibiotic effect of aminoglycosides on gram-negative bacteria evaluated by a new method. J. Antimicrob. Chemother. 22 (1988) 23–33.

    Google Scholar 

  27. Isaksson, B., Hanberger, H., Maller, R., Nilsson, L. E., Nilsson, M. Synergic postantibiotic effect of amikacin in combination withβ-lactam antibiotics on gram-negative bacteria. J. Antimicrob. Chemother. 28 (1991) 25–34.

    Google Scholar 

  28. Craig, W. A., Gudmundssonn, S. The postantibiotic effect. 3rd ed. In:Lorian, V. (ed.): Antibiotics in laboratory medicine, Williams & Wilkins, Baltimore 1991, 403–431.

    Google Scholar 

  29. White, G. M., Malow, J. B., Zimelis, V. M., Pahlavanzadeh, H., Panwalker, A. P., Jackson, G. Comperativein vitro activity of azlocillin, ampicillin, mezlocillin, piperacillin, and ticarcillin, alone and in combination with an aminoglycoside. Antimicrob. Agents Chemother. 15 (1979) 540–543.

    PubMed  Google Scholar 

  30. Paglia, P., Molinari, G., Pesce, A., Debbia, E. A. Dactimicin, a new aminoglycoside:in vitro activity, postantibiotic effect and interaction with other antibiotics. Eur. J. Clin. Microbiol. Infect. Dis. 8 (1989) 639–643.

    PubMed  Google Scholar 

  31. McLaughlin, J. E., Reeves, D. S. Clinical and laboratory evidence for inactivation of gentamicin by carbenicillin. Lancet i (1971) 261–264.

    Google Scholar 

  32. Weibert, R., Keane, W., Shapiro, F. Carbenicillin inactivation of aminoglycosides in patients with severe renal failure. Transactions of the Am. Soc. Artific. Int. Org. 22 (1976) 439–443.

    Google Scholar 

  33. Pechere, J. C., Craig, W. A., Meunier, F. Once daily dosing of aminoglycoside: one step forward. J. Antimicrob. Chemother. 27 (Suppl. C) (1991) 149–152.

    PubMed  Google Scholar 

  34. McDonald, P. J., Wetherall, B. L., Pruul, H. Postantibiotic leukocyte enhancement: increased susceptibility of bacteria pretreated with antibiotics to activity of leukocytes. Rev. Infect. Dis. 3 (1981) 38–44.

    PubMed  Google Scholar 

  35. Gerber, A. U., Craig, W. A. Growth kinetics of respiratory pathogens after short exposures to ampicillin and erythromycinin vitro. J. Antimicrob. Chemother. 8 (Suppl. C) (1981) 81–91.

    Google Scholar 

  36. Craig, W. A. Post antibiotic effects in experimental infection models: relationship toin-vitro phenomena and to treatment of infections in man. J. Antimicrob. Chemother. 31 (Suppl. D) (1993) 149–158.

    PubMed  Google Scholar 

  37. Gilbert, D. N. Once-daily aminoglycoside therapy. Antimicrob. Agents Chemother. 35 (1991) 399–405.

    PubMed  Google Scholar 

  38. Pechere, J. C., Bernard, P. A.: Gentamicin ototoxicity can be avoided if a new therapeutic regimen is used. An experimental animal model. 24th ICAAC, USA 1984, abstr. 484.

  39. ter Braak, E. W., de Vries, P. J., Bouter, K. P., van der Vegt, S. G., Dorrestein, G. C., Nortier, J. W. Once daily dosing regimen for aminoglycoside plusβ-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone. Am. J. Med. 89 (1990) 58–66.

    PubMed  Google Scholar 

  40. Tulkens, P. M. Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data. Scand. J. Infect. Dis. 74 (1991) 249–257.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinische Abteilung für Infektionen und Chemotherapie, Allgemeines Krankenhaus der Stadt Wien, Universitätsklinik für Innere Medizin I, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    Astrid Buxbaum &  A. Georgopoulos

Authors
  1. Astrid Buxbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Georgopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buxbaum, A., Georgopoulos, A. Postantibiotic effect of ceftriaxone and gentamicin alone and in combination onKlebsiella pneumoniae, Pseudomonas aeruginosa andStreptococcus viridans . Infection 24, 459–464 (1996). https://doi.org/10.1007/BF01713048

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01713048

Keywords

Search

Navigation