Skip to main content
Log in

Abstract

Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min. No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. König C, Simmen HP, Blaser J (1998) Bacterial concentrations in pus and infected peritoneal fluid—implications for bactericidal activity of antibiotics. J Antimicrob Chemother 42:227–232

    Article  PubMed  Google Scholar 

  2. Sanyal D, Johnson AP, George RC, Edwards R, Greenwood D (1993) In-vitro characteristics of glycopeptide-resistant strains of Staphylococcus epidermidis isolated from patients on CAPD. J Antimicrob Chemother 32:267–278

    Article  PubMed  CAS  Google Scholar 

  3. Sieradzki K, Villari P, Tomasz A (1998) Decreased susceptibilities to teicoplanin and vancomycin among coagulase-negative methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother 42:100–107

    PubMed  CAS  Google Scholar 

  4. Sieradzki K, Roberts RB, Haber SW, Tomasz A (1999) The development of vancomycin resistance in a patient with methicillin-resistant Staphylococcus aureus infection. N Engl J Med 340:517–523

    Article  PubMed  CAS  Google Scholar 

  5. Thore A, Åhséhn S, Lundin A, Bergman S (1975) Detection of bacteria by luciferase assay of adenosine triphosphate. J Clin Microbiol 1:1–8

    PubMed  CAS  Google Scholar 

  6. O´Hare MD, Reynolds PE (1992) Novel membrane proteins in teicoplanin-resistant, vancomycin-sensitive, coagulase-negative Staphylococcus spp. J Antimicrob Chemother 30:753–768

    Article  PubMed  CAS  Google Scholar 

  7. Sieradzki K, Tomasz A (1997) Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus. J Bacteriol 179:2557–2566

    PubMed  CAS  Google Scholar 

  8. Cui L, Ma X, Katsuhiro S, Okuma K, Tenover FC, Mamizuka EM, Gemmell CG, Kim M, Ploy M, El Sohl N, Ferraz V, Hiramatsu K (2003) Cell wall thickening is a common feature of vancomycin resistance in Staphylococcus aureus. J Clin Microbiol 41:5–14

    Article  PubMed  CAS  Google Scholar 

  9. Greenwood D, Bidgood K, Turner M (1987) A comparison of the responses of staphylococci and streptococci to teicoplanin and vancomycin. J Antimicrob Chemother 20:155–164

    Article  PubMed  CAS  Google Scholar 

  10. Livornese LL Jr, Korzeniowski OM (1992) Pathogenesis of infective endocarditis. In: Kaye D (ed) Infective endocarditis, 2nd edn. Raven, New York pp 19–35

    Google Scholar 

  11. La Plante KL, Rybak MJ (2004) Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model. Antimicrob Agents Chemother 48:4665–4672

    Article  PubMed  CAS  Google Scholar 

  12. Small PM, Chambers HF (1990) Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 34:1227–1231

    PubMed  CAS  Google Scholar 

  13. Levine DP, Fromm BS, Reddy BR (1991) Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 115:674–680

    PubMed  CAS  Google Scholar 

  14. Fortún J, Navas E, Martínez-Beltrán J, Pérez-Molina J, Martín-Dávila P, Guerrero A, Moreno S (2001) Short-course therapy for right-sided endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clin Infect Dis 33:120–125

    Article  PubMed  Google Scholar 

  15. Nicolau DP, Freeman CD, Nightingale CH, Coe CJ, Quintiliani R (1994) Minocycline versus vancomycin for treatment of experimental endocarditis caused by oxacillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 38:1515–1518

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by the County Council of Östergötland, Sweden. All the experiments done comply with current Swedish laws.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Ekdahl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ekdahl, C., Hanberger, H., Hällgren, A. et al. Rapid decrease of free vancomycin in dense staphylococcal cultures. Eur J Clin Microbiol Infect Dis 24, 596–602 (2005). https://doi.org/10.1007/s10096-005-0011-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-005-0011-0

Keywords

Navigation