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.
References
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
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
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
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
Thore A, Åhséhn S, Lundin A, Bergman S (1975) Detection of bacteria by luciferase assay of adenosine triphosphate. J Clin Microbiol 1:1–8
O´Hare MD, Reynolds PE (1992) Novel membrane proteins in teicoplanin-resistant, vancomycin-sensitive, coagulase-negative Staphylococcus spp. J Antimicrob Chemother 30:753–768
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
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
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
Livornese LL Jr, Korzeniowski OM (1992) Pathogenesis of infective endocarditis. In: Kaye D (ed) Infective endocarditis, 2nd edn. Raven, New York pp 19–35
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
Small PM, Chambers HF (1990) Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 34:1227–1231
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
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
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
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This study was supported in part by the County Council of Östergötland, Sweden. All the experiments done comply with current Swedish laws.
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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
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DOI: https://doi.org/10.1007/s10096-005-0011-0