Previous Article | Next Article ![]()
Antimicrobial Agents and Chemotherapy, November 1998, p. 2848-2852, Vol. 42, No. 11
Department of Pharmacokinetics, Centre of
Science & Technology LekBioTech, Moscow,
Russia1;
Division of Infectious
Diseases, Department of Medicine, Brown University, Providence,
Rhode Island2; and
Institute of
Microbiology, University of Verona, Verona, Italy3
Received 30 January 1998/Returned for modification 7 March
1998/Accepted 12 August 1998
Multiple predictors of fluoroquinolone antimicrobial effects (AMEs)
are not usually examined simultaneously in most studies. To compare
the predictive potentials of the area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC), the AUC above MIC
(AUCeff), and the time above MIC
(Teff), the kinetics of killing and regrowth of
four bacterial strains exposed to monoexponentially decreasing concentrations of ciprofloxacin were studied in an in vitro
dynamic model. The MICs of ciprofloxacin for clinical isolates of
Staphylococcus aureus, Escherichia coli
11775 (I) and 204 (II), and Pseudomonas aeruginosa were
0.6, 0.013, 0.08, and 0.15 µg/ml, respectively. The simulated values
of AUC were designed to provide similar 1,000-fold (S. aureus, E. coli I, and P. aeruginosa) or 2,000-fold (E. coli II) ranges of
the AUC/MIC. In each case except for the highest AUC/MIC ratio, the
observation periods included complete regrowth in the time-kill curve
studies. The AME was expressed by its intensity, IE (the area between the control growth and
time-kill and regrowth curves up to the point where the viable counts
of regrowing bacteria are close to the maximum values observed without
drug). For most AUC ranges the IE-AUC curves
were fitted by an Emax (maximal effect) model,
whereas the effects observed at very high AUCs were greater than those
predicted by the model. The AUCs that produced 50% of maximal AME were
proportional to the MICs for the strains studied, but maximal AMEs
(IEmax) and the extent of sigmoidicity (s) were not related to the MIC. Both
Teff and log AUC/MIC correlated well with
IE (r2 = 0.98 in both cases) in a species-independent fashion. Unlike Teff or log AUC/MIC, a specific relationship
between IE and log AUCeff was
inherent in each strain. Although each IE and
log AUCeff plot was fitted by linear regression
(r2 = 0.97 to 0.99), these plots were
not superimposed and therefore are bacterial species dependent. Thus,
AUC/MIC and Teff were better predictors of
ciprofloxacin's AME than AUCeff. This study suggests that
optimal predictors of the AME produced by a given quinolone (intraquinolone predictors) may be established by examining its AMEs
against bacteria of different susceptibilities.
Teff was shown previously also to be the best
interquinolone predictor, but unlike AUC/MIC, it cannot be used to
compare different quinolones. AUC/MIC might be the best predictor of
the AME in comparisons of different quinolones.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
MIC-Based Interspecies Prediction of the Antimicrobial Effects of
Ciprofloxacin on Bacteria of Different Susceptibilities in an In
Vitro Dynamic Model
*
Corresponding author. Mailing address: Department of
Pharmacokinetics, Centre of Science & Technology LekBioTech,
8 Nauchny proezd, Moscow, 117246 Russia. Phone: 7(095)332-34-35. Fax:
7(095)331-01-01. E-mail: Biotec{at}glas.apc.org.
This article has been cited by other articles:
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»