PMID- 15980331
OWN - NLM
STAT- MEDLINE
DCOM- 20050819
LR  - 20181113
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 49
IP  - 7
DP  - 2005 Jul
TI  - Antistaphylococcal effect related to the area under the curve/MIC ratio in an in 
      vitro dynamic model: predicted breakpoints versus clinically achievable values 
      for seven fluoroquinolones.
PG  - 2642-7
AB  - Prediction of the relative efficacies of different fluoroquinolones is often 
      based on the ratios of the clinically achievable area under the 
      concentration-time curve (AUC) to the MIC, usually with incorporation of the 
      MIC50 or the MIC90 and with the assumption of antibiotic-independent patterns of 
      the AUC/MIC-response relationships. To ascertain whether this assumption is 
      correct, the pharmacodynamics of seven pharmacokinetically different quinolones 
      against two clinical isolates of Staphylococcus aureus were studied by using an 
      in vitro model. Two differentially susceptible clinical isolates of S. aureus 
      were exposed to two 12-h doses of ciprofloxacin (CIP) and one dose of 
      gatifloxacin (GAT), gemifloxacin (GEM), grepafloxacin (GRX), levofloxacin (LVX), 
      moxifloxacin (MXF), and trovafloxacin (TVA) over similar AUC/MIC ranges from 58 
      to 932 h. A specific bacterial strain-independent AUC/MIC relationship with the 
      antimicrobial effect (I(E)) was associated with each quinolone. Based on the 
      I(E)-log AUC/MIC relationships, breakpoints (BPs) that are equivalent to a CIP 
      AUC/MIC ratio of 125 h were predicted for GRX, MXF, and TVA (75 to 78 h), GAT and 
      GEM (95 to 103 h) and LVX (115 h). With GRX and LVX, the predicted BPs were close 
      to those established in clinical settings (no clinical data on other quinolones 
      are available in the literature). To determine if the predicted AUC/MIC BPs are 
      achievable at clinical doses, i.e., at the therapeutic AUCs (AUC(ther)s), the 
      AUC(ther)/MIC50 ratios were studied. These ratios exceeded the BPs for GAT, GEM, 
      GRX, MXF, TVA, and LVX (750 mg) but not for CIP and LVX (500 mg). AUC/MIC ratios 
      above the BPs can be considered of therapeutic potential for the quinolones. The 
      highest ratios of AUC(ther)/MIC50 to BP were achieved with TVA, MXF, and GEM (2.5 
      to 3.0); intermediate ratios (1.5 to 1.6) were achieved with GAT and GRX; and 
      minimal ratios (0.3 to 1.2) were achieved with CIP and LVX.
FAU - Firsov, Alexander A
AU  - Firsov AA
AD  - Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New 
      Antibiotics, Russian Academy of Medical Sciences, 11 Bolshaya Pirogovskaya St., 
      Moscow 119021, Russia. firsov@dol.ru
FAU - Lubenko, Irene Y
AU  - Lubenko IY
FAU - Vostrov, Sergey N
AU  - Vostrov SN
FAU - Portnoy, Yury A
AU  - Portnoy YA
FAU - Zinner, Stephen H
AU  - Zinner SH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Fluoroquinolones)
SB  - IM
MH  - Anti-Infective Agents/*pharmacokinetics/*pharmacology
MH  - Area Under Curve
MH  - Dose-Response Relationship, Drug
MH  - Fluoroquinolones/*pharmacokinetics/*pharmacology
MH  - Half-Life
MH  - Humans
MH  - Microbial Sensitivity Tests/standards
MH  - Models, Biological
MH  - Staphylococcus aureus/*drug effects/growth & development
PMC - PMC1168651
EDAT- 2005/06/28 09:00
MHDA- 2005/08/20 09:00
PMCR- 2005/07/01
CRDT- 2005/06/28 09:00
PHST- 2005/06/28 09:00 [pubmed]
PHST- 2005/08/20 09:00 [medline]
PHST- 2005/06/28 09:00 [entrez]
PHST- 2005/07/01 00:00 [pmc-release]
AID - 49/7/2642 [pii]
AID - 0374-04 [pii]
AID - 10.1128/AAC.49.7.2642-2647.2005 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2005 Jul;49(7):2642-7. doi: 
      10.1128/AAC.49.7.2642-2647.2005.