MACGOWAN AP, BOWKER KE; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. A-440.
BCARE, Bristol, United Kingdom
BACKGROUND: In vitro models offer an excellent way to study EoR as large numbers of bacteria (10[10] cfu) can be exposed to antibiotics. We simulated a range of moxifloxacin (mox) serum concentrations likely to occur with different human doses and followed EoR using Sp and Pa. METHODS: An in vitro dilutional model (central chamber volume 360ml; inoculum 10[8] cfu/mL) was used. 3 strains Sp (mox MIC 0.25, 1, 3.6mg/L) and 2 Pa (MIC 0.25, 1mg/L) were exposed to simulations of mox 200mg 24 hly, 400mg 24 h, 800mg 24 h, and 400mg 12 hly for 72 h. Experiments were performed in triplicate and EoR assessed by bacterial counts from the central chamber at 0, 12, 24, 36, 48, 60, 72h on to media with mox concentrations of 0x, 1x, 2x, 4x, 8x, 16x MIC. RESULTS: For Pa, 4.5 +/- 1.4 log cfu/mL were cultured on 4 x MIC plates at time 0, at 16 x MIC counts were <2 logs. No Sp were grown on MIC x 2 or other plates at time 0. No resistant colonies grew from any of the simulations with Sp. Resistance was noted with Pa which increased with time 72h >48h >24h >0h. EoR was related to drug exposure - [table: see text] Using an inhibitory Emax model, Cmax(Cm)/MIC and AUC[72] MIC could be related to log cfu/mL on 4 x MIC plates (R[2] 0.86, 0.82 respectively). Cm/MIC could be related to log cfu/mL on 16 x MIC plates (R[2] = 0.87) but AUC[72]/MIC could not. CONCLUSIONS: mox resistance is associated with (i) species (Pa > Sp) (ii) initial heterogenic population (Pa > Sp) (iii) time (long exposure > short) (iv) drug exposure small AUC[72]/MIC or Cm/MIC > large.
Publication Types:
Keywords:
- Area Under Curve
- Aza Compounds
- Bacteria
- Colony Count, Microbial
- Humans
- In Vitro
- Microbial Sensitivity Tests
- Quinolines
- moxifloxacin
- p-Aminosalicylic Acid
- pharmacokinetics
- pharmacology
Other ID:
UI: 102269101
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