High doses of levofloxacin vs moxifloxacin against staphylococcal experimental foreign-body infection: the effect of higher MIC-related pharmacokinetic parameters on efficacy.
OBJECTIVE
Since levofloxacin at high doses was the best therapy in staphylococcal tissue-cage model of foreign-body infection, we hypothesized that moxifloxacin with higher ratio of area under the concentration-time curve to the MIC (AUC/MIC) would provide better results.


METHODS
MICs, MBCs, MPCs (mutant prevention concentration) and 24h kill-curves were determined in the log and stationary phases. Using the aforementioned model, we tested the efficacy of levofloxacin 100mg/kg/d, moxifloxacin 40mg/kg/d and moxifloxacin 80mg/kg/d; they were equivalent to human levels for 1000mg/d, 400mg/d and 800mg/d, respectively. We screened for the appearance of resistant strains.


RESULTS
MICs and MBCs in logarithmic and stationary phases and MPCs of levofloxacin were 0.5, 1 and 4, 0.8microg/ml, respectively, and those of moxifloxacin 0.12, 0.25 and 2, 0.25microg/ml. AUC/MIC were 234 (levofloxacin), 431 (moxifloxacin 40) and 568 (moxifloxacin 80). Bacterial counts decreases in tissue-cage fluids (means of logCFU/ml) were -1.81 (n=25), -1.31 (23), and -1.46 (20), respectively; for controls it was 0.24 (22). All groups were better than controls (p<0.05); no differences between them existed.


CONCLUSIONS
Moxifloxacin with higher AUC/MIC ratio did not improve the efficacy of high doses of levofloxacin.
Murillo
Oscar
O
Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, L'Hospitalet de Llobregat, Barcelona, Spain. 32186omr@comb.es
Pachón
M Eugenia
ME
Euba
Gorane
G
Verdaguer
Ricard
R
Tubau
Fe
F
Cabellos
Carmen
C
Cabo
Javier
J
Gudiol
Francesc
F
Ariza
Javier
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D024841:Fluoroquinolones; D005547:Foreign Bodies / Q000150:complications*; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D023421:Models, Animal; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin