Impact of poor compliance with levofloxacin and moxifloxacin on respiratory tract infection antimicrobial efficacy: A pharmacokinetic/pharmacodynamic simulation study
2015
Carral, N. | Lukas, J.C. | Oteo, I. | Suarez, E.
The purpose of this report was to assess the impact of poor compliance on the efficacy of levofloxacin (LFX) and moxifloxacin (MOX), two fluoroquinolones with different pharmacokinetic (PK) and pharmacodynamic (PD) properties, in respiratory infections. The fAUC0–24h and fAUC0–24h/MIC90 ratio, a PK/PD index predictive of bacterial eradication, were extracted from previously described population PK models for LFX and MOX. The MIC90 was according to EUCAST. Monte Carlo simulations were used with LFX 500mg every 24h (q24h) or every 12h (q12h), LFX 750mg q24h and MOX 400mg q24h in non-compliance scenarios to derive the proportion of patients achieving target ratios of fAUC0–24h/MIC90>33.8 for Streptococcus pneumoniae and >100 for Haemophilus influenzae and Moraxella catarrhalis (PTA>90%). In non-adherent dosing scenarios, LFX 500mg q24h was not able to reach the PK/PD index guaranteeing clinical efficacy. With LFX 500mg q12h or 750mg q24h, this probability was maintained although patients can take the dose with delays of up to 12h and 11h, respectively, for the three bacterial types. With MOX 400mg q24h, the probability of achieving this PK/PD index is maintained with delay in dosing up to 16h. In conclusion, LFX 500mg q24h is the least robust treatment against S. pneumoniae, H. influenzae and M. catarrhalis in a non-adherence situation. A good choice is LFX 500mg q12h, but in order to favour patient adherence, LFX 750mg q24h or MOX 400mg q24h appears as more appropriate.
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