title: Impact of poor compliance with levofloxacin and moxifloxacin on respiratory tract infection antimicrobial efficacy: a pharmacokinetic/pharmacodynamic simulation study.
abstract: 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 500 mg every 24h (q24 h) or every 12h (q12h), LFX 750 mg q24 h and MOX 400mg q24 h 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 500 mg q24 h was not able to reach the PK/PD index guaranteeing clinical efficacy. With LFX 500 mg q12 h or 750 mg q24 h, 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 q24 h, the probability of achieving this PK/PD index is maintained with delay in dosing up to 16h. In conclusion, LFX 500 mg q24 h is the least robust treatment against S. pneumoniae, H. influenzae and M. catarrhalis in a non-adherence situation. A good choice is LFX 500 mg q12h, but in order to favour patient adherence, LFX 750 mg q24 h or MOX 400mg q24h appears as more appropriate.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Basque Country, 48940 Leioa, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Carral
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Basque Country, 48940 Leioa, Spain; Dynakin, S.L., PTB 801, 14890 Derio, Vizcaya, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Lukas
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Basque Country, 48940 Leioa, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Oteo
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Basque Country, 48940 Leioa, Spain. Electronic address: elena.suarez@ehu.es.
authors.forename: E
authors.initials: E
authors.lastname: Suarez
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D015233:Models, Statistical; D001936:Moraxella catarrhalis / Q000187:drug effects; D000077266:Moxifloxacin; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D064704:Levofloxacin; D000077266:Moxifloxacin
keywords: Levofloxacin; Monte Carlo simulation; Moxifloxacin; Non-adherence; Pharmacokinetics/pharmacodynamics