Pharmacokinetics and penetration of moxifloxacin into infected diabetic foot tissue in a large diabetic patient cohort

Objectives: Physiological changes occurring in patients with diabetes may affect the pharmacokinetics and penetration of antimicrobial agents into peripheral tissue. We examined the pharmacokinetics and the penetration of moxifloxacin into perinecrotic tissue of diabetic foot lesions in patients with diabetic foot infections (DFI). Patients and methods: Adult patients suffering from type 2 diabetes mellitus and hospitalized for DFI (Texas classification of at least B2) were treated with 400 mg moxifloxacin intravenously (IV) or orally (PO) once daily. The pharmacokinetics of moxifloxacin and its concentration 3 h after administration in samples of perinecrotic tissue resected from infected diabetic foot wounds were determined at steady state (days 4-8). Results: A total of 53 patients with diabetes mellitus type 2 (mean age 69.4±10.8 years) were included in the study, of whom 28 received PO and 25 IV moxifloxacin therapy for a median of 8 days. In the PO and IV subgroups, the mean maximum observed plasma concentration (C _max) in plasma was 2.69 and 4.77 mg/l at a median of 2 [time to reach C _max (T _max) range 1.0-8.0 h] and 1 h after administration, respectively. A mean area under the plasma concentration-time curve from time 0 until the last quantifiable plasma concentration (AUC_{0-24 h}) of 29.36 mg h/l (PO) and 27.09 mg h/l (IV) was achieved. Mean moxifloxacin concentrations in perinecrotic tissue of infected diabetic foot wounds following PO or IV administration were 1.79±0.82 and 2.20±1.54 μg/g, thus exceeding the MIC ₉₀ (minimum inhibitory concentration required to inhibit growth of 90% of organisms) for Staphylococcus aureus (0.25 mg/l) by seven-and eightfold and the MIC₉₀ for Escherichia coli (0.06 mg/l) by 29-fold and 36-fold, respectively. The mean tissue-to-plasma ratios of moxifloxacin concentration 3 h after administration were 1.01±0.57 (PO) and 1.09±0.69 (IV). Significant differences between the routes of administration were observed for T _max and C _max (P<0.01), but not for other clinically relevant parameters (AUC _0-24; moxifloxacin DFI tissue concentration). Conclusions: The plasma concentration-time curve of moxifloxacin in diabetic patients is similar to that of healthy volunteers. We also observed a good penetration of moxifloxacin into inflamed DFI tissue which taken together with the possibility of sequential IV/PO therapy suggest that moxifloxacin 400 mg once daily is a therapeutic option in the treatment of DFI caused by susceptible organisms.