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Objective: To assess the pharmacokinetic and pharmacodynamic behaviour of Abstract moxifloxacin in 15 consecutive elderly patients with acute exacerbation of chronic bronchitis (AECB) treated with the fixed oral moxifloxacin 400 mg/day regimen with the intent of verifying which degree of exposure may be ensured by this standard regimen against AECB pathogens. Methods: This was an open-label, observational, pharmacokinetic-pharmacodynamic study. Blood samples were collected at steady state at appropriate intervals. Moxifloxacin plasma concentrations were analysed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters and pharmacodynamic determinants (peak concentration [Cmax]/minimum inhibitory concentration [MIC], area under the plasma concentration-time curve during the 24-hour observational period [AUC24]/MIC, pharmacodynamic breakpoints [PDBPs]) were assessed. Results: The mean estimated pharmacokinetic parameters (Cmax 4.40 mg/L at 1.4 hours, AUC24 42.67 mg·h/L, elimination half-life 12.55 hours, total body clearance 0.16 L/h/kg) were generally similar to those observed in both young and elderly historic controls (except for higher-dose normalised Cmax and lower volume of distribution of the central compartment). Median Cmax/MIC and AUC24/MIC ratios for moxifloxacin in the fully assessable cases were, respectively, 67.5 and 823.9 against Streptococcus pneumoniae, 25 and 310.2 against Moraxella catharralis and 416.5 and 3647.5 against Haemophilus influenzae. Mean estimates of PDBP for achieving Cmax/MIC values of 12.2 and AUC24/MIC values of 125 were 0.36 and 0.35 mg/L, respectively. Conclusion: In patients with AECB the pharmacokinetic behaviour of moxifloxacin is not significantly altered by aging processes. This is consistent with moxifloxacin being metabolised mainly by means of phase II hepatic reactions, the activity of which was shown not to decline with age. Both the pharmacokinetic and pharmacodynamic analyses suggest that moxifloxacin 400 mg/day may be a valid therapeutic approach in the treatment of AECB in the elderly. Of note, the unmodified pharmacokinetic behaviour with no need for age-related dosage adjustments combined with the once-daily administration favouring compliance and the low potential for drug-drug pharmacokinetic interactions in case of polytherapy, make moxifloxacin particularly attractive in the treatment of elderly subpopulations at a very high risk of AECB. © 2006 Adis Data Information BV. All rights reserved.

Levofloxacin is considered an effective antibiotic in the treatment of community-acquired lower respiratory tract infections (LRTIs). A study was carried out on 17 in-patients to assess the pharmacokinetics of a 500 mg once-daily switch intravenous (i.v.)/oral regimen of levofloxacin in the treatment of LRTI patients. Blood samples were collected under steady-state conditions at appropriate intervals. Levofloxacin plasma concentrations were analysed by means of HPLC and pharmacokinetic parameters were estimated using the WinNonlin pharmacokinetic software package. A lower clearance of levofloxacin (2 mL/min/kg), conditioning both a longer elimination half-life (approximately 9 h) and a larger AUC(0-tau) (approximately 80 mg/L x h), was observed for both routes in our patients than in healthy volunteers. These differences may be explained considering that levofloxacin is excreted mainly as unchanged drug by the renal route, and most of our patients (71%) were very elderly subjects whose renal function physiologically declines with age. The almost complete (or =99%) absolute oral bioavailability suggests that a comparable exposure to the iv regimen may be achieved after oral administration. The overall clinical success rate was 94.1%.

An immunocompetent man developed malaise, fever, progressive weight loss, eosinophilia, and transient pulmonary infiltrates that responded to steroid treatment but recurred after its discontinuation. Examinations of feces, bronchoalveolar lavage fluid, and pulmonary tissue obtained during a 50-day period of hospitalization yielded negative results. When a new bronchoalveolar lavage sample and a new pulmonary biopsy specimen showed nematode larvae and adult worms, treatment with thiabendazole was started. However, therapy with this agent and then with mebendazole had no impact on the patient's downhill course, which ended in respiratory distress and death. Autopsy documented an overwhelming pulmonary infection with a metastrongylid nematode resembling a species of Angiostrongylus. Histologic study revealed features of necrotizing angiitis closely mimicking those of Wegener's granulomatosis. To our knowledge, this is the first reported instance of patent metastrongylid parasitism of the human pulmonary arteries with necrotizing angiitis caused by a reaction to the parasite and/or its metabolic products.