Sequential IV/PO moxifloxacin treatment of patients with severe community-acquired pneumonia.

BACKGROUND: IV/PO moxifloxacin was evaluated in the treatment of hospitalized patients with severe community-acquired pneumonia (CAP). METHODS: Data were pooled from two prospective, randomized studies. In the multinational study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD or IV/ PO amoxicillin clavulanate 1200/625 mg TID +/- IV/PO clarithromycin 500 mg BID. In the North American study, patients received 7-14 days IV/PO moxifloxacin 400 mg QD, IV/ PO alatrofloxacin/trovafloxacin 200 mg QD, or IV/PO levofloxacin 500 mg QD. The primary endpoint was clinical success at the test-to-cure visit. Severe CAP was defined according to the 1993 ATS criteria. RESULTS: In the clinically valid population, clinical success rates were 88% (167/190) for moxifloxacin- and 83% (155/186) for comparator-treated patients (95% CI = -1.9%, 12.2%). Corresponding clinical success rates for the microbiologically valid population were 87% (59/68) and 84% (54/64), respectively (95% CI = 8.6%, 15.0%). A switch from IV to PO therapy was made by day 5 of therapy for 73% of moxifloxacin- vs. 60% of comparator-treated patients (P < 0.01). Clinical success rates were similar in a retrospective analysis using the revised 2001 ATS definition of severe CAP. Mortality rates were 6% (15/241) and 10% (24/238) in the moxifloxacin and comparator treatment groups, respectively. The incidence of drug-related adverse events was similar in both treatment groups. CONCLUSION: Sequential IV/PO moxifloxacin 400 mg QD is as safe and effective as other fluoroquinolones and a beta-lactam/macrolide combination for treating hospitalized patients with severe CAP.

Dexamethasone partially protects the myometrium against beta-adrenergic agonist-induced desensitization in vivo in the rat.

OBJECTIVE: Our purpose was to determine the ability of dexamethasone to prevent the onset of myometrial desensitization to beta-adrenergic agonists in vivo. STUDY DESIGN: On day 5 post partum chronically catheterized rats were randomized to receive either dexamethasone or corn oil (vehicle), followed 12 hours later by a continuous infusion of either isoproterenol or saline solution (vehicle). Uterine contractions were monitored throughout. We measured myometrial glucocorticoid receptor levels in chronically catheterized and sham-operated rats and beta 2-adrenergic receptor densities in the experimental rats before and during the infusions. RESULTS: Surgery did not lead to any decrease in glucocorticoid receptor number. Dexamethasone significantly increased the duration of myometrial responsiveness to isoproterenol compared with vehicle-pretreated rats, although agonist-induced down-regulation of beta-adrenergic receptor number was not prevented. CONCLUSION: Dexamethasone partially protects the rat myometrium from desensitization induced by the continuous infusion of beta-adrenergic agonists through mechanisms independent of the beta 2-receptor.