Safety and efficacy of sequential (IV to PO) moxifloxacin for the treatment of community-acquired pneumonia in hospitalized patients

OBJECTIVE: To evaluate the safety and efficacy of sequential IV/PO moxifloxacin (Avelox) therapy compared to IV/PO fluoroquinolone comparators for the treatment of community-acquired pneumonia (CAP) in hospitalized patients requiring initial IV therapy. METHODS: This was a prospective, randomized, double-blind, double-dummy Phase III study comparing IV/PO moxifloxacin (400/400 mg; n=249) to an IV/PO fluoroquinolone control. The initial comparator was IV alatrofloxacin/PO trovafloxacin (200/200 mg; n=80). The comparator was changed to IV/PO levofloxacin (500/500 mg; n=178) after concerns arose regarding the potential for trovafloxacin-related hepatotoxicity. The primary efficacy variable was clinical success determined at the test-of-cure visit (7-30 days post-therapy). In both phases, Day 1 and Day 3 pre- and post-infusion ECGs were taken to specifically assess cardiac safety. RESULTS: Baseline demographic characteristics were generally comparable for patients in the two treatment groups. However, more subjects in the moxifloxacin group had severe CAP (34% vs. 27%) and were categorized as having poor general health status (6% vs. 3%). The reason most cited for severe CAP was shock, which was present in 16 moxifloxacin- and 8 comparator-treated subjects. Clinical success was equivalent between treatment groups, with 88% (155 of 177) of moxifloxacin- and 89% (160 of 179) of comparator-treated subjects showing clinical cure at the test-of-cure visit (95% CI = -7.3%, 5.6%). All 7 subjects (4 moxifloxacin, 3 comparator) with penicillin-resistant Streptococcus pneumoniae isolates (MIC >2 mug/mL) from a respiratory source were clinical cures. The overall incidence of drug-related adverse events and treatment discontinuation due to adverse events were also similar for the moxifloxacin and comparator arms. Moxifloxacin was associated with a lower incidence of nausea (3% vs. 5%), headache (2% vs. 5%), injection site reaction (5% vs. 9%) and dizziness (<1% vs. 4%) than the comparators. The incidence of cardiac events was similar between groups (6% vs. 5%). Immediately after drug infusion on study Day 3, the change in QT_c with moxifloxacin was 3 +28 msec, with no evidence of QT_c prolongationrelated cardiac morbidity or mortality. CONCLUSIONS: In hospitalized patients with community-acquired pneumonia, the clinical success rates in moxifloxacin-treated patients were equivalent to the fluoroquinolone comparators despite the fact that a higher proportion of moxifloxacin-treated patients had severe pneumonia. The frequency of adverse events with the intravenous use of moxifloxacin was similar to that found with oral moxifloxacin and the fluoroquinolone comparators.