Efficacy and safety of sequential IV/PO moxifloxacin for the treatment of severe community-acquired pneumonia

Background

The oral form of moxifloxacin (MXF) has been used in 9 million patients and has been demonstrated to be an effective and well tolerated treatment for respiratory tract infections in extensive clinical trials. An IV formulation of MXF has been developed and recently was approved in the US for the treatment of community-acquired pneumonia, acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and uncomplicated skin and skin structure infections. The efficacy and safety of IV/PO MXF compared with IV/PO comparator (CMP) in CAP was examined in two randomized, controlled studies; a pooled analysis of the patients with severe CAP is reported here.

Methods

In both studies, MXF-treated patients received 7–14 days IV/PO MXF 400 mg QD. In study 1, CMP-treated patients received IV/PO alatrofloxacin/trovafloxacin 200 mg QD or IV/PO levofloxacin 500 mg QD; in study 2, CMP-treated patients received IV/PO amoxicillin clavulanate 1200/625 mg TID ± IV/PO clarithromycin 500 mg BID. Severe CAP was defined as the presence of at least one of the following conditions: respiratory rate >30 breaths/min; P_aO₂/FIO₂ ratio < 250 mmHg or PO₂ ≤ 8 kPa (60 mmHg); requirement for mechanical ventilation; chest radiograph indicating bilateral or multilobe involvement; increase in the size of opacity by ≥ 50% within 48 hours of admission; or shock (systolic blood pressure <90 mmHg or diastolic pressure <60 mmHg).

Results

One hundred and ninety MXF-treated and 186 CMP-treated patients comprised the clinically valid population. Treatment groups were similar with respect to demographic and baseline medical characteristics. Bilateral or multilobar involvement was present in 44% of MXF-treated and 54% of CMP-treated patients, and was the most common reason for categorizing CAP as severe. Clinical resolution was achieved in 88% (167/190) of MXF-treated and 83% (155/186) of CMP-treated patients (95% CI = -1.9%, 12.2%). A switch from IV to PO therapy was made by day 5 of therapy for 73% (139/190) of MXF-treated vs 60% (112/186) of CMP-treated patients (P < 0.01). Similar durations of therapy and time of IV to PO switch were observed for the ITT and microbiologically valid populations. Serious drug-related adverse events occurred in 7% (16/241) of MXF-treated and 6% (14/238) of CMP-treated patients.

Conclusions

Sequential IV/PO MXF is as effective as the standard IV/PO fluoroquinolone or IV/PO beta-lactam/beta-lactamase inhibitor ± macrolide regimens for the treatment of severe CAP. IV/PO MXF is an excellent choice for empiric therapy of severe CAP.