Fluoroquinolones in the Management of Community-acquired Pneumonia in Primary Care

Brian Wispelwey; Katherine R Schafer

Disclosures

Expert Rev Anti Infect Ther. 2010;8(11):1259-1271. 

In This Article

Clinical Trials of Fluoroquinolones in Outpatients with CAP

Clinical trials conducted in patients with CAP treated on an outpatient basis provide relevant data for clinicians dealing with management of this common serious infection. A number of trials have been conducted with each of the three main antipneumococcal respiratory fluoroquinolones.

Gemifloxacin

In an open-label, noncomparative study, gemifloxacin (320 mg, once daily for 7 days) exhibited high clinical success rates at end-of-therapy (93.9%) and follow-up (91.7%), and high bacteriological success rates at end-of-therapy (91.7%) and follow-up (87.3%) in CAP patients treated per protocol. Slightly lower rates were seen in the intent-to-treat population. Among the 216 patients in the total CAP population, 45.8% were treated on an outpatient basis.[70]

The efficacy of gemifloxacin 320 mg once daily for 7 days was explored in patients with CAP (both inpatients and outpatients) and compared with that of trovafloxacin 200 mg daily for 7 days,[71] or that of high-dose amoxicillin/clavulanate 1 g/125 mg three-times/day for 10 days.[72] The gemifloxacin regimen proved to be clinically, bacteriologically and radiologically at least as efficacious and safe as trovafloxacin therapy or the amoxicillin/clavulanate regimen in the management of CAP.[71,72] Gemifloxacin eradicated 95.7% of S. pneumoniae, including penicillin- and macrolide-resistant strains.[72] In the intent-to-treat population, the clinical success rate at follow-up was significantly superior for gemifloxacin (87.6%) compared with trovafloxacin (81.1%; 95% CI: 0.5–12.4).[71] There were statistically fewer withdrawals due to lack of therapeutic effect in the gemifloxacin group compared with the amoxicillin/clavulanate cohort (95% CI: -8.8–0.6; p = 0.03).[72]

In a more recent trial, the efficacy and safety of gemifloxacin once daily was compared for 5 days versus 7 days for the treatment of outpatients with mild-to-moderate CAP. Gemifloxacin once daily for 5 days was not inferior to 7 days in the per protocol population with respect to efficacy and safety.[73]

Levofloxacin

A multicenter, randomized, double-blind study was conducted to compare the efficacy of levofloxacin 750 mg daily for 5 days versus levofloxacin 500 mg daily for 10 days in patients with mild-to-severe CAP.[74] Approximately 50–60% of patients were PSI classes I/II and likely treated as outpatients.[74] The high-dose, short-course levofloxacin therapy at 750 mg daily for 5 days was at least as effective and well tolerated as 500 mg per day for 10 days for treatment of CAP regardless of severity.[74]

In another randomized trial, two management strategies were explored and compared: outpatient care with oral levofloxacin therapy and hospitalization with sequential intravenous and oral levofloxacin, for treatment of patients with PSI-defined low-risk CAP.[75] Overall, successful outcome was achieved in 83.6% of outpatients and 80.7% of hospitalized patients. Additionally, more outpatients were satisfied with their overall care than hospitalized patients (91.2 vs 79.1%, respectively).[75]

In an economic evaluation of levofloxacin versus cefuroxime axetil in the treatment of outpatients with CAP, total treatment costs among patients receiving levofloxacin as initial treatment for CAP were lower than those in the group receiving oral cefuroxime axetil as initial treatment. The expected cost savings per patient in the levofloxacin group were US$169, with a mean of US$223 per patient in the sensitivity analysis. Overall, costs were 34% higher in the cefuroxime axetil group.[76]

Finally, in a retrospective claims database analysis, treatment failure rates and emergency department visits in outpatients with CAP were significantly lower in those treated with levofloxacin (500 or 750 mg) than in those treated with a macrolide (azithromycin, clarithromycin or erythromycin).[77] The greatest reduction (35%) in treatment failure was observed in the subgroup of patients aged 65 years or more, compared with the corresponding group of macrolide-treated patients. Overall, CAP-related hospitalization and costs were not significantly different between the two treatment regimens.[77]

Moxifloxacin

In a double-blind, randomized study, Torres et al. reported that oral moxifloxacin was as effective as oral standard first-line antimicrobial regimens (amoxicillin and/or clarithromycin) in the treatment of patients with CAP. Oral moxifloxacin monotherapy was better tolerated than standard therapy, and drug-related adverse event rates occurred in 20 and 31% of these groups, respectively.[78]

A large surveillance study was conducted to evaluate the efficacy, general safety and cardiac safety of moxifloxacin 400 mg in a total of 18,409 outpatients with suspected acute sinusitis, acute exacerbation of chronic bronchitis or CAP of mild-to-moderate severity.[79] Clinical cure or improvement occurred in 92.9% of the overall population, including 92.8% of those with sinusitis, 92.9% with bronchitis and 94.1% with CAP. The most common drug-related adverse events identified were nausea (5.3%), diarrhea (2.2%) and dizziness (2.0%). Importantly, no clinical evidence of increased risk of cardiac arrhythmias was observed with moxifloxacin treatment in this large patient population.[79]

Six Phase III clinical trials were conducted to evaluate the efficacy of moxifloxacin against DRSP and MDRSP in patients with CAP; in three of these studies, patients received oral moxifloxacin and were treated on an outpatient basis.[80] All patients received either oral or sequential intravenous/oral 400 mg moxifloxacin once daily for 7–14 days. Pooled analysis found an overall clinical cure rate of 95.5%. The clinical cure rate was 100% for patients with penicillin-resistant strains of S. pneumoniae, 95.7% for macrolide-resistant strains and 96.4% for MDRSP (≥three drug classes) strains.[80] The investigators concluded that moxifloxacin provided excellent clinical and bacteriological cure rates in CAP caused by DRSP.

Cost–effectiveness of empirical outpatient treatment options for CAP was assessed in France, the USA and Germany, with each country representing high, intermediate and low antimicrobial resistance prevalence, respectively.[81] Outcome measures with first-line moxifloxacin treatment, followed by co-amoxiclav if treatment failure occurred, dominated all other treatments in the three countries.[81] Moxifloxacin/co-amoxiclav was both more effective and less costly than other treatment options used in this trial.[81] A second study of cost–effectiveness was conducted in Belgium. Patients received moxifloxacin/co-amoxiclav, cefuroxime or clarithromycin as first-line treatment of CAP, followed by second-line treatment with a different antimicrobial if first-line treatment failed.[82] Moxifloxacin was more effective and less costly than the comparators. Additionally, moxifloxacin had the lowest rate of first-line treatment failure, second-line treatment, hospitalization and death.[82]

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