The efficacy of cefditoren pivoxil in the treatment of lower respiratory tract infections, with a focus on the per-pathogen bacteriologic response in infections caused by Streptococcus pneumoniae and Haemophilus influenzae: a pooled analysis of seven clinical trials.

BACKGROUND

Community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are frequently caused by Streptococcus pneumoniae, Haemopbilus influenzae, and Moraxella catarrbalis; thus, these are the target pathogens for antibiotic treatment.

OBJECTIVES

This pooled analysis was performed to evaluate the efficacy of cefditoren pivoxil (CDN) in patients with lower respiratory tract infections (CAP or AECB). A particular focus was the per-pathogen bacteriologic response rate among the most common causative pathogens, S pneumoniae, H influenzae, and M catarrbalis.

METHODS

The final reports of all clinical trials of CDN in the treatment of community-acquired lower respiratory tract infection were reviewed. Microbiologic outcome data for CDN 200 and 400 mg and comparator treatments were pooled from 4 CAP studies (3 randomized and 1 noncomparative) and 3 AECB studies. The comparators were the standard oral treatments clarithromycin 500 mg BID, cefuroxime 250 mg BID, cefpodoxime 200 mg BID, and amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID. Microbiologic response was defined as eradication of the initial pathogen or presumed eradication (absence of sputum for culture in a patient with a clinical response).

RESULTS

The bacteriologically evaluable population contained 654 patients in the CDN 200-mg group, 592 in the CDN 400-mg group, and 664 in the comparator group. A total of 1223 target pathogens were isolated before treatment: 406 isolates of S pneumoniae (including 56 penicillin-nonsusceptible [intermediate + resistant] strains), 595 isolates of H influenzae, and 222 isolates of M catarrbalis. The microbiologic response ranged from 84.1% to 88.8% in the CAP studies and from 75.1% to 77.1% in the AECB studies, with no differences between the CDN 200-mg, CDN 400-mg, and comparator groups. In the analysis of per-pathogen bacteriologic response, similar response rates were found for S pneumoniae (range, 88.5%-92.0%), H influenzae (range, 82.7%-86.6%), and M catarrbalis (range, 84.1%-95.2%), with no significant differences between groups. Focusing on penicillin-nonsusceptible (MIC >or=0.12 microg/mL) strains of S pneumoniae, CDN (both doses pooled) was associated with a response rate of 92.3% (36/39 isolates); all nonresponders were in the CDN 200-mg group. When only penicillin-resistant (MIC >or=2 microg/mL) strains were considered, there was only 1 nonresponder, again in the CDN 200-mg group. Thus, the overall response rate to CDN (both doses pooled) was 94.4% (17/18 isolates).

CONCLUSIONS

In this pooled analysis, CDN was associated with high rates of per-pathogen bacteriologic response among the main causative pathogens in lower respiratory tract infection. The rates of response were approximately 85% against H influenzae and approximately 90% against S pneumoniae, including penicillin-intermediate and penicillin-resistant strains.