Cephalexin and amoxicillin

Adult patients (?18 years of age) presenting with CAP of suspected pneumococcal origin were enrolled in the study.

Patients were classified as having CAP if they presented with fever (rectal temperature >38.5?C or oral temperature >38.0?C), radiologic evidence of pneumonia, and at least one of the following signs or symptoms: purulent sputum, dyspnea/tachypnea (>20 breaths/min), and/or auscultatory findings indicative of pulmonary consolidation. The etiology was suspected of being pneumococcal if the patient presented with at least 1 of the following findings: rapid onset of symptoms (?48 hours), high fever (rectal temperature ?39°C, or oral temperature ?38.5°C) accompanied by rigors or chills, pleuritic chest pain, chest radiograph showing an infiltrate, or the presence of Gram-positive cocci on direct sputum stain. Patients were excluded from the study if they presented with a history of hypersensitivity to quinolones or penicillins, prior history of tendinopathy associated with quinolones, or suspected aspiration pneumonia. Patients were not admitted if they had a serious respiratory infection requiring parenteral therapy or mechanical ventilation, a concurrent disease considered likely to interfere with the clinical course of the pneumonia, or neutropenia (neutrophil count 3.0 mg/dL [>265 µmol/L]), hepatic disease (baseline alanine aminotransferase or aspartate aminotransferase and/or total bilirubin level more than 3 times the upper limit of normal), serious heart failure, or a life-threatening disease and life expectation of 48 hours before the onset of pneumonia were not eligible for entry into the study. Also excluded were patients who had received a systemic

antibiotic

Adverse events were recorded at every visit, and were classified by the investigator as to their severity and relationship to the medication being studied. Two blood samples were obtained for cultures from each patient before treatment was started. At visit 1, samples of bronchopulmonary secretions were also collected for culture.

A sample of sputum or bronchial material was obtained by 1 of the following methods: bronchoalveolar lavage (BAL) or protected specimen brush in a telescoping catheter, transtracheal aspirate, or pleural fluid by aspiration of the effusion.

Gram's stains were performed on all sputum samples and all bronchial specimens.

The quality of the sputum and of the nasotracheal and endotracheal aspirates was evaluated cytologically using a low power lens (100x) and only samples with >25 leukocytes and 6 colony forming units (cfu) per mL was required to distinguish the microorganisms considered to be causing the pneumonia from contaminants.

The quantitative cut point for the evaluation of the cultures obtained by expectoration and transtracheal aspirate was 10 6 cfu/mL.

The cut points for BAL and protected brush specimens were 10 4 cfu/mL and 10 3 cfu/mL, respectively.

Antibiotic susceptibility (minimum inhibitory concentration values [MIC]-90) was determined for Gram-positive and Gram-negative pathogens using the E-test (AB biodisk: Solna, Sweden) for both moxifloxacin and amoxicillin as well as for clarithromycin, cefuroxime, and clavulanic amoxicillin-acid. Blood and urine samples were collected at visit 1 for detection of the pneumococcal antigen by counterimmuno-electrophoresis.

Blood samples for

serological

All the serological tests were carried out at a centralized reference laboratory (Glarif Cerba, Baillet en France, France). All the patients who were enrolled in the study and received at least 1 dose of the study medication were evaluated as patients with intention to treat (ITT population). Patients who were given the study medication for a minimum of 48 hours (in the case of clinical failure) or 5 full days (in the case of clinical success) were included in the evaluable population (EP).

Efficacy analyses were performed on both populations.

The primary efficacy variable was clinical response 3 to 5 days after completion of treatment (visit 3).

The patient was considered to be cured when the acute signs and symptoms related to the infection had disappeared, or had improved so much that the patient no longer required additional or alternative antibiotic therapy. Treatment was considered a failure when there was an insufficient reduction of the signs and symptoms of infection such that the patient required additional or alternative antibiotic therapy or died as a consequence of the primary diagnosis (pneumonia). The outcome was classified as undetermined when clinical assessment was not possible (premature withdrawal after less than 2 days of treatment, patient unavailable for evaluation, etc). The early failures (at visit 2) were also classified as failures at visits 3 and 4, and the failures at visit 3 were also considered failures at visit 4.

Clinical success was defined as cure in both the evaluable and the ITT populations.

Clinical failure in the EP was defined as a failure or relapse (initial or partial resolution of clinical signs and symptoms during the study, but with subsequent recurrence of the clinical condition making further antibiotic therapy necessary within 21 to 28 days after the period of administration of the study drug).

Clinical failure in the ITT population was defined as failure/relapse, undetermined, or missing efficacy data. Patients for whom at least 1 pathogen was identified in an acceptable pretreatment culture and who had a valid post-treatment bacteriological evaluation were included in the population of microbiologically valid patients. Infection was also considered to be documented when a pathogen was detected in blood culture, or the pneumococcal antigen was found in the patient's serum or urine, especially if this was associated with a positive culture. In the case of atypical pathogens, infection was considered present if there was a fourfold rise in antibody titers or a value of >64 in the case of L pneumophila , or a single titer immunoglobulin M of >8 for M pneumoniae using immunofluorescence assay, immunoglobulin G of >128 for L pneumophila and C Pneumoniae , or >64 for M pneumoniae . The bacteriological response was classified as eradication (initial pathogen absent during or after treatment), presumed eradication (sampling rendered impossible owing to clinical improvements which made the production of sputum impossible), persistence (repeat isolation of the pathogen during or after completion of treatment), presumed persistence (clinical failure without control culture) or superinfection (isolation of a new pathogen during or after completion of treatment, associated with a recurrence of the clinical signs and a new radiologic infiltrate). Bacteriological success at the end of treatment (visit 3) and on follow up (visit 4) prednisone and amoxicillin together was defined as eradication or presumed eradication.

Bacteriological failure at visit 3 was defined as persistence, presumed persistence or superinfection and at visit 4 as persistence, presumed persistence, eradication with reinfection (eradication of the initial causal pathogen at visit 3, but with isolation of a new pathogen before visit 4 associated with a clinical relapse) or eradication with recurrence (eradication of the initial causal pathogen on visit 3, but isolation of the same pathogen before or at visit 4 associated with clinical relapse).