Community-acquired pneumonia is frequently encountered in the United States and throughout the world. It is often difficult to distinguish clinically between a bacterial and a nonbacterial etiology of community-acquired pneumonia. Even in patients believed to have bacterial pneumonia, identifying the specific pathogen is only possible in 30 percent of cases or fewer. Consequently, treatment with antimicrobial agents is usually empiric, based on the most commonly encountered pathogens and the age of the patient. A variety of antibiotics is used to treat community-acquired pneumonia, although typically a second-generation cephalosporin, with or without a macrolide, is selected. Moola and colleagues conducted a large multicenter trial to evaluate the efficacy of clarithromycin, a second-generation macrolide, with grepafloxacin, a broad-spectrum quinolone antibiotic with activity against gram-positive, gram-negative and atypical pathogens (i.e., Chlamydia, Mycoplasma and Legionella species).
The trial was a double-blind, randomized prospective study that included adult patients with a radiologically confirmed diagnosis of pneumonia. Additional entry criteria were pleuritic chest pain, fever of at least 38°C (101°F) or higher, cough and auscultatory findings such as rales or evidence of consolidation. Excluded were patients with a history of carcinoma, empyema, lung abscess, severe asthma or immunocompromise. The patients were randomized to receive 500 mg of oral clarithromycin twice daily or 600 mg of oral grepafloxacin daily for 10 days. All patients received concurrent placebo pills that appeared identical.
Patients were assessed at study entry, when blood and sputum cultures were obtained. In addition, serologic testing for Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila was performed. Follow-up evaluations were done on days 4 to 6 after the start of treatment, one to three days after completion of the antibiotics and again at 28 to 35 days post-treatment. The primary outcomes measured were clinical and radiographic responses at the follow-up visits. These outcomes were assessed for all patients, regardless of whether a pathogen was identified.
Of 504 patients initially recruited, 251 were randomized to receive grepafloxacin, and 253 were given clarithromycin. The mean age of the patients was 48 years, and about one fourth were older than 65 years of age. Radiographic findings and severity of symptoms were the same in both groups of patients. Fifty-seven percent were initially admitted to the hospital, and the remainder were treated as outpatients. There were 174 patients unavailable for complete follow-up; the authors analyzed their data on an observed and intention-to-treat basis.
Of the 330 patients who completed the follow-up evaluations, 90 percent of the grepafloxacin group and 89 percent of the clarithromycin group had a satisfactory clinical response. Patients less than 65 years of age had response rates of 93 and 92 percent compared with rates of 81 and 74 percent among older patients. The overall response numbers in the intention-to-treat populations were 75 and 76 percent, respectively. A pretreatment pathogen was identified in 26 percent of patients, with S. pneumoniae causing 22 percent and M. pneumoniae causing 25 percent of the identifiable infections. The overall clinical success rate for patients in whom a pathogen was identified was 92 percent for both antibiotics. In evaluating radiographic response, improvement was noted in 80 percent of the grepafloxacin patients and in 76 percent of those who received clarithromycin. Of patients known to be infected with one of the three atypical pathogens, 100 percent responded to grepafloxacin and 88 percent to clarithromycin. The most common adverse events were abnormal taste, nausea and diarrhea.
The authors conclude from this study that grepafloxacin and clarithromycin are effective in the treatment of community-acquired pneumonia. The first agent offers some advantage in that it can be given once daily and may be a more effective choice in older patients.