Cefuroxime

Vergis EN, Indorf A, File TM, et al. Azithromycin vs cefuroxime plus erythromycin for empirical treatment of community-acquired pneumonia in hospitalized patients: a prospective, randomized, multicenter trial. Arch Intern Med 2000; 160:1294-300.

* BACKGROUND The American Thoracic Society recommends a second- or third-generation cephalosporin with or without a macrolide for empiric treatment of community-acquired pneumonia (CAP) in hospitalized patients. These guidelines have resulted in better outcomes in patients younger than 60 years but not in older patients.[1] Azithromycin has demonstrated in vitro and in vivo activity against the common pathogens in CAP, including Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila, and Mycoplasma pneumoniae. This once-a-day macrolide possesses good tissue penetration and sustained tissue levels that allow for a shorter course of therapy.

* POPULATION STUDIED This multicenter study reported the results of 145 evaluable hospitalized patients with a primary diagnosis of CAP. The average age of these patients was not stated. Their condition was diagnosed by chest x-ray, with either one or more signs and symptoms consistent with lower respiratory infection or an elevated white blood cell count. Patients were excluded if they were allergic to the study drugs, had been hospitalized during the previous 14 days, were immunosuppressed, had serious renal dysfunction or conditions affecting drug absorption, or took an antibiotic within 24 hours of enrollment.

* STUDY DESIGN AND VALIDITY This was a prospective randomized unblinded trial comparing the empiric treatment of CAP with 2 regimens. One group of patients received intravenous azithromycin 500 mg daily for 2 to 5 days followed by oral therapy to complete a 7- to 10-day course. The second group was treated with the combination of intravenous cefuroxime 750 mg every 8 hours for 2 to 7 days followed by oral cefuroxime 500 mg twice a day for a complete 7- to 10-day course along with erythromycin lactobionate or base 500 mg to 1 g intravenously every 6 hours and then orally for a total of 21 days.

This study was well done, with several limitations. Concealed allocation of randomization occurred through the use of opaque envelopes after each patient was stratified by risk factors. The sample size was large enough to find a 14% difference in clinical response rates with a power of 80%. Analysis was by intention to treat. Few data (such as all-important age) were provided about the type of patients in this study, making it difficult to make generalizations. Also, the evaluators of clinical response were aware of what treatment the patient received. Given the subjective nature of the end points of "cure" versus "failure," this lack of blinding could have affected these outcome measures. However, end points such as "time to cure" (not evaluated in this study) would be more likely to be affected by observer bias.

* OUTCOMES MEASURED Clinical response (success/failure) was the primary outcome. Adverse events and in-hospital mortality were secondary end points.

* RESULTS The causative infecting organism was not known in 41% of the patients. The most common causative agents in patients with definitive or presumptive diagnoses were: S pneumonaie (19%), L pneumophila (14%), and H influenzae (13%). The rate of cure of patients with CAP was similar: azithromycin 75% (95% confidence interval [CI], 64%-84%) and cefuroxime plus erythromycin 83% (95% CI, 73%-90%). Cure rates did not differ by causative organism. Adverse effects occurred significantly more often in the cefuroxime/erythromycin-treated patients (P [is less than] .001), due in large part to catheter site reactions and gastrointestinal tract symptoms presumably related to erythromycin. Mortality was similar in the 2 groups

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RECOMMENDATIONS FOR CLINICAL PRACTICE

For the treatment of inpatient CAP, azithromycin is just as effective as the combination of cefuroxime plus erythromycin. Its favorable side effect profile and cost makes azithromycin a reasonable choice for the treatment of CAP in hospitalized patients.

REFERENCE

[1.] Gleason PP, Kapoor WN, Stone RA, et al. Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia. JAMA 1997; 278:32-39.

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