Is roxithromycin better than amoxicillin in the treatment of acute lower respiratory tract infections in primary care? A double-blind randomized controlled trial - Original Research

Journal of Family Practice, April, 2002 by R.M. Hopstaken, P. Nelemans, E.E. Stobberingh, Muris J.W.M., P.E.L.M. Rinkens, G.J. Dinant

* OBJECTIVE To assess the efficacy of roxithromycin relative to amoxicillin.

* STUDY DESIGN We conducted a double-blind randomized controlled trial of oral 500 mg amoxicillin 3 times per day vs oral 300 mg roxithromycin once a day for 10 days.

* POPULATION We included 196 adults who had presented to a general practitioner with lower respiratory tract infection (LRTI) and, in the physician's opinion, needed antibiotic treatment.

* OUTCOMES MEASURED We measured clinical response after 10 and 28 days, defined in 4 ways: (1) decrease in LRTI symptoms; (2) complete absence of symptoms; (3) decrease in signs; and (4) complete absence of signs. Self-reported response included the decrease in symptoms and the time until resumption of impaired or abandoned daily activities on days 1 through 10, 21, and 27.

* RESULTS Clinical cure rates after the completion of antibiotic treatment (10 days) were not significantly different for the 2 groups. After 28 days, the roxithromycin group showed no increase in cure rate as evidenced by the decrease in symptoms, indicating a significantly lower cure rate. However, this difference did not alter physicians' overall conclusion after complete follow-up that 90% of patients, regardless of age, had been effectively treated with either amoxicillin or roxithromycin.

* CONCLUSIONS The surplus value of roxithromycin was not confirmed. Amoxicillin remains a reliable first-choice antibiotic in the treatment of LRTI in general practice.

* KEY WORDS Respiratory tract infections; bronchitis; pneumonia; antibiotics; family practice. (J Fam Pract 2002; 51:329-336)

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KEY POINTS FOR CLINICIANS

* Amoxicillin and roxithromycin are equally effective in the treatment of patients presenting with lower respiratory tract infections and needing antibiotic treatment.

* Most patients remain symptomatic after 10 days of treatment with either drug.

* The low incidence of atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae) in the Netherlands minimizes the potentially greater surplus value of macrolide antibiotics over amoxicillin.

Acute community-acquired lower respiratory tract infections (LRTIs) in adults include acute bronchitis, pneumonia, and infectious episodes in patients with asthma or chronic obstructive pulmonary disease (COPD). In acute bronchitis and exacerbations of COPD, the value of antibiotic therapy is doubtful; in pneumonia, however, it is widely accepted. Because distinguishing between these disease entities on clinical grounds alone is often impossible, deciding which patients would benefit from antibiotic treatment remains difficult. (1-6) In the Netherlands, as in the United States and Great Britain, antibiotics are prescribed for patients with acute bronchitis approximately 80% of the time. (7-9)

If a primary care physician (PCP) decides to treat LRTI with antibiotics, amoxicillin is the drug of first choice in the Netherlands. (10-13) However, amoxicillin is not effective in infections caused by atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legoinella pneumophila, which are responsible for 1% to 50% of cases of LRTI. (14-20) Roxithromycin and the newer macrolide antibiotics am recommended as drugs of choice for the empirical treatment of community-acquired pneumonia in low-risk patients in the United States and Canada (21-23) because those drugs cover both typical and atypical pathogens. Amoxicillin has long proved to be a reliable drug and one to which the resistance of common respiratory tract pathogens (Streptococcus pneumoniae and Haemophilus influenzae) in the Netherlands is low. (24-29)

Community-based studies that evaluate treatment for LRTI are lacking. Also lacking are independent randomized controlled studies comparing amoxicillin with roxithromycin or other new macrolides for LRTI. Our double-blind randomized trial attempted to determine whether the preference for amoxicillin in the Netherlands is well founded. In the trial, patients with LRTI who in their PCP's opinion needed antibiotic treatment were assigned to either amoxicillin or roxithromycin. We then compared the efficacy and safety of both drugs.

METHODS

Eligibility Criteria and Baseline Characteristics

Eligible study subjects were patients in the southern part of the Netherlands who presented with signs and symptoms of LRTI that their PCPs believed warranted antibiotic therapy. Table 1 lists the inclusion and exclusion criteria.

Baseline data (at day 1) were obtained to evaluate the comparability of prognostic factors between the intervention groups. The PCP performed an extensive medical history and physical examination. In addition, a sputum sample, oral washing, and nasopharyngeal swab were taken for bacteriologic examination. Venous blood samples were taken for blood chemistry, hematology, and serology (initial titers of the viral pathogens M pneumoniae and L pneumophila).

Interventions

Once the samples had been collected, patients were randomly assigned to oral treatment with either 500 mg amoxicillin 3 times daily for 10 days or 300 nag roxithromycin once daily for 10 days. A computer program using random permuted blocks of 6 prepared a randomization list for each participating center. Batches of drug packages, each provided with a unique trial code, had been sent in advance to the participating general practices. A double-dummy technique achieved blinding of patients, treating physicians, and investigators to the assigned medication. This was necessary because amoxicillin and roxithromycin have different dosing schedules (3 times a day versus once daily) and are not identical in appearance (capsule versus tablet). All capsules and tablets had identical appearance and taste. All patients received both forms of their assigned medication. Compliance with medication regimens was measured by Medical Event Monitoring Systems (MEMS), an electronic recording system that compiles the dosing history of ambulatory patients taking oral medication."