Is Roxithromycin Better than Amoxicillin in the Treatment of Acute Lower Respiratory Tract Infections in Primary Care?

,

Original Research

Is Roxithromycin Better than Amoxicillin in the Treatment of Acute Lower Respiratory Tract Infections in Primary Care?

J Fam Pract. 2002 April;51(4):329-336

By

R. M. Hopstaken, MD

A Double-Blind Randomized Controlled Trial

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References

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ABSTRACT

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 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.^1-6In 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 Legionella pneumophila, which are responsible for 1% to 50% of cases of LRTI.^14-20 Roxithromycin and the newer macrolide antibiotics are 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).

TABLE 1
CHECKLIST FOR PATIENT ELIGIBILITY

Inclusion Criteria	Exclusion Criteria
A: Age 18 years or older	Pregnant or present wish to become pregnant Breastfeeding Terminal disease Drug or alcohol abuse History of hypersensitivity to penicillins or macrolides Hospital stay in previous 4 weeks for respiratory complaints Treatment with antibiotics within preceding 14 days Treatment with any other investigational drug within 4 weeks before entry into the trial History of severely impaired hepatic or renal function Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study or evidence of uncooperative attitude Inability to attend follow-up visits Immunocompromised status Required admission to hospital Concomitant treatment with ergot alkaloids or terfenadine during the study period
AND
B: New* or increasing cough
AND
C: At least 1 of the following:
1) Shortness of breath
2) Wheezing
3) Chest pain
4) Auscultation abnormalities
AND
D: At least 1 of the following:
1) Fever (≥ 38°C)
2) Perspiring
3) Headache
4) Myalgia
AND
E: Diagnosis of LRTI according to PCP and
F: Antibiotics required (in PCP’s opinion)
* Onset within the previous 29 days.
LRTI denotes lower respiratory tract infection; PCP, primary care physician.