Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections

John P. A. Ioannidisa,b, Despina G. Contopoulos-Ioannidisa,c, Priscilla Chewb and Joseph Laub,*

a Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece; b Division of Clinical Care Research, New England Medical Center, Department of Medicine, Tufts University School of Medicine, 750 Washington Street, Box 63, Boston, MA 02111; c Department of Pediatrics, George Washington University School of Medicine, Washington, DC 20010, USA


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We carried out a meta-analysis of randomized controlled trials comparing 3–5 days of azithromycin with other antibiotics that are typically given in longer courses for the treatment of upper respiratory tract infections. For acute otitis media (19 comparisons including 3421 patients), acute sinusitis (11 comparisons including 1742 patients) and acute pharyngitis (16 comparisons including 2447 patients), azithromycin had similar clinical failure rates to the other antibiotics [random effects odds ratios 1.12, 95% confidence interval (CI) 0.81–1.54; 0.91, 95% CI 0.60–1.39; and 1.07, 95% CI 0.59–1.94, respectively]. The difference in clinical failures was <0.5%, and no 95% CIs exceeded 2.0%. There was no heterogeneity between studies. Subtle differences between comparators could have been due to chance. There were no significant differences in bacteriological outcomes. Azithromycin was discontinued because of adverse events in only 37 of 4870 (0.8%) patients. Short courses of azithromycin are as effective as longer courses of other antibiotics for upper respiratory tract infections. Convenience of dosing should be balanced against the increased cost of this regimen for the treatment of these common infections, where often no antibiotic may be indicated at all.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Azithromycin is active against most common upper respiratory bacterial pathogens such as group A streptococci, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.1 Its convenient, short-course dosing in 3–5 day regimens has led to increased use in the community. Azithromycin differs from other commonly used macrolides such as erythromycin, clarithromycin, roxithromycin and dirithromycin in its short treatment course. However, the exact role of azithromycin in the treatment of acute upper respiratory tract infections, including acute pharyngitis, acute sinusitis and acute otitis media, remains unclear.

For all of these conditions, other, less expensive generic antibiotics are available that provide satisfactory antimicrobial coverage. Moreover, many of these infections are caused by viral pathogens and resolve spontaneously without any antibiotics.2 Therefore, investigators have challenged whether antibiotics may be needed at all, especially in cases of acute sinusitis3,4 and acute otitis media.5–7 Even when antibiotics are given, the optimal duration of treatment for these conditions is uncertain. There is accumulating evidence that short-term courses may be appropriate treatment for acute sinusitis8 and acute otitis media,9–13 whereas short-term courses have been advocated even for acute pharyngitis.14

A large number of trials have been carried out in the last decade, comparing short courses of azithromycin with longer courses of traditional antibiotics for these common infections. As in the case of lower respiratory tract infections, which are evaluated in a companion meta-analysis,15 the small number of patients in each trial precludes any firm conclusion about the relative efficacy and safety of azithromycin in these settings. A formal meta-analysis was thus carried out to compare azithromycin with other antibiotics that typically require longer treatment courses.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Literature search and eligibility of trials

We carried out a literature search of the MEDLINE and EMBASE databases for pertinent randomized controlled trials (RCTs) published from 1990 up to 21 March 2000. We used the text word and the medical subject heading term ‘azithromycin’. We included trials that assessed the use of azithromycin in the treatment of acute otitis media, acute sinusitis and acute pharyngitis (including tonsillitis or pharyngo-tonsillitis). We also examined the Cochrane Controlled Trials Registry for additional trials, but none was found.

Eligible for the meta-analysis were all RCTs reporting clinical efficacy data for azithromycin and comparator antibiotics for at least one of the study conditions mentioned above, with more than 10 patients per treatment arm. Trials of chronic otitis media and chronic sinusitis were excluded.

We accepted RCTs published in English, French, German or Spanish. Other languages were also considered if an English abstract provided sufficient information for the meta-analysis. All age groups qualified for the meta-analysis. The inclusion criteria and validity of the studies were independently determined by two investigators.

We avoided inclusion of abstracts, as they were likely to contain incomplete information, whereas inclusion of data on file might be biased, as they would have been provided from the manufacturer of azithromycin. Clinical research on antibiotics is a field where some trials may remain unpublished. Nevertheless, it is unclear whether such unpublished studies may affect the comparisons of this meta-analysis, as biases may operate in favour of azithromycin or in favour of the comparators depending on sponsorship or other factors.

Primary outcome

The primary outcome was the clinical failure rate in the group of patients treated with azithromycin versus the comparator antibiotic. We selected as time for evaluation of the clinical outcome the day closest to day 10, as all studies carried out primary outcome evaluations between days 7 and 15. Day 10 is the time-point used by the majority of trials. Relapses at the time of clinical evaluation were included with failures. Data on bacteriological failures among culture-positive cases were also collected.

Data extraction

From each trial report (and separately for each condition of interest), we extracted information on the year and language of publication, the number of centres and their location, company sponsorship of the study, inclusion and exclusion criteria, definition of the conditions of interest, antibiotics used (class, dose and duration), patient demographics (mean age and gender), number of patients allocated per treatment arm, number of patients eligible for the efficacy analysis, clinical and bacteriological failure rates and the day(s) of outcome evaluation. For each treatment arm, we extracted data on discontinuations due to toxicity and severe-grade side effects, when available. Finally, we also extracted information about the study design (method of random allocation, adequacy of allocation concealment and masking).

Statistical analysis

We calculated pooled odds ratios, risk ratios and risk differences and their 95% confidence intervals (CIs) for clinical failures for each upper respiratory tract infection of interest. Between-study heterogeneity was assessed using the {chi}2-based Q statistic.16 We used both the Mantel– Haenszel fixed effects17 and DerSimonian–Laird random effects18 models. In general, the two models give the same estimate when there is no between-study heterogeneity. The random effects model is more conservative and yields wider CIs, when between-study heterogeneity is present.16 For evaluation of toxicity, we pooled and compared rates of discontinuations due to side effects for azithromycin and each comparator antibiotic across all cases of upper respiratory tract infection. In the main analysis, study-specific rates were weighted simply by the sample size of each study. Weighting by the inverse of the fixed or random effects variance yielded similar results (not shown).

Subgroup analyses were carried out to evaluate differences in comparative efficacy when different comparator antibiotics were used. Bias diagnostics were also employed including (i) inverse funnel plots, to evaluate whether the treatment effect depends on the trial sample size (suggestive of publication bias);16 (ii) recursive cumulative meta-analysis, to evaluate whether the treatment effect changes asymmetrically in the same direction over time19 and (iii) control-rate meta-regression, to evaluate whether the treatment effect (odds ratio) depends on the rate of clinical failure in the comparator antibiotic arm.20

Analyses were conducted in Meta-Analyst (Joseph Lau, Boston, MA, USA) and in SPSS version 9.0 (SPSS Inc., Chicago, IL, USA). All P values are two-tailed.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Eligible and excluded studies

The literature search identified 45 independent studies21–65 that were pertinent for the conditions of interest. Three trials24,35,54 had three study arms, resulting in a total of 48 comparisons. In all cases where azithromycin was compared with a different antibiotic, the comparator antibiotic was administered for a longer course.

Thirty-seven trials studied only one condition of interest; nine trials24,35–37,43,48,51–53 studied more than one condition of interest. Articles that studied more than one condition were evaluated for eligibility for each condition separately.

Twelve studies were excluded, because clinical outcomes were not given separately for each specific upper respiratory tract infection (n = 3);35,37,48 only different azithromycin doses were compared (n = 1);36 the comparator was placebo and not another antibiotic (n = 1);40 there were fewer than 10 patients in each treatment arm (n = 1);37 or clinical outcomes were not given per treatment arm (n = 1),32 non-relevant clinical outcomes were provided (n = 3)25,38,46 or clinical outcome data were absent (n = 2).43,61 One study24 was excluded from the analysis of acute pharyngitis and acute sinusitis, but was eligible for the analysis of acute otitis media.

Acute otitis media

A total of 25 independent studies were identified. One study24 had three treatment arms and, therefore, there were a total of 26 comparisons. Seven studies (seven comparisons) were excluded from the meta-analysis, because different azithromycin doses only were compared (n = 1);36 no separate outcome data for acute otitis media patients were provided (n = 2, 31 patients);37,48 clinical outcomes were not given per treatment arm (n = 1, 123 patients);32 no relevant clinical outcomes were provided (n = 1);38 or clinical outcomes were absent (n = 2).43,61 In total, 154 patients with relevant outcome data and acute otitis media had to be excluded from the data synthesis.

The 18 eligible studies (19 comparisons) including 3421 patients were all published between 1992 and 2000, and in the English language, except for one24 in Spanish. There were 13 multicentre studies. Four studies were conducted in the USA, seven in Europe, three in South American countries and four in more than one continent. Four trials were sponsored by Pfizer,21,22,31,33 two by another pharmaceutical company32,59 and the remaining 12 studies did not state their source of funding. With three exceptions,51–53 studies were conducted in children. The mean age of children ranged from 11 months to 6 years. The percentage of males ranged from 45% to 62% (Table 1Go).


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Table 1. Characteristics of eligible acute otitis media studies
 
Fourteen studies used typical clinical signs and symptoms for the diagnosis of acute otitis media (Table 1Go). These included fever, ear pain, pulling on the ear, lethargy, irritability, erythema, yellow or white discolouration of the tympanic membrane, fullness or bulging of the tympanic membrane, decreased light reflex and decreased tympanic mobility per pneumatic otoscopy. Five studies32,53,57,59,60 specifically included patients with acute tympanic perforation and three studies31,45,49 excluded these patients. Tympanocentesis was elective or required for all patients in six studies.21–23,31,33,57 Patients with either acute or recurrent otitis media were included in two studies.50,58

Thirteen studies used a 3 day azithromycin regimen. Five studies23,30,45,49,59 used a 5 day regimen. Among the 19 eligible comparisons, the comparator drugs were co-amoxiclav (n = 10), cefaclor (n = 4), clarithromycin (n = 3), roxithromycin (n = 1) and amoxicillin (n = 1). Comparators were typically given for 10 days, with the exception of one study59 where clarithromycin was also given only for 5 days. Exclusion of this study did not alter the results.

The randomization method was described in detail in only two studies.21,22 The efforts for allocation concealment were not clarified in any of the studies. There were 16 open-label studies, one single blind study30 and one double blind study.49

The total number of evaluable patients in the 19 eligible comparisons was 3421; sample size ranged from 30 to 553 patients. In all studies the outcome evaluation was carried out at between 7 and 14 days. Overall, there were 132 clinical failures in 1754 (7.5%) evaluable patients in the azithromycin treatment arm versus 112 clinical failures in 1667 (6.8%) evaluable patients in the comparator arms. There was no significant heterogeneity between the studies. The pooled estimates showed no difference between azithromycin and its comparators (Figure 1Go). The results were similar with the fixed and random effects models. Data on bacteriological failure were available for 399 isolates in five studies and also showed that azithromycin was no better than its comparators (random effects odds ratio 1.74; 95% CI, 0.71–4.31), but there was evidence of between-study heterogeneity (P = 0.05).



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Figure 1. Meta-analysis of clinical failures of azithromycin versus comparator antibiotics for acute otitis media. Each study is shown by author name, number of patients, point estimate and 95% CI of odds ratio and comparator antibiotic used. Also shown are the pooled odds ratio and 95% CI by random effects calculations.

 
Acute sinusitis

A total of 15 independent studies were identified. There were two studies24,35 with two RCTs reported in each; therefore, there were a total of 17 comparisons. Five studies (six comparisons) were excluded from the analysis, because they had fewer than 10 patients per treatment arm (n = three studies; four comparisons, 44 patients);24,37,48 they simply compared azithromycin at different doses (n = 1);36 or with a placebo (n = 1).40

The 10 eligible studies (11 comparisons; Table 2Go) were published between 1991 and 1999, in the English language except for one study in Russian44 and another in Portuguese.29 Seven were conducted exclusively in Europe, one in the USA, one in Russia and one in Brazil. Five studies26,27,29,35,41 were sponsored by Pfizer; the other five studies did not state their source of funding. Studies were conducted in adults. The mean age of the study population ranged from 30 to 40 years and the percentage of males ranged from 34% to 89%.


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Table 2. Characteristics of the eligible acute sinusitis studies
 
Diagnostic criteria varied between studies (Table 2Go). The signs and symptoms used for the diagnosis of acute sinusitis were described in detail in three studies.29,41,53 Six studies required a diagnostic sinus radiograph. One study also required sinus computed tomography. Two studies also required nasal endoscopy to confirm the presence of purulent discharge from the ostium or complete obstruction of the osteomeatal complex. Two studies required sinus aspirate culture to confirm the diagnosis, which was elective in another study. Eight studies used a 3 day azithromycin regimen and two studies26,35 used a 5 day regimen. The comparator drugs were amoxicillin (n = 3), co-amoxiclav (n = 3), erythromycin (n = 1), cefaclor (n = 1), clarithromycin (n = 1), roxithromycin (n = 1) and penicillin (n = 1). Comparator antibiotics were prescribed for 10 days, with one exception29 where the course lasted for 14 days.

Three studies26,35,41 described the randomization method in detail. The effort for allocation concealment was not clearly stated in any of the studies. There were six open-label studies, one single blind study26 and one double blind study.41 Two studies35,44 did not comment on masking.

The total number of evaluable patients in the 11 eligible comparisons was 1742; trial sample size ranged from 78 to 434 patients with acute sinusitis. In all studies outcomes were evaluated between days 10 and 15. Overall, there were 55 clinical failures in 912 (6%) evaluable patients in the azithromycin group and 52 clinical failures in 830 (6.3%) evaluable patients in the comparator arms (random effects odds ratio 0.91; 95% CI 0.60–1.39). The pooled estimates show no difference between azithromycin and its comparators (Figure 2Go). Of interest, all four trials favouring azithromycin were sponsored by Pfizer. The results were similar with the fixed and random effects models. Bacteriological data based on sinus puncture and aspirate were too limited to allow useful inferences on bacteriological failures.



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Figure 2. Meta-analysis of clinical failures of azithromycin versus comparator antibiotics for acute sinusitis. Each study is shown by author name, number of patients, point estimate and 95% CI of odds ratio and comparator antibiotic used. Also shown are the pooled odds ratio and 95% CI by random effects calculations.

 
Acute pharyngitis

Twenty-one studies were identified with 24 pertinent comparisons. Seven studies were excluded, because the clinical outcomes were not given for each type of upper respiratory tract infection (n = 3),35,37,48 the study arms compared different azithromycin treatment schedules (n = 1),36 no data were provided on the clinical outcome of interest (n = 2, one having three study arms)26,45 or no clinical outcomes were described at all (n = 1).43 In total, 177 patients with relevant outcomes and group A streptococcal pharyngitis, treated with azithromycin or a comparator antibiotic, were excluded from the analysis.

Fourteen studies were eligible for the quantitative data synthesis. Two studies24,54 had three treatment arms, thus 16 independent comparisons were included. From the 14 eligible studies published between 1991 and 1998 (Table 3Go), 12 (14 comparisons) were in the English language, one in Spanish24 and another in Turkish.34 There were nine multicentre studies. Ten studies were conducted exclusively in Europe, one in the USA, one in Mexico, one in Turkey and another in Australia. Source of funding was not stated, with two exceptions,42,63 which were sponsored by Pfizer. There were four adult studies42,51,52,54 and 10 paediatric studies with the mean age ranging from 5 to 7 years. The percentage of males ranged from 42% to 60%.


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Table 3. Characteristics of the eligible pharyngitis studies
 
All studies required confirmation of the diagnosis of S. pyogenes pharyngotonsillitis by a rapid test or a positive throat culture. Patients who did not have S. pyogenes isolated from the baseline culture were dropped from all subsequent analyses. Fourteen comparisons used a typical 3 day azithromycin regimen, one comparison54 used a high azithromycin dose (20 mg/kg/day) for 3 days and only one study42 used a 5 day azithromycin regimen. In the 16 eligible comparisons the comparator drugs were penicillin V (n = 7), clarithromycin (n = 3), cefaclor (n = 3), erythromycin (n = 1), roxithromycin (n = 1) and co-amoxiclav (n = 1). The comparator antibiotics were typically prescribed for 10 days (7–14 days in one study).24

The randomization method was stated in only three studies.42,55,63 All the studies were open-label except for one double blind study54 and one single blind study.64 Efforts for allocation concealment were not clearly stated in any of the studies.

The total number of evaluable patients in the 16 eligible comparisons was 2447. The largest study had 358 patients. The largest sample size in a comparison was 255. In all studies outcome evaluation was carried out at around day 10 (9–15 days).

Overall there were 64 clinical failures in 1302 (4.9%) evaluable patients treated with azithromycin and 49 clinical failures in 1145 (4.3%) evaluable patients in the comparator arms. There was no evidence of differing efficacy between azithromycin and comparator agents. There was no significant heterogeneity between the comparisons. Data on bacteriological failure were available for 2335 isolates in 14 comparisons and the random effects odds ratio was 1.19 (95% CI 0.64–2.22), but there was large heterogeneity between studies (P < 0.01).

Summary estimates, subgroup analyses and bias diagnostics

Table 4Go shows the pooled estimates for clinical failures of azithromycin versus the comparator antibiotics for each of the three conditions and subgroup analyses according to class of comparator. There was no evidence that azithromycin differed from the comparator agents for any of the three conditions. In a risk difference scale, the largest difference was only 0.5% and none of the 95% CIs extended beyond a difference of 2%. There were trends for superiority of azithromycin against penicillin and amoxicillin for acute otitis and sinusitis, but they did not reach formal significance. Trends in the opposite direction were seen for comparisons with other ß-lactams. Other macrolides were more effective than azithromycin in acute pharyngitis; but the significance of the finding is uncertain given the number of comparisons.


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Table 4. Summary estimates and 95% CIs for clinical failures with azithromycin versus comparators
 
There was no overt evidence of publication bias and inverted funnel plots were symmetrical for all three conditions. Similarly, there was no evidence that the treatment effect changed over time for more recent publications and for all three conditions the clinical failure rate in the comparator antibiotic arm was not significantly related to the treatment effect.

Adverse events

All 45 trials were considered in the safety analysis. Data on discontinuations due to adverse events were available in 33 trials. Data were not available in 12 trials for a total of 995 patients with upper respiratory tract infections receiving azithromycin. Overall, there were 37 discontinuations due to adverse events among 4870 patients receiving azithromycin (discontinuation rate of 0.8%). The specific reasons that led to discontinuation of azithromycin were not reported in 28 cases and in the other nine cases they were related to the gastrointestinal tract. The respective rates of discontinuation with other antibiotics were 0.6% for penicillin or amoxicillin, 1% for clarithromycin, 1.3% for cefaclor, 1.9% for erythromycin and 2.3% for co-amoxiclav (Table 5Go). There was a statistically significant higher discontinuation rate due to toxicity for co-amoxiclav than for azithromycin both in indirect and direct comparisons. Clarithromycin, erythromycin and cefaclor had a trend towards more discontinuations and amoxicillin or penicillin had a trend for fewer discontinuations, but neither was statistically significant even in indirect comparisons of all available data.


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Table 5. Discontinuation rates due to adverse events
 
Data on severe adverse events per study arm were available only in 20 trials. Fifteen of them observed no severe side effect from azithromycin and only five trials mentioned some severe side effects, precluding any meaningful conclusion.


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The meta-analysis indicates that for upper respiratory tract infections, azithromycin shows similar clinical failure rates to other antibiotics. These findings were consistent for acute otitis media, acute sinusitis and acute pharyngitis. All the 95% CIs exclude differences of more than 2% in clinical failures. Also, the available data indicate no superiority of azithromycin in terms of bacteriological response.

The overall results need to be interpreted with caution, as biases cannot be excluded. We found no evidence of overt publication bias, or changes in the pooled treatment effect over time. However, most trials were open-label and this could have affected the subjective determination of outcomes. Lack of allocation concealment may also cause bias in this setting. Moreover, it is difficult to interpret comparisons of azithromycin with specific antibiotic classes (macrolides, penicillins with or without ß-lactamase inhibitor and cephalosporins) because of the limited number of studies in each subgroup. Small trials are difficult to interpret in isolation. Although isolated RCTs of antibiotics are undertaken with the aim of showing equivalence rather than superiority, the sample size of individual RCTs of antibiotics is typically too small for equivalence testing,66 which requires over 1000 patients to exclude clinically meaningful differences in efficacy. Thus, meta-analysis provides an opportunity to establish or refute equivalence.67

The lack of demonstrable superiority of azithromycin or other antibiotics for these common conditions may relate to the fact that many of these infections resolve spontaneously. Randomized trials have challenged the use of antibiotics for acute otitis media.5–7 A meta-analysis has shown that one needs to treat 17 children with acute otitis media early with antibiotics to prevent one child from experiencing pain by 2–7 days after presentation.67 Similarly, clinical trials3,4 have found little evidence that antibiotics offer a clear benefit in uncomplicated acute sinusitis. A systematic literature review of acute sinusitis in children69 showed that the benefit of antibiotics is only modest and six children must be treated in order to achieve one additional cure. Two other recent meta-analyses2,70 showed that the benefit may be small and expensive, ‘broad-spectrum’ antibiotics seem to be as effective as amoxicillin and trimethoprim–sulfamethoxazole. The definition of acute bacterial sinusitis is problematic in the absence of culture from sinus puncture and aspiration. Spontaneous cure rates in placebo-controlled trials of acute otitis and sinusitis are high. Thus, it is unlikely that azithromycin would be superior to other antibiotics regardless of the relative microbial coverage.

The shorter treatment duration required for azithromycin may be important for patient compliance. However, some data indicate that comparator antibiotics may also be administered for shorter duration with efficacy similar to prolonged therapy. A randomized trial has shown that 3 days of trimethoprim–sulfamethoxazole is as effective as a 10 day regimen for acute uncomplicated sinusitis.8 Other trials have shown good efficacy for 1–5 day antibiotic regimens for acute otitis media.10–13,71,72 A recent systematic review9 of short-course antibiotics for acute otitis media showed that 44 children would need to be treated with a 10 day course of antibiotics to avoid one treatment failure due to treatment with a short course of antibiotics. Finally, despite the conventional wisdom that 10 days of antibiotic treatment are mandatory for streptococcal pharyngitis,73 recent trials have experimented with short-term courses for this common infection; success has not been consistent.14,74

Information on adverse events was not consistently reported in the trial reports, a deficiency we have previously observed in trials of antimicrobial chemotherapy.75,76 However, adequate information was reported on discontinuations due to adverse events. The available data indicate that azithromycin led to few discontinuations with only 37 of 4870 (0.76%) patients discontinuing therapy due to adverse events. The rate is comparable to our observations for azithromycin in lower respiratory tract infections.15 More detailed data on toxicity would be important to record in antibiotic trials, as tolerability is an important consideration. This is even more important for upper respiratory infections where the efficacy of antibiotics has been a controversial issue and their role has been questioned. The available evidence nevertheless indicates that azithromycin is safe in this setting. Tolerability is similar to that for penicillin or amoxicillin and better than that observed for co-amoxiclav. The estimates for discontinuation due to adverse events should be compared cautiously, as they are based on indirect comparisons, derived from different trial data.

If short-term treatment is sufficient, future trials may wish to consider testing ultra-short courses of azithromycin, such as the administration of a single 1.0–1.5 g dose. The pharmacokinetics of a single dose should allow adequate coverage for at least 3 days.77 One-dose azithromycin regimens have been used successfully in non-gonoccocal urethritis and cervicitis,78 but we did not identify any single-dose azithromycin trials for the treatment of common upper respiratory infections. Azithromycin is a relatively expensive antibiotic and a single-dose regimen may be more acceptable from the cost perspective as well.

Overall, azithromycin is safe and its shorter course is convenient, although the rationale for the longer courses used for its comparators is also questionable. There are no clinically meaningful differences in its efficacy for upper respiratory infections compared with other antibiotics. Cost, convenience and tolerability need to be considered for the choice of antibiotic treatment, but also for the decision on whether antibiotics should be used at all in upper respiratory infections.



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Figure 3. Meta-analysis of clinical failures of azithromycin versus comparator antibiotics for acute pharyngitis. Each study is shown by author name, number of patients, point estimate and 95% CI of odds ratio and comparator antibiotic used. Also shown are the pooled odds ratio and 95% CI by random effects calculations.

 

    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
This research was supported in part by an unrestricted grant from Pfizer Inc.


    Notes
 
* Corresponding author. Tel: +1-617-636-7670; Fax: +1-617-636-8023; E-mail: JLaul{at}lifespan.org Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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Received 25 January 2001; returned 19 July 2001; revised 6 August 2001; accepted 23 August 2001