Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections. A short (3-day) course of azithromycin tablets versus a 10-day course of amoxycillin-clavulanic acid (co-amoxiclav) in the treatment of adults with lower respiratory tract infections and effects on long-term outcome. Efficacy and tolerability of azithromycin versus amoxicillin/clavulanic acid in acute purulent exacerbation of chronic bronchitis. Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial. Simplified treatment of acute lower respiratory tract infection with azithromycin: a comparison with erythromycin and amoxycillin. European Azithromycin Study Group. Comparative study of azithromycin and amoxicillin/clavulanic acid in the treatment of lower respiratory tract infections. Comparison of azithromycin and co-amoxiclav in the treatment of acute tracheobronchitis and acute infectious exacerbations of chronic bronchitis in adults. Azithromycin Study Group. Once-daily, 3-day azithromycin versus a three-times-daily, 10-day course of co-amoxiclav in the treatment of adults with lower respiratory tract infections: results of a randomized, double-blind comparative study. A single-blind comparison of three-day azithromycin and ten-day co-amoxiclav treatment of acute lower respiratory tract infections. A randomized, comparative study to evaluate the efficacy and tolerability of a 3-day course of azithromycin versus a 10-day course of co-amoxiclav as treatment of adult patients with lower respiratory tract infections. Double-blind randomized study comparing the efficacies and safeties of a short (3-day) course of azithromycin and a 5-day course of amoxicillin in patients with acute exacerbations of chronic bronchitis. Azithromycin in upper respiratory tract infections: a clinical trial in children with otitis media. A multicenter, open label trial of azithromycin vs. amoxicillin/ clavulanate for the management of acute otitis media in children.
To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy. The efficacy and safety of a 3-day regimen of azithromycin prescribed in the new tablet form and of a 10-day regimen of amoxycillin clavulanic acid (co-amoxiclav, Augmentin) were compared in patients with acute lower respiratory tract infections. Of the 144 enrolled patients, 123 had a Type 1 acute exacerbation of chronic bronchitis (AECB), three patients had pneumonia, and 18 had purulent bronchitis. Treatment was successful, defined as cure or major improvement on day 14, in 59/62 (95%) patients in the azithromycin treatment group compared with 54/61 (90%) patients in the co-amoxiclav. At 30 days, the incidence of success was 77% (48/62) in the azithromycin treated group, compared with 66% (40/61) of co-amoxiclav-treated patients. At 60 days, incidences were 66% (41/62) and 59% (36/61), respectively. Several pathogens were isolated: Haemophilus influenzae in 21 patients (minimum inhibitory concentration (MIC) range for azithromycin 0.12-4 mg/l; co-amoxiclav 0.25-4 mg/l); Streptococcus pneumoniae in nine (MIC azithromycin < or = 0.06 > or = 256 mg/l; co-amoxiclav < or = 0.06-1 mg/l); and Moraxella catarrhalis in 11 (MIC azithromycin < or =0.06-2 mg/l; co-amoxiclav < or = 0.06-0.5 mg/l). Microbiological response rates were comparable. A significant correlation between clinical and microbiological cure was found (p = 0.02, power 0.6). In 15 (10%) patients, positive serology for viruses or atypical pathogens was found. In the co-amoxiclav-treatment group, 24 patients had mild adverse events (12 diarrhoea), compared with 27 treated with azithromycin (p = 0.47). It is concluded that a 3-day regimen of azithromycin prescribed as tablets is as clinically and microbiologically effective as a 10-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections. Moreover, since the percentage of viral infections was low and a significant correlation between microbiological and clinical cure was found, this study shows that clinical symptoms can be used to establish which patients with AECB (Type 1) should be treated with antimicrobial agents. An open randomized trial was conducted in 142 hospitalized and out-patients with acute purulent exacerbation of chronic bronchitis to compare the clinical efficacy and tolerability of azithromycin (n = 69) and amoxicillin/clavulanic acid (n = 73). Azithromycin (500 mg) was administered as a single dose for three days and amoxicillin/clavulanic acid (amoxicillin 875 mg-clavulanic acid 125 mg) was given b.i.d. for 8 days (8.16 +/- 1.18). Before therapy and 24-48 hours after the end of treatment, sputum culture (by positioning five orthodontal swabs at the opening of salivary gland ducts after a washing of the oral cavity with sterile saline solution to avoid oral contamination), chest X-rays, arterial blood gas analysis, trials of respiratory functions and routine blood tests were performed. In the azithromycin group (69 patients) the efficacy rate was 67.6% (46 patients: 34 cured and 12 improved); in 22 patients (32.4%) the treatment failed; 1 patient was not evaluated because of no follow-up. The overall efficacy rate in the amoxicillin/clavulanic acid group (73 patients) was 97.3% (71 patients: 60 cured and 11 improved); in 1 patient (1.4%) the treatment failed and 1 patient was a drop-out for side effects. All pathogens isolated before treatment were susceptible to the antibiotics administered. At the end of treatment microbiological efficacy was 67.1% in the azithromycin group and 98.6% in the amoxicillin/clavulanic acid group. The tolerability was judged good in both treatment groups. Side effects were observed in 1 patient treated with amoxicillin/clavulanic acid (diarrhea), which imposed interruption of treatment, and in 2 patients from the azithromycin group (gastralgia and biochemical laboratory tests: renal function).(ABSTRACT TRUNCATED AT 250 WORDS) The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial.
                Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat.
                The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler.
                Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder. In two randomized, multicentre studies azithromycin treatment (1.5 g in five or six doses over 5 days) was compared with erythromycin treatment (14 or 20 g in 28 or 40 doses over 7 or 10 days) and amoxycillin treatment (10.5 g in 21 doses over 7 days) in patients with acute respiratory tract infection. In the two separate studies, azithromycin gave complete clinical cure in 70% and 51%, respectively, of patients compared with in 60% of erythromycin- and 45% of amoxycillin-treated patients. Eradication of the main pathogens isolated at baseline (Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus) was comparable in the azithromycin, erythromycin and amoxycillin treatment groups. Efficacy was not affected by the presence or absence of underlying pulmonary disease. There were no major abnormalities in laboratory safety parameters and adverse events, principally mild/moderate gastro-intestinal symptoms occurred in 5% or 15%, respectively, of azithromycin-treated patients compared with in 18% or 17%, respectively, of those receiving erythromycin or amoxycillin. It is concluded that azithromycin was as effective and better tolerated than erythromycin or amoxycillin. Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 mg/day on days 2-5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillin/clavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92% and 87% of patients respectively, bacteriological cure in 89% and 86%, with 91% and 89% of pathogens eliminated. Minor side effects occurred in 6% and 12% of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group. Azithromycin, a broad-spectrum azalide, and co-amoxiclav were compared in a randomized, multicentre, open-label trial in 759 patients treated for acute tracheobronchitis (n = 620) or acute infectious exacerbations of chronic bronchitis (n = 139). Patients were randomized (2:1) to a 3-day regimen of two azithromycin 250 mg capsules once daily or a 5-10-day regimen of co-amoxiclav, one 625 mg tablet three times daily. Azithromycin produced a significantly higher cure rate (70.6% versus 61.1%) than co-amoxiclav (P = 0.011) and there were fewer failures (7.8% versus 13.6%) and relapses in the azithromycin-treated group, giving a higher overall response rate for azithromycin (89.7% versus 80.2%, P = 0.0003). With azithromycin, compliance was better than with co-amoxiclav and there was a significantly shorter time to improvement or cure. A higher incidence of adverse events, mostly gastrointestinal, was reported by patients taking co-amoxiclav (21.3% versus 14%, P = 0.0097), causing more patients in this group to discontinue therapy (7% versus 1.2%, P = 0.00004). A 3-day regimen of azithromycin (500 mg once daily) and a 10-day regimen of co-amoxiclav (625 mg three times daily) were compared in a double-blind study of 67 patients with acute infectious exacerbations of chronic bronchitis (AIECBs, n = 54), acute bronchitis (n = 7), or pneumonia (n = 6). In patients treated with azithromycin, satisfactory clinical responses (cure or improvement) were seen in 24/28 (86%) patients with AIECBs, 2/4 (50%) with acute bronchitis and 2/2 (100%) with pneumonia. Responses were satisfactory in 24/26 (92%), 4/4 (100%) and 4/4 (100%) patients, respectively, receiving co-amoxiclav. Streptococcus pneumoniae and Haemophilus influenzae were the commonest pathogens isolated at baseline. At the end of treatment, baseline pathogens were eradicated in 9/10 microbiologically-assessable patients treated with azithromycin and in 10/10 treated with co-amoxiclav. Adverse events related or possibly related to treatment occurred in five patients in each treatment group; the majority of these events affected the gastrointestinal system. One patient in each treatment group discontinued therapy because of adverse events. The study, therefore, demonstrates that 500 mg azithromycin administered once daily for 3 days is as efficacious and well tolerated as co-amoxiclav given three times daily for 10 days in the domiciliary treatment of adults with acute lower respiratory tract infections. The efficacy and safety of a three-day regimen of azithromycin (500 mg od) and a ten-day regimen of co-amoxiclav (625 mg tid) were compared in a single-blind study in 99 patients with acute lower respiratory tract infections. Of these, 70 (71%) suffered an infective exacerbation of their chronic obstructive pulmonary disease. Nine patients had pneumonia and 19 purulent bronchitis. Treatment success, defined as cure or improvement, occurred in 43 of 48 (90%) patients in the azithromycin group, compared with 45 of 51 (88%) patients in the co-amoxiclav group. The most common isolated pathogens were Haemophilus influenzae (25 cases; MIC range of azithromycin (A) < or = 0.06-4 mg/L; for co-amoxiclav (CA) 0.25-4 mg/L; Streptococcus pneumoniae (10 cases; A: < or = 0.06- > 128; CA: < or = 0.06); and Moraxella catarrhalis (four cases; A: < or = 0.06; CA: < or = 0.06-0.25). Microbiological response rates were comparable in the two groups. In 5% of patients, serological evidence for virus or atypical pathogens was found. Thirteen (26%) patients treated with co-amoxiclav had gastrointestinal complaints (seven with diarrhoea), compared with five (10%) treated with azithromycin (P = 0.09). Additional complaints occurred in three patients treated with co-amoxiclav and in one patient treated with azithromycin. It was concluded that a three-day regimen of azithromycin was as effective, clinically and microbiologically, as a ten-day regimen of co-amoxiclav in the treatment of acute lower respiratory tract infections. Clinical and bacteriological efficacy and tolerability of azithromycin (500 mg once daily for 3 days) and those of a 10-day regimen of co-amoxiclav (37 mg three times daily) were evaluated in a large-scale, double-blind comparative study of 369 patients (> or = 18 years old) with acute lower respiratory tract infections. After treatment, 165/173 (95%) azithromycin- and 166/173 (96%) co-amoxiclav-treated patients had responded satisfactorily (cure or improvement). Baseline pathogens (mainly Streptococcus pneumoniae and Haemophilus influenzae) were eradicated in 82/82 (100%) azithromycin- and 73/74 (99%) co-amoxiclav-treated patients who were bacteriologically assessable. Adverse events, which were predominantly of mild to moderate severity and mostly affected the gastrointestinal system, were recorded in 13/186 (7%) azithromycin- and 19/183 (10%) co-amoxiclav-treated patients. Only two (1%) azithromycin-treated patients discontinued treatment due to adverse events compared with eight (4%) who received co-amoxiclav. The results show that azithromycin at a dose of 500 mg once daily for 3 days is an effective and safe alternative to a 10-day, three-times-daily course of co-amoxiclav in the treatment of lower respiratory tract infections in adults. The efficacies and safeties of a three-dose regimen of azithromycin (500 mg once daily for 3 days) and a 15-dose regimen of amoxicillin (500 mg three times daily for 5 days) were compared in a double-blind manner in patients with an acute exacerbation of chronic bronchitis. A total of 92% of patients suffered a type 1 exacerbation. Treatment success, defined as cure or major improvement, was achieved in all patients in the azithromycin group by day 5, compared with 23 (92%) of 25 patients in the amoxicillin group. On day 12, these data were 24 of 25 (96%) in the azithromycin group and 20 of 25 (80%) in the amoxicillin group (results were not significantly different). Several pathogens were isolated (MIC ranges [micrograms per milliliter] in parentheses): Haemophilus influenzae or Haemophilus parainfluenzae was isolated 23 times (azithromycin, less than or equal to 0.06 to 32; amoxicillin, 0.12 to 2); Streptococcus pneumoniae was isolated from 11 patients (azithromcyin, less than or equal to 0.06 greater than 256; amoxicillin, less than or equal to 0.06 to 0.25); Moraxella (Branhamella) catarrhalis was isolated from eight patients (azithromycin, less than or equal to 0.06; amoxicillin, less than or equal to 0.06 to 16); and other members of the family Enterobacteriaceae were isolated from eight patients. One patient treated with azithromycin had Legionella pneumophila pneumonia, and another in that group had a significant rise in titer of antibody against influenza A virus. One patient treated with amoxicillin also had a significant rise in titer of antibody against influenza A virus. Microbiological response rates were comparable. One patient who received azithromycin developed abnormal liver function. Two patients treated with amoxicillin developed abnormal liver functions, one developed exanthema, and one treatment was stopped because of nausea. It is concluded that a three-dose (3-day) regimen of azithromycin is as effective clinically and microbiologically as a 15-dose (5-day) regimen of amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Azithromycin is a newly developed azalide antibiotic which is very active against microbes causing respiratory tract infections; tissue concentrations remain elevated for a long time after discontinuation of treatment. A clinical study was conducted to compare azithromycin (10 mg/kg administered as a single daily dose for 3 days) with amoxycillin/clavulanic acid (50 mg/kg/day given b.i.d. for 10 days) in 30 children with otitis media. Sensitivity testing demonstrated good azithromycin activity against beta-haemolytic streptococci, Moraxella catarrhalis, Haemophilus influenzae and Staphylococcus aureus. By day 12, clinical cure was recorded in 14/15 children treated with azithromycin and this was maintained at day 30. In the day 12 and 13/15 children by day 30. It was concluded that a 3-day azithromycin regimen produces a satisfactory clinical response and the eradication of key pathogens, and was acceptable for children. This randomized, open label study compared the efficacy and safety of a 5-day course of once daily azithromycin to those of a 10-day course of three times daily amoxicillin/ clavulanate.
                One hundred sixty-nine children with confirmed acute bacterial otitis media were randomized to treatment with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days or 40 mg/kg/ day of amoxicillin/clavulanate suspension in three divided doses for 10 days. Clinical efficacy and safety were evaluated on Days 11 and 30.
                Analysis of evaluable patients 11 days after the start of treatment demonstrated that 87.8% of patients treated with azithromycin and 100.0% of the patients treated with amoxicillin/ clavulanate were cured or improved. Presumed bacteriologic eradication of the baseline pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes was comparable in the two groups: 87.8% in patients treated with azithromycin; and 100.0% in patients receiving amoxicillin/clavulanate. At Day 30, 82.2% of patients treated with azithromycin and 80.0% of patients treated with amoxicillin/clavulanate were cured or improved. Presumed bacteriologic eradication of the base-line pathogens was similar in the two groups: 82.2% in patients treated with azithromycin; and 81.1% in patients receiving amoxicillin/clavulanate. Relapses occurred in 5.1% of patients receiving azithromycin and 21.1% of patients taking amoxicillin/clavulanate (P = 0.047). Treatment-related side effects occurred in 3.5% of the azithromycin patients compared with 31.0% of amoxicillin/clavulanate patients (P < 0.001).
                Azithromycin was comparable to amoxicillin/clavulanate in achieving clinical cure or improvement and presumed eradication of baseline pathogens in pediatric patients with acute otitis media. Azithromycin was significantly better tolerated and was associated with fewer relapses than seen after amoxicillin/clavulanate therapy.
There is unclear evidence that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxycillin or amoxyclav. However, most studies were of unclear methodological quality and small sample sizes; future trials of high methodological quality and adequate sizes are needed.