zithromax and Otitis-Media

Acute otitis media (AOM) is the inflammation of the middle ear. It constitutes one of the most frequent infections which affects children and usually occurs between 6 to 24 months of age. AOM can emerge due to viruses and/or bacteria. The aim of the current systematic review is to assess in children between 6 months and 12 years of age with AOM, the efficacy of any antimicrobial agent or placebo compared with amoxicillinclavulanate, to measure the resolution of AOM or symptoms.. The medical databases PubMed (MEDLINE) and Web of Science were used. Data extraction and analysis were performed by two independent reviewers. Eligibility criteria were set, and only randomised control trials (RCTs) were included. Critical appraisal of the eligible studies was performed. Pooled analysis was conducted using the Review Manager v. 5.4.1 software (RevMan).. Twelve RCTs were totally included. Three (25.0%) RCTs studied the impact of azithromycin, two (16.7%) investigated the impact of cefdinir, two (16.7%) investigated placebo, three (25.0%) studied quinolones, one (8.3%) investigated cefaclor and one (8.3%) studied penicillin V, compared to amoxicillin-clavulanate. In five (41.7%) RCTs, amoxicillin-clavulanate proved to be superior to azithromycin, cefdinir, placebo, cefaclor and penicillin V, while in seven (58.3%) RCTs its efficacy was comparable with other antimicrobials or placebo. The rates of AOM relapse after treatment with amoxicillin-clavulanate were comparable to those of other antimicrobials or placebo. However, amoxicillin-clavulanate was more effective in eradicating Streptococcus pneumoniae from the culture, when compared to cefdinir. The results of the meta-analysis were not evaluated due to substantial heterogeneity between studies.. Amoxicillin-clavulanate should be the treatment of choice for children between 6 months and 12 years of age with AOM.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cefaclor; Cefdinir; Child; Humans; Infant; Otitis Media; Penicillin V; Treatment Outcome

Resistance, prolonged therapy, and more adverse reactions made amoxicillin less preferred for treating otitis media. This study aimed to compare the efficacy and safety of azithromycin and amoxicillin/clavulanate for the treatment of otitis media in children.. This study was a systematic review and meta-analysis. PubMed, Cochrane library, and Google scholar databases were searched. Comparative randomized clinical trial studies between azithromycin and amoxicillin/clavulanate to treat otitis media in children published up to 30 September 2019 were included. The risk of bias was assessed and Data was extracted by the first author and checked by the second author. Meta-analysis was performed by STATA software version 16, and Mantel-Haenszel statistical method with effect measure odds ratio was employed for analysis.. 751 records were identified and 14 studies were eligible for analysis. In 12 studies azithromycin had equivalent clinical efficacy and 2 had less to amoxicillin/clavulanate. Meta-analysis results showed no statistically significant difference in efficacy in favor of amoxicillin/clavulanate after completion of treatment OR 0.75, 95% CI (0.62-0.91). On subgroup analysis for children less than 2 years (OR 0.96 95% CI (0.49-2.29), and greater than 2 years (OR 1.40 95% CI (0.93-2.11) and also efficacy on follow up (OR 0.97 95% CI (0.83-1.15) there is no statistically significant difference. The clinical adverse events are more in the amoxicillin/clavulanate group than in the azithromycin with a statistical significant difference OR 0.46 95% CI (0.43-0.56).. Azithromycin is comparable to amoxicillin/clavulanate to treat otitis media in children, and it is safer and more tolerable.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Biomarkers, Pharmacological; Child; Child, Preschool; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Infant; Male; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Failure

To determine the efficacy of a short course of antibiotics (<4 days) in comparison to a longer course (>4 days) for the treatment of acute otitis media in children.. Electronic databases, hand search of reviews, bibliographies of books, abstracts and proceedings of international conferences.. Randomized controlled trials of the empiric treatment of acute otitis media comparing antibiotic regimens of <4 days versus > 4 days in children between four weeks to eighteen years of age were included. The trials were grouped by pharmacokinetic behavior of short-course antibiotics into short-acting antibiotics, parenteral ceftriaxone, and long-acting azithromycin.. We reviewed 35 trials, which provided 38 analytic components. Overall, there was no evidence of an increased risk of treatment failure until one month with a short-course of antibiotics (RR=1.06, 95% CI 0.95 to 1.17, P=0.298). Use of short-acting oral antibiotic in short-course was associated with a significantly increased risk of treatment failure (RR=2.27, 95% CI: 1.04 to 4.99). There was a slightly increased risk of treatment failure with parenteral ceftriaxone (RR=1.13, 95% CI 0.99 to 1.30). The risk of adverse effects was significantly lower with short-course regimens (RR=0.58, 95% CI: 0.48 to 0.70).. There is no evidence of an increased risk of treatment failure with short course of antibiotics for acute otitis media. Among the short course regimens, azithromycin use was associated with a lower risk of treatment failure while short acting oral antibiotics and parenteral ceftriaxone may be associated with a higher risk of treatment failure.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Acute otitis media (AOM) is a common illness during childhood, for which antibiotics are frequently prescribed.. To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a long course of antibiotics (seven days or greater) for the treatment of AOM in children.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 4) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL, BIOSIS Previews, OCLC Papers First and Proceedings First, Proquest Dissertations and Theses (inception to November 2009); International Pharmaceutical Abstracts, the NLM Gateway, ClinicalTrials.gov and Current Controlled Trials (inception to August 2008).. Trials were included if they met the following criteria: participants aged one month to 18 years; clinical diagnosis of ear infection; no previous antimicrobial therapy; and randomisation to treatment with less than seven days versus seven days or more of antibiotics.. The primary outcome of treatment failure was defined as the absence of clinical resolution, relapse or recurrence of AOM during one month following initiation of therapy. Treatment outcomes were extracted from individual studies and combined in the form of a summary odds ratio (OR). A summary OR of 1.0 indicates that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of treatment.. This update included 49 trials containing 12,045 participants. Risk of treatment failure was higher with short courses of antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of therapy (21% failure with short-course treatment and 18% with long-course; absolute difference of 3% between groups). There were no differences found when examining treatment with ceftriaxone for less than seven days (30% failure in those receiving ceftriaxone and 27% in short-acting antibiotics administered for seven days or more) or azithromycin for less than seven days (18% failure in both those receiving azithromycin and short-acting antibiotics administered for seven days or more) with respect to risk of treatment failure at one month or less. Significant reductions in gastrointestinal adverse events were observed for treatment with short-acting antibiotics and azithromycin.. Clinicians need to evaluate whether the minimal short-term benefit from longer treatment of antibiotics is worth exposing children to a longer course of antibiotics.

Topics: Acute Disease; Age Factors; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Time Factors

Azithromycin is an azalide with in vitro activity against otitis media pathogens, good middle ear penetration and a prolonged half-life. A total of four clinical trials have evaluated the clinical success rate, safety and compliance of single-dose azithromycin (30 mg/kg) in the treatment of children with otitis media. Among all the patients treated with single-dose azithromycin (30 mg/kg), and presented previously in four published clinical trials, end-of-treatment clinical success was 88% (544 out of 619) and maintained clinical success at the end-of-study was 82% (498 out of 610). Three of the four studies included a mandatory baseline tympanocentesis. The overall end-of-treatment and end-of-study clinical success rates among all culture-positive patients was 84% (222 out of 263) and 80% (210 out of 263), respectively. Per pathogen end-of-treatment clinical success rates observed were 91% (125 out of 137) among patients with Streptococcus pneumoniae, 77% (75 out of 97) among patients with Haemophilus influenzae, 100% (14 out of 14) among patients with Moraxella catarrhalis, 64% (seven out of 11) among patients with baseline Streptococcus pyogenes and 25% (one out of four) among patients with a S. pneumoniae and H. influenzae mixed infection. Clinical success was observed in 90% (106 out of 118) of patients with baseline macrolide-susceptible S. pneumoniae and in 67% (14 out of 21) among patients with baseline macrolide-resistant S. pneumoniae (p = 0.01). Adverse events were uncommon, mostly mild and transitory gastrointestinal complaints, and in the two larger comparative trials, were less frequent than the rates observed with the comparator agents. Compliance was excellent (99-100%). Single-dose azithromycin (30 mg/kg) represents an alternative for the treatment of pediatric patients with uncomplicated acute otitis media, particularly in those geographic regions where high-level S. pneumoniae macrolide resistance is uncommon, and for those patients that require directly observed therapy or when compliance may be a problem.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Child; Drug Administration Schedule; Humans; Otitis Media

Expert panels have recommended high-dose amoxicillin (80-90 mg/kg/day) as the therapy of choice for uncomplicated acute otitis media in children. This recommendation is based primarily on pharmacokinetic data predicting bacteriologic cure of most middle ear infections by using amoxicillin at the recommended dosage. However, comparisons of aminopenicillin-containing regimens with alternative treatments, particularly azithromycin, have not consistently demonstrated superiority of the former, even in recent trials with stringent designs. Moreover, amoxicillin exposure may perturb nasopharyngeal colonization more profoundly than do alternative agents. These perturbations may theoretically promote the dissemination of beta-lactam-resistant pneumococci in the community more than other drugs approved for use in otitis media. Such findings suggest that several factors should be considered when choosing an agent to treat otitis media and that reexamination of high-dose amoxicillin as the superior first-line agent for this condition might be warranted.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; beta-Lactams; Child; Clinical Trials as Topic; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Otitis Media

Recurrent and persistent acute otitis media (AOM) is a common problem, affecting close to 20% of children in their first years of life. It presents a therapeutic challenge to physicians, particularly as beta-lactamase-producing Haemophilus influenzae, as well as penicillin- and, more recently, macrolide-resistant Streptococcus pneumoniae are often responsible for AOM in these patients. Intramuscular ceftriaxone (50 mg/kg, once daily for 3 days) has been shown to be effective in treating nonresponsive AOM, but there have been relatively few clinical trials exploring oral antibiotic regimens. Higher doses of commonly used antibiotics (amoxicillin-clavulanate ratio, 14:1 ratio and azithromycin 60 mg/kg divided into three equal once daily doses) have demonstrated high rates of clinical success. These studies will be discussed together with a review of the clinical and microbiologic characteristics of this disease. We will also address the impact that the pneumococcal conjugate vaccine may have on the microbiology of recurrent and persistent AOM.

Topics: Acute Disease; Azithromycin; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Prognosis; Randomized Controlled Trials as Topic; Recurrence; Severity of Illness Index; Streptococcus pneumoniae; Treatment Outcome

Oral azithromycin suspension has been prescribed to >80 million patients. Children find the color and taste of the oral suspension of azithromycin agreeable, and the drug is well-tolerated. On average 9% of patients have treatment-related adverse events, which are most frequently gastrointestinal complaints. The side effects are mild to moderate and very seldom necessitate withdrawal of the treatment. In addition to the conventional 3-day 10-mg/kg/day regimen and the 10 mg/kg on Day 1 followed by 5 mg/kg on Days 2 to 5 regimens, single dose 30 mg/kg and 3-day 20-mg/kg/day regimens are well-tolerated, although these new dosages are associated with more adverse effects.

Topics: Administration, Oral; Adolescent; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Male; Maximum Tolerated Dose; Otitis Media; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome

Topics: Acute Disease; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Pharyngitis; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Severity of Illness Index; Treatment Outcome

To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults.. A MEDLINE search (1990-September 2003) was performed to identify all pertinent studies and review articles. When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences.. All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections.. Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens. This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence. Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children. Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM. Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time.. Available data regarding single-dose azithromycin are promising. Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Community-Acquired Infections; Humans; Otitis Media; Pneumonia; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Safety

Acute otitis media (AOM) is the most frequent bacterial disease and leading cause of antibacterial prescriptions in infants and children. Although AOM resolves spontaneously in most patients, antibacterial treatment is believed to be indicated in most industrial countries, particularly for infants, to prevent severe complications and relieve symptoms more rapidly. The classical duration of oral antibacterial therapy has been 10 days. During the last decade, the efficacy of shortened course antibacterial therapy has been demonstrated in many trials. Advantages of shorter treatment periods include less expense, better compliance, and potentially less impact on the commensal flora. However, short course antibacterial therapy may not be appropriate for children <2 years of age, particularly those attending daycare centers, those with otorrhea or a recent episode (<1 month), and otitis-prone children. Reasons for a poorer efficacy in these groups of children are still not completely understood.

Topics: Acute Disease; Administration, Oral; Anti-Infective Agents; Azithromycin; Ceftriaxone; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Drug Resistance, Bacterial; Humans; Otitis Media; Russia

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.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Chi-Square Distribution; Confidence Intervals; Humans; Odds Ratio; Otitis Media; Pharyngitis; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sinusitis

Otitis media is a common pediatric problem, for which antibiotics are frequently prescribed.. To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a longer course (seven days or greater) for the treatment of acute otitis media in children.. The medical literature was searched for randomized controlled studies of the treatment of ear infections in children with antibiotics published from January 1966 to July 1997. Search last updated March 1998.. Studies were included if they met the following criteria: subjects one month to 18 years of age, clinical diagnosis of ear infection, no previous antimicrobial therapy and randomization to treatment with less than seven days versus seven days or more of antibiotics.. Data on treatment outcomes were extracted from individual studies, and combined in the form of a summary odds ratio. A summary odds ratio (OR) equivalent to one indicated that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of antibiotic.. The summary OR for treatment outcomes at eight to 19 days in 1,524 children treated with short-acting antibiotics for five days versus eight to 10 days was 1.52, 95% CI: 1.17-1.98, but by 20 to 30 days outcomes between treatment groups (n=2,115) were comparable (OR=1.22, 95% CI:0.98-1.54). The absolute difference in treatment failure (Random effects model RD=2.9%, 95%CI:-0.3% to 6.1%) at 20 to 30 days suggests that at minimum 17 children would need to be treated with the long course of short-acting antibiotics to avoid one treatment failure. Similarity in outcomes was observed for up to three months following therapy (OR=1.16,95% CI=0.9-1.5). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and more than seven days of other antibiotics.. This review suggests that five days of short-acting antibiotic is effective treatment for uncomplicated ear infections in children.

Topics: Acute Disease; Age Factors; Anti-Bacterial Agents; Azithromycin; Child; Drug Administration Schedule; Humans; Otitis Media

To conduct a meta-analysis of randomized controlled trials of antibiotic treatment of acute otitis media in children to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more.. MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations.. Studies were included if they met the following criteria: subjects aged 4 weeks to 18 years, clinical diagnosis of acute otitis media, no antimicrobial therapy at time of diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7 days or more of antibiotic treatment.. Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections.. Included trials were grouped by antibiotic used in the short course: (1) 15 short-acting oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate], cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil), (2) 4 intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The summary odds ratio for treatment outcomes at 8 to 19 days in children treated with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups were comparable (odds ratio, 1.22; 95% CI, 0.98 to 1.54). The risk difference (2.3%; 95% CI,-0.2% to 4.9%) at 20 to 30 days suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. This similarity in later outcomes was observed for up to 3 months following therapy (odds ratio, 1.16; 95% CI, 0.90-1.50). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and at least 7 days of other antibiotics.. This meta-analysis suggests that 5 days of short-acting antibiotic use is effective treatment for uncomplicated acute otitis media in children.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Cephalosporins; Child; Drug Administration Schedule; Humans; Otitis Media; Randomized Controlled Trials as Topic; Treatment Outcome

Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild. Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Drug Tolerance; Humans; Infant; Otitis Media; Pharyngitis; Respiratory Tract Infections; Streptococcal Infections; Tonsillitis

Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most frequently isolated pathogens in patients with acute otitis media (AOM). Other potential causative pathogens include Streptococcus pyogenes in older children and Chlamydia pneumoniae in younger children. The recent emergence of penicillin-resistant S. pneumoniae and the increasing frequency of beta-lactamase-producing strains of M. catarrhalis and H. influenzae are creating concerns regarding the use of amoxicillin as traditional first line empiric therapy for AOM in younger children. Both the in vitro antibiotic activity against these more resistant causative pathogens and the antibiotic concentrations achieved in middle ear fluid must be considered when selecting antibiotics for treatment of refractory AOM. The newer macrolides, azithromycin and clarithromycin, provide reasonable in vitro coverage against penicillin-resistant S. pneumoniae and beta-lactamase-producing H. influenzae, although azithromycin is more active against the latter. Both drugs also achieve notably higher, sustained concentrations in middle ear fluid than do beta-lactam antibiotics. Thus the newer macrolides represent important new rational alternatives for the management of AOM.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactam Resistance; Child; Child, Preschool; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Moraxella catarrhalis; Neisseriaceae Infections; Otitis Media; Penicillin Resistance; Penicillins; Streptococcal Infections; Streptococcus pneumoniae

A randomized, double-blind, double-dummy, multicenter international study was conducted to assess the clinical and bacteriologic response, safety, and compliance of a single 60-mg/kg dose of azithromycin extended-release (ER) versus a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in children with acute otitis media at high risk of persistent or recurrent middle ear infection.. Children aged 3 to 48 months were enrolled and stratified into two age groups (≤ 24 months and >24 months). Pretreatment tympanocentesis was performed at all sites and was repeated during treatment at selected sites.. The primary endpoint, clinical response at the test-of-cure visit in the bacteriologic eligible population, was achieved in 80.5% of children in the azithromycin ER group and 84.5% of children in the amoxicillin/clavulanate group (difference-3.9%; 95% confidence interval-10.4, 2.6). Bacteriologic eradication was 82.6% in the azithromycin ER group and 92% in the amoxicillin/clavulanate group (p=0.050). Children who received amoxicillin/clavulanate had significantly higher rates of dermatitis and diarrhea, a greater burden of adverse events, and a lower rate of compliance to study drug compared to those who received azithromycin ER.. A single 60-mg/kg dose of azithromycin ER provides near equivalent effectiveness to a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in the treatment of children with acute otitis media.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Humans; Infant; Otitis Media; Treatment Outcome

An azithromycin extended-release (ER) oral suspension was developed to improve the gastrointestinal tolerability profile without substantially compromising systemic exposure. A single dose of 30 mg/kg azithromycin immediate-release (IR) oral suspension has been used in children to treat acute otitis media (AOM). This study was conducted to compare the pharmacokinetics of a 60-mg/kg azithromycin ER single dose with a 30-mg/kg azithromycin IR single dose in children with AOM aged 6 months to 6 years (n = 19 per treatment). Serum samples were collected at 1, 2, 3, 4, 8, 24, 48, and 72 h after dosing. The area under the curve from time zero to 72 h postdosing (AUC(0-72)) was calculated based on a noncompartmental method. One-way analysis of variance (ANOVA) was used to compare exposure parameters (e.g., AUC(0-72) and peak concentration) as well as concentrations at each time point. The adjusted geometric mean ratio of the ER/IR AUC(0-72) was 157.98% (90% confidence interval [CI], 98.87%, 252.44%), which met the predefined criterion of the lower boundary of the 90% CI of ≥ 80%. As expected, due to the slower-release profile of the ER formulation, the concentrations of the ER formulation during the first 3 h were lower than those of the IR formulation. After 3 h postdosing, the lower boundaries of the 90% CI for the ER/IR concentration ratios were greater than 100%. These results indicated that a 60-mg/kg single dose of ER azithromycin provides similar or greater systemic exposure in children than the 30-mg/kg single dose of IR azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Chemistry, Pharmaceutical; Child; Child, Preschool; Humans; Infant; Otitis Media

To compare the clinical effectiveness of single-dose azithromycin treatment with 7 days of amoxycillin treatment among Aboriginal children with acute otitis media (AOM) in rural and remote communities in the Northern Territory.. Aboriginal children aged 6 months to 6 years living in 16 rural and remote communities were screened for AOM. Those diagnosed with AOM were randomly allocated to receive either azithromycin (30 mg/kg as a single dose) or amoxycillin (50mg/kg/day in two divided doses for a minimum of 7 days). We used a double-dummy method to ensure blinding. Our study was conducted from 24 March 2003 to 20 July 2005.. Failure to cure AOM by the end of therapy; nasal carriage of Streptococcus pneumoniae and non-capsular Haemophilus influenzae (NCHi).. We followed 306 of 320 children (96%) allocated to the treatment groups. Single-dose azithromycin did not reduce (or increase) the risk of clinical failure (50% failure rate [82/165]) compared with amoxycillin (54% failure rate [83/155]) (risk difference [RD], - 4% [95% CI, - 15% to 7%]; P = 0.504). Compared with amoxycillin, azithromycin significantly reduced the proportion of children with nasal carriage of S. pneumoniae (27% v 63%; RD, - 36% [95% CI, - 47% to - 26%]; P < 0.001) and NCHi (55% v 85%; RD, - 30% [95% CI, - 40% to - 21%]; P < 0.001). Nasal carriage of S. pneumoniae with intermediate or full resistance to penicillin was lower (but not significantly so) in the azithromycin group (10% v 16%), but this group had significantly increased carriage of azithromycin-resistant S. pneumoniae (10% v 3%; RD, 7% [95% CI, 0.1% to 12%]; P = 0.001). Carriage of beta-lactamase-producing NCHi was about 5% in both groups.. Although azithromycin reduced nasal carriage of S. pneumoniae and NCHi, clinical failure was high in both treatment groups. The possibility of weekly azithromycin treatment in children with persistent AOM should be evaluated.. Australian Clinical Trials Registry ACTRN 12609000691246.

Topics: Amoxicillin; Anti-Bacterial Agents; Australia; Azithromycin; Child; Child, Preschool; Confidence Intervals; Double-Blind Method; Female; Haemophilus influenzae; Humans; Infant; Male; Native Hawaiian or Other Pacific Islander; Nose; Odds Ratio; Otitis Media; Streptococcus pneumoniae; Tympanic Membrane Perforation

The use of short-term intramuscular ceftriaxone for pediatric ambulatory conditions raises concerns regarding the promotion of resistance among colonizing enteric bacteria. This study was designed to assess the prevalence of stool colonization with resistant Gram-negative bacilli after single-dose ceftriaxone treatment compared with other regimens for acute otitis media.. Children age 3 months to 7 years and diagnosed with acute otitis media were randomized to receive treatment with single-dose ceftriaxone or with oral cefprozil, amoxicillin or azithromycin. Stool samples were obtained at enrollment and then 3-5 days, 10-14 days, and 28-30 days after therapy was initiated and screened for the presence of facultative Gram-negative bacilli resistant to ceftriaxone, cefprozil, amoxicillin, piperacillin, piperacillin-tazobactam and tobramycin. Mean prevalence of colonization by resistant organisms for each treatment group was compared at each time point.. One thousand nine subjects were enrolled. The prevalence of colonization by a Gram-negative bacillus resistant to at least 1 of the screening antibiotics decreased after receipt of ceftriaxone but returned close to values measured at study entry by 30 days. A qualitatively similar pattern was noted for the 3 other regimens, but a quantitatively greater decrease in the prevalence of colonization by a resistant bacterium was noted at the 3- to 5-day and 10- to 14-day visits among azithromycin recipients (P < 0.001). Colonization by a Gram-negative bacillus resistant specifically to ceftriaxone was unusual at each study visit, regardless of treatment assignment.. A single intramuscular dose of ceftriaxone had a similar effect on the prevalence of antibiotic-resistant Gram-negative facultative bacilli in the stool of healthy children when compared with commonly used oral agents.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefprozil; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance; Feces; Female; Gram-Negative Bacteria; Humans; Infant; Injections, Intramuscular; Male; Otitis Media

Acute otitis media (AOM) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy. Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported.. To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate.. This prospective, single blind, randomised comparative study was carried out in 180 children with AOM. Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy. Children with acute otitis media were randomised to receive either low dose amoxicillin-clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or low dose azithromycin (10mg/kg/day for 3 days). Clinical response was assessed on days 2-4, 11-13, 26-28.. Bacterial pathogens were isolated from 108 (60%) of 180 children. Streptococcus pneumoniae was the most common isolated pathogen (39.7%), followed by Haemophilus influenzae (20.7%), Moraxella catarrhalis (15.5%), Staphylococcus aureus (13.8%), Group A beta-hemolytic streptococcus (5.1%), Escherichia coli (3.4%) and Enterococcus faecalis (1.7%). This study demonstrated low resistance rates compared to studies of different countries. Although clinical response rates were better in patients treated with amoxicillin-clavulanate, this was not statistically significant [86.6% (78 of 90)] versus [95.2% (80 of 84)]. Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae. Difference between success rates was not statistically significant (P=0.144 and 0.352).. Bacteria were isolated in 60% of AOM cases. The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Otitis Media; Prospective Studies; Single-Blind Method; Treatment Outcome

High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM.. To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM.. This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study).. The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001).. In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Moraxellaceae Infections; Otitis Media; Patient Compliance; Pneumococcal Infections; Streptococcal Infections; Streptococcus pyogenes

A large dosage pediatric formulation of amoxicillin/clavulanate with an improved pharmacokinetic/pharmacodynamic profile was developed to eradicate many penicillin-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae (including beta-lactamase-producing strains).. This randomized, investigator-blinded, multicenter trial examined treatment of bacterial acute otitis media (AOM) in children 6-30 months of age with amoxicillin/clavulanate (90/6.4 mg/kg/d in 2 divided doses for 10 days) versus azithromycin (10 mg/kg for 1 day followed by 5 mg/kg/d for 4 days). Tympanocentesis was performed at entry for bacteriologic assessment, at the on-therapy visit (day 4-6) to determine bacterial eradication and at any time before the end-of-therapy visit (day 12-14) if the child was categorized as experiencing clinical failure. Clinical assessments were performed at the on-therapy, end-of-therapy and follow-up (day 21-25) visits.. We enrolled 730 children; AOM pathogens were isolated at baseline for 249 of the amoxicillin/clavulanate group and 245 of the azithromycin group. For children with AOM pathogens at baseline, clinical success rates at the end-of-therapy visit were 90.5% for amoxicillin/clavulanate versus 80.9% for azithromycin (P < 0.01), and those at the on-therapy and follow-up visits were 94.9% versus 88.0% and 80.3% versus 71.1%, respectively (all P < 0.05). At the on-therapy visit, pretherapy pathogens were eradicated for 94.2% of children receiving amoxicillin/clavulanate versus 70.3% of those receiving azithromycin (P < 0.001). Amoxicillin/clavulanate eradicated 96.0% of S. pneumoniae (92.0% of fully penicillin-resistant S. pneumoniae) and 89.7% of H. influenzae (85.7% [6 of 7 cases] of beta-lactamase-positive H. influenzae). Corresponding rates for azithromycin were 80.4% (54.5%) for S. pneumoniae and 49.1% (100% [1 of 1 case]) for H. influenzae (all P < 0.01 for between-drug comparisons).. Amoxicillin/clavulanate was clinically and bacteriologically more effective than azithromycin among children with bacterial AOM, including cases caused by penicillin-resistant S. pneumoniae and beta-lactamase-positive H. influenzae.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Female; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Streptococcus pneumoniae; Treatment Outcome

Short-course therapy for acute otitis media (AOM) improves adherence and may reduce secondary bacterial resistance.. In this multicenter, prospective, investigator-blinded study, patients between the ages of 6 months and 6 years with a clinical diagnosis of AOM were randomized to receive cefdinir oral suspension 7 mg/kg q12h for 5 days or azithromycin oral suspension 10 mg/kg once daily on day 1 and 5 mg/kg once daily on days 2 through 5. Clinical response was assessed at the end-of-therapy (EOT) visit (days 7-9) and the follow-up visit (days 20-25).. Three hundred fifty-seven patients were enrolled in the study. The treatment groups were similar at baseline with respect to demographic characteristics (mean [SD] age, 3.0 [1.7] years; 55% male), incidence of bilateral AOM (45%), and presenting signs and symptoms. The majority of evaluable children (77%) had previously received conjugated heptavalent pneumococcal vaccine (PCV7) against Streptococcus pneumoniae. At the EOT visit, clinical cure rates were comparable for cefdinir and azithromycin (87% [151/174] and 85% [149/176], respectively; 95% CI, -5.5 to 9.8). In addition, clinical cure rates at the EOT visit in the children who had been vaccinated with PCV7 were comparable between cefdinir and azithromycin (86% vs 83%; 95% CI, -6.5 to 11.8). No significant difference in clinical cure rates was observed at the follow-up visit (76% and 86%; 95% CI, -18.9 to 0.0). Parental satisfaction was similar between treatment groups with regard to ease of use, taste, compliance, health care resource utilization, and missed days of work and day-care. Both antibiotics were well tolerated; diarrhea and abnormal stools were the most common antibiotic-related adverse events (< or = 7% each).. Short courses (5 days) of therapy with cefdinir or azithromycin were comparable in these children with AOM based on clinical end points, parental preferences, and health care utilization.

Topics: Acoustic Impedance Tests; Acute Disease; Administration, Oral; Analgesics; Analgesics, Non-Narcotic; Anti-Infective Agents; Anti-Inflammatory Agents; Azithromycin; Cefdinir; Cephalosporins; Child, Preschool; Diarrhea; Drug Administration Schedule; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Male; Meningococcal Vaccines; Otitis Media; Pneumococcal Vaccines; Prospective Studies; Single-Blind Method; Streptococcus pneumoniae; Time Factors; Treatment Outcome; Tympanic Membrane

Acute otitis media (AOM) is a common childhood infection that is frequently treated by antibiotics. There are no prospective and comprehensive trials evaluating childhood AOM for etiologic pathogens and resistance pattern in Turkey. The aims of the study were to determine the bacterial etiologies and resistance patterns, and identify the efficacy and the relapse rates of 3 days of azitromycin and 10 days of cefaclor therapy in AOM.. This prospective, randomized, single-blind, open study was carried out in 78 cases of AOM. Mean age was 30.7+/-27 months. Tympanocentesis and aspiration of middle ear fluid (MEF) were used to obtain purulent material from the middle ear. Group 1 consisted of the cases (n=41) on azitromycin therapy and Group 2 (n=37) on cefaclor. Dosage of azitromycin was 10 mg/kg per day for 3 days and cefaclor 40 mg/kg per day for 10 days. The patients were evaluated on days 3-5 (second visit), day 10 (third visit), and day 30 (fourth visit) during follow-up.. A total of 50 species were isolated from 44 of 78 cases from which materials were obtained (44/78; 56.4%). Most frequently isolated microorganism was Streptococcus pneumoniae (n=18; 36%), followed by Haemophilus influenzae (n=11; 22%), S. aureus (n=9; 18%), Moraxella catarrhalis (n=4; 8%), and group A beta-hemolytic streptococcus (GAS, n=4; 8%). Enterococcus faecalis was isolated from three cases and H. parainfluenzae from one. Penicillin and amoxicillin resistances of bacteria were found to be 40 and 36%, respectively. The frequency of penicillin and amoxicillin resistance in

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Cefaclor; Child; Child, Preschool; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Otitis Media; Prospective Studies; Single-Blind Method; Time Factors

Children with acute otitis media underwent tympanocentesis and were given a single dose of 30 mg of azithromycin/kg of body weight. At day 28, the overall clinical cure rate was 206 of 242 (85%). Clinical cure rates for patients infected with Streptococcus pneumoniae (67 of 76; 88%) and Haemophilus influenzae (28 of 44; 64%) were consistent with historical rates for the 5-day dosing regimen.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Combined Modality Therapy; Drainage; Female; Humans; Infant; Male; Otitis Media

Compared with 5 days of dosing, a 3 day dosing regimen of azithromycin for treatment of acute otitis media (AOM) may improve compliance, will simplify therapy for the caregiver and, by giving the same total dose as the 5 day regimen, provide more drug when the bacterial burden is highest.. Children of 6 months-12 years were enrolled if they had had symptoms and signs of AOM for <4 weeks and tympanic membrane effusion by acoustic reflectometry. Eligible children were randomized to azithromycin 10 mg/kg/day x 3 days or co-amoxiclav 45 mg/kg/day x 10 days. The primary endpoint was clinical response at day 28.. One hundred and eighty-eight children (mean age 3.5 years) were randomized to azithromycin and 185 to co-amoxiclav. At day 10, the clinical success rate was 153/185 (83%) in children treated with azithromycin and 159/181 (88%) in children treated with co-amoxiclav. At day 28, 134/182 (74%) of the children were cured on azithromycin compared with 124/180 (69%) on co-amoxiclav. Also at day 28, signs of AOM, such as abnormal reflectometry (45% versus 59%; P = 0.017), bulging of the eardrum (10% versus 16%; P = 0.059) and loss of tympanic membrane landmarks (11% versus 22%; P = 0.010) were seen less frequently in azithromycin- than co-amoxiclav-treated children, respectively. Adverse events related to therapy were seen in 11% of azithromycin patients compared with 20% on co-amoxiclav (P = 0.014).. Azithromycin given over 3 days is as effective as co-amoxiclav for treatment of AOM, may result in more complete resolution of tympanic membrane disease, and is better tolerated.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Hearing Tests; Humans; Infant; Male; Otitis Media; Treatment Outcome; Tympanic Membrane

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Patient Compliance; Penicillins; Recurrence; Treatment Outcome

Prior use of antibiotics is associated with carriage of resistant bacteria. Colonization by Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha-hemolytic streptococci (NPAHS), and Staphylococcus aureus was evaluated in children receiving antibiotic therapy for acute otitis media and in untreated, healthy control subjects. Children were randomly assigned to receive either amoxicillin/clavulanate (90 mg/kg per day) or azithromycin. Swabs were obtained before initiating therapy and again 2 weeks and 2 months after initiating therapy. We also obtained swabs from control subjects at the time of enrollment and 2 weeks and 2 months after enrollment. The decrease in the rate of carriage of S. pneumoniae and H. influenzae at 2 weeks was significant only in the amoxicillin/clavulanate group (P<.001 and P=.005, respectively). The rate of nasopharyngeal colonization with NPAHS among treated patients increased from 23% to 39% at 2 months (P=.01). This increase was similar for both treatment groups. These results suggest that the competitive balance between organisms is altered by antibiotic therapy.

Topics: Acute Disease; Amoxicillin; Azithromycin; Bacterial Infections; Child, Preschool; Clavulanic Acid; Drug Therapy, Combination; Female; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Male; Nasopharyngeal Diseases; Otitis Media; Serotyping; Staphylococcus aureus; Streptococcus; Streptococcus pneumoniae

Antibiotic-resistant pneumococci are difficult to eradicate from middle ear fluid (MEF) and the nasopharynx (NP). Bacteriologic eradication from the NP and MEF during acute otitis media (AOM) by 3 common antibiotic drugs was prospectively evaluated. In 19 (16%) of 119 MEF culture-positive patients, an organism susceptible to the treatment drug (Haemophilus influenzae, Streptococcus pneumoniae, or both) was isolated from the initial MEF, whereas resistant S. pneumoniae was present in the NP; in 9 (47%) patients, the initial resistant NP organism (identified by serotyping, resistance to the administered drug, and pulsed-field gel electrophoresis) replaced the susceptible MEF organism within only a few days after initiation of treatment. In regions where resistant pneumococci are prevalent, antibiotics may not only fail to eradicate the organisms, but they may often induce MEF superinfection with resistant pneumococci initially carried in the NP. This is an important mechanism by which, in recently treated patients, AOM infections often become refractory to treatment.

Topics: Acute Disease; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Microbial; Drug Therapy, Combination; Ear, Middle; Female; Humans; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Superinfection; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the outcome of patients with recurrent acute otitis media (AOM) treated either with amoxicillin or with azithromycin.. This prospective, controlled, and randomized study, compares the outcome of 71 patients with recurrent AOM treated with azithromycin (31 patients) or amoxicillin (40 patients) for the prevention of AOM. azithromycin was given at a dose of 10 mg/kg once a week, whereas amoxicillin was administered daily as a single intake of one third of the therapeutic dosage (20 mg/kg per day). All treatments were prescribed for 3 months. Both groups were homogeneous with regard to the currently accepted predisposing factors of recurrent AOM. Mean age of children was 35.3 months, and average follow-up was 11.5 months. The treatment was considered effective when the number of episodes of AOM dropped to less than 50% after the prophylaxis.. Patients in the azithromycin group had a clinical response to prophylaxis (80.6%) comparable to those treated with amoxicillin (89.5%) (P=0.300). The incidence of adverse effects was similar in both groups.. According to these results, a prophylaxis with azithromycin is as useful as amoxicillin to prevent recurrent AOM.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Male; Otitis Media; Penicillins; Probability; Prospective Studies; Reference Values; Secondary Prevention; Treatment Outcome

A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Azithromycin; Cefaclor; Child, Preschool; Female; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Otitis Media; Prospective Studies; Streptococcus pneumoniae

The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media. Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy. Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S. pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin. Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S. pneumoniae but none of azithromycin-nonsusceptible strains. Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy. Carriage of H. influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate. Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains.

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Carrier State; Child; Child, Preschool; Clavulanic Acid; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Nasopharynx; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

We compared colonization and resistance rates of non-pneumococcal alpha-hemolytic streptococci (AHS) and Streptococcus pneumoniae in children receiving antibiotic therapy for acute otitis media.. Between December 1997 and September 1998, children 6 months to 6 years of age, diagnosed with acute otitis media were randomly assigned to receive amoxicillin/clavulanate (Augmentin) 45 mg/kg/d in 2 divided doses for 10 days or azithromycin (Zithromax), 10 mg/kg, once on the first day, followed by 5 mg/kg daily for 4 days. Nasopharyngeal swabs for culture were obtained before and at 2 weeks and 2 months after the start of therapy. Streptococci were identified by species, and antibiotic susceptibility was determined by the epsilometric test.. One hundred six children completed the 2-week follow-up and 2-month follow-up, respectively. The nasopharyngeal carriage rate of non-pneumococcal AHS increased from 14% before treatment to 32% at the 2-week follow-up (P =.02) and was similar in both treatment groups. In contrast, the carriage of S pneumoniae decreased from 51% before therapy to 27% at the 2-week follow-up (P =.002). The carriage of penicillin-resistant AHS strains (minimum inhibitory concentration > 1 microg/mL) increased from 9% before treatment to 26% at 2 weeks and 36% at 2 months.. Amoxicillin/clavulanate and azithromycin therapy resulted in increased isolation of nasopharyngeal non-pneumococcal AHS, many of which were multidrug-resistant, in contrast to a decrease in pneumococcal carriage. This suggests that the competitive balance between these 2 groups of organisms was disturbed as a result of differential antibiotic susceptibility. The importance of drug-resistant AHS as a reservoir for resistance genes for S pneumoniae warrants further investigation.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; beta-Lactam Resistance; Child, Preschool; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Infant; Male; Nasopharynx; Otitis Media; Streptococcus; Streptococcus pneumoniae

A comparison was made of the clinical effectiveness of azithromycin (once daily for three days at a dose of 10 mg/kg in children or 500 mg/day in adults) and amoxicillin/clavulanic acid and cefaclor (standard doses for 7 to 14 days) in acute ear, nose and throat infections in an open randomized study. The group with azithromycin included 37 otitis media, 24 pharyngotonsillitis and 6 maxillary sinusitis (n = 67). The amoxicillin/clavulanic acid group, 22 otitis media, 19 pharyngotonsillitis and 6 maxillary sinusitis (n = 47) and the cefaclor group, 15 otitis media, 12 pharyngotonsillitis and 4 maxillary sinusitis (n = 31). Fifteen days after beginning treatment, 97% (65/67) of the patients who received azithromycin had improved or cured, compared with 85% (40/47) of those who received amoxicillin/clavulanic acid and 84% (26/31), cefaclor (p < 0.02). Pathogens were not eradicated in 3% (2/58) of the patients who received azithromycin, compared with 13% (4/28) who received amoxicillin/clavulanic acid and 15% (4/28) cefaclor. Patients with azithromycin showed an earlier clinical improvement and more rapid normalization of the leukocyte count, erythrocyte sedimentation rate and acute phase proteins. No patient with azithromycin had adverse effects, versus 15% (7/47) for patients with amoxicillin/clavulanic acid and 16% (5/31) for cefaclor. Treatment compliance was 100, 83 (39/47) and 84% (26/31), respectively (p < 0.01). We conclude that azithromycin treatment for three days is faster and more effective clinically and analytically than standard treatment with amoxicillin/clavulanic acid or cefaclor in acute infections of the ear, nose and throat.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Azithromycin; Cefaclor; Cephalosporins; Clavulanic Acid; Female; Humans; Male; Maxillary Sinusitis; Otitis Media; Penicillins; Pharyngitis; Tonsillitis

An open, multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media. Patients were randomized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days. Cure or improvement in signs and symptoms was observed in 112/114 (98%) evaluable azithromycin-treated patients and 116/120 (97%) evaluable cefaclor-treated patients on days 11-15. In contrast to cefaclor, however, azithromycin was associated with a significantly (P = 0.033) higher cure rate 1 month after completion of treatment. In those patients who were followed up to days 25-30, the response was satisfactory (cure or improvement) in 31/32 (97%) patients who had received azithromycin and in 31/36 (86%) to whom cefaclor had been administered. Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group. The results of this study show that a 3-day, once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days, but the azithromycin is associated with a lower incidence of relapse.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Cefaclor; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Male; Otitis Media

In this multicenter, open label trial the investigators evaluated the efficacy and safety of azithromycin suspension administered once daily for 5 days for the treatment of clinically and bacteriologically established acute otitis media.. Two hundred eligible children with acute otitis media from 10 US centers were treated with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days. Tympanocentesis and subsequent culture of middle ear effusion were performed at baseline. Clinical efficacy was evaluated on Days 6, 11 and 30.. Analysis of clinical efficacy in evaluable patients 11 days after the initiation of therapy showed that the rate of satisfactory responses (cured or improved) ranged from 79.6 to 82.4% in patients infected with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Satisfactory clinical response at Day 30 was reported in 70% of evaluable patients, and eradication of S. pneumoniae, H. influenzae and M. catarrhalis was presumed in 64 to 73%. Relapses occurred in 14% of the evaluable patients. Among the treated patients 8.5% reported mild or moderate side effects.. Azithromycin is an effective, safe and well-tolerated treatment for children with acute otitis media.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Administration Schedule; Female; Haemophilus Infections; Humans; Male; Moraxella catarrhalis; Neisseriaceae Infections; Otitis Media; Pneumococcal Infections

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.

Topics: Acute Disease; Adolescent; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Otitis Media

To compare the efficacy and safety of azithromycin and amoxicillin/clavulanate in pediatric acute otitis media.. Investigators from 12 US centers recruited 677 children. In a randomized, double blind, double dummy fashion, participants received either azithromycin suspension (n = 341) once daily for 5 days or amoxicillin/clavulanate suspension (n = 336) in three divided doses daily for 10 days.. Among evaluable patients satisfactory clinical response rates (cured and improved) measured 11 days after therapy began were 87.5% in the azithromycin group and 87.9% in the amoxicillin/clavulanate group; corresponding rates at 30 days were 73.5% in the azithromycin and 71.2% in the amoxicillin/clavulanate groups. Relapse rates were comparable for the treatment groups. Treatment-related side effects, primarily gastrointestinal, were reported significantly less frequently with azithromycin (8.8%) than with amoxicillin/clavulanate (30.8%) (P < 0.0001). Two (0.6%) azithromycin patients and 12 (3.6%) amoxicillin/ clavulanate patients discontinued therapy because of treatment-related side effects (P < 0.006 between groups).. In these children with acute otitis media, azithromycin given once daily for 5 days and amoxicillin/clavulanate given three times daily for 10 days had similar efficacy; however, azithromycin was significantly better tolerated.

Topics: Acute Disease; Adolescent; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clavulanic Acids; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Infant; Otitis Media

This multicenter, randomized, open label study compared the efficacy and safety of azithromycin and amoxicillin/clavulanate for the treatment of acute otitis media among children who were attending a day-care facility or school.. Eligible children with acute otitis media from 21 US centers 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 approximately 40 mg/kg/day of amoxicillin/clavulanate suspension in 3 divided doses for 10 days. Clinical efficacy was evaluated on Days 14, 30 and 45. Acceptance and convenience of the medications were assessed on Day 14 by parent interviews with a standardized questionnaire.. Of the 263 children enrolled in the study, 233 were evaluable at the primary evaluation 45 days after the start of treatment. Satisfactory clinical response rates (cure, delayed cure and improvement) were 60.5% in patients treated with azithromycin and 64.9% in patients treated with amoxicillin/clavulanate. Satisfactory clinical response rates at secondary evaluations were also comparable: 92.2% vs. 90.0% at Day 14 and 66.7% vs. 72.7% at Day 30 in patients treated with azithromycin and amoxicillin/clavulanate, respectively. No significant differences in treatment failures, relapses or recurrences were noted with either medication. Azithromycin was significantly better tolerated and caused fewer treatment-related adverse events (7.2%) than amoxicillin/clavulanate (17.1%) (P < 0.001). In response to the interview and questionnaire, parents of children treated with azithromycin noted less need for special arrangements to give medication (2.0% vs. 14.9%). Children liked the taste of azithromycin (89.2%) and did not have to be forced to take the medication (2.4%). Parents of children receiving amoxicillin/clavulanate noted that 61.8% liked the medication and 19.4% of children had to be forced to take it.. This study demonstrates that azithromycin was comparable to amoxicillin/clavulanate in achieving satisfactory clinical response rates in children with acute otitis media attending day care or school. Azithromycin was significantly better tolerated than amoxicillin/ clavulanate. Parents considered azithromycin to be significantly more convenient to administer and more acceptable to children.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child Day Care Centers; Child, Preschool; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infant; Male; Otitis Media; Schools

The objective of our study was to characterize the pharmacokinetics of azithromycin after the oral administration of multiple doses in suspension to children with acute otitis media. Thirteen children (ranging in age from 7.5 months to 5 years) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Multiple blood samples were collected after the last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The means and standard deviations for the maximum concentration of azithromycin in serum, the time to maximum concentration of azithromycin in serum, the area under the concentration-time curve (from 0 to 24 h), and the elimination half-life were 224 +/- 120 ng/ml, 1.8 +/- 0.4 h, 1,841 +/- 651 ng.h/ml, and 31.6 +/- 6.6 h, respectively. Concentrations in serum (means +/- standard deviations) at 0 h (predose) and at 24, 48, and 72 h after the final dose were 51 +/- 26, 47 +/- 21, 27 +/- 17, and 17 +/- 13 ng/ml, respectively. Thus, the once-daily administration of azithromycin resulted in sustained systemic exposure to the drug. The drug dosage regimen used in this study should lead to tissue drug concentrations exceeding the MICs for common pathogens.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Female; Humans; Infant; Male; Mass Spectrometry; Otitis Media

An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy, the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid (CA) given for ten days. A satisfactory response (cure plus improvement) was noted 10 to 14 days after the start of treatment in 199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%) amoxicillin/CA-treated children. The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum. Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin. Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated with amoxicillin/CA. No patients in the azithromycin treatment group were withdrawn from treatment, but six amoxicillin/CA patients, including two < 2 years of age, discontinued treatment prematurely because of adverse events; the difference between treatment groups was statistically significant (p = 0.0146). It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Analysis of Variance; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Infant; Male; Otitis Media; Treatment Outcome

The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media, acute sinusitis, or acute streptococcal pharyngitis or tonsillitis. Patients were assigned randomly to receive azithromycin as a single dose of 500 mg daily for three days, or clarithromycin 250 mg bid for ten days. Overall clinical efficacy was found to be similar in each treatment group at day 10-14, with a satisfactory outcome (cured or improved) in 95% of azithromycin and 96% of clarithromycin patients. Bacteriological efficacy was also similar, with eradication of the pathogen in 94% and 95% of isolates, respectively, in the azithromycin and clarithromycin groups. In otitis media, a satisfactory clinical response was seen in 97% of patients in each treatment group. Azithromycin therapy resulted in a clinical response rate of 93% in sinusitis patients, with bacteriological eradication in 93% of patients. Two patients (who were cured clinically) had persistent pathogens. Similarly, clarithromycin achieved clinical response and bacteriological eradication in 95% and 92% of sinusitis patients, respectively. Pathogens persisted in two patients with clinical cure, and in one case of clinical failure. In pharyngitis or tonsillitis, Streptococcus pyogenes was eradicated successfully in 95% of patients in both groups, and the clinical success rates were 96% and 97% for azithromycin and clarithromycin, respectively. No case of clinical failure was associated with persistence of S. pyogenes infection. At the follow-up assessment of this diagnosis group, reinfection had occurred in three (8%) azithromycin patients and one (3%) clarithromycin patient, and all but one patient remained asymptomatic. Both drugs were well-tolerated, with 8.4% of patients on azithromycin and 7.4% on clarithromycin reporting adverse events, mainly gastrointestinal. It was concluded that a three-day course of azithromycin was as effective and well-tolerated as a ten-day course of clarithromycin in adults with acute upper respiratory tract infections.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Azithromycin; Bacterial Infections; Child; Clarithromycin; Drug Administration Schedule; Erythromycin; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Otitis Media; Pharyngitis; Respiratory Tract Infections; Sinusitis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

An open randomized trial was conducted in 159 children (aged 1 to 8 years) with acute otitis media to compare the clinical efficacy of azithromycin (n = 105) and co-amoxiclav (n = 54). Azithromycin (10 mg/kg/day) was administered as a single dose for three days and co-amoxiclav was given tid for ten days at a dosage according to the manufacturer's instructions for the country. Of 103 evaluable azithromycin patients on day 3 to 5 after the start of therapy, 31 (30%) were considered cured, 67 (65%) improved and five (5%) failed compared with eight (15%) cured, 45 (83%) improved and one (2%) failed among the 54 evaluable co-amoxiclav treated patients. There was a higher number of azithromycin patients with complete resolution of symptoms at this first visit (P = 0.056). By day 10 to 12, clinical equivalence between the two treatment groups was observed with clinical cure in 86 (88%), improvement in 11 (11%) and failure in one (1%) of the 98 azithromycin patients, and in the 54 patients treated with co-amoxiclav, clinical cure was observed in 45 (83%), and improvement in nine (17%) patients. Both drugs were well tolerated and treatment related side-effects were reported in 8/105 (8%) azithromycin and 2/54 (4%) co-amoxiclav patients. In the azithromycin treatment group, these were predominantly mild to moderate gastrointestinal effects, whilst in the co-amoxiclav treatment group, both reports were of mild erythematous rash. One patient from each treatment group was withdrawn due to side-effects (azithromycin--diarrhoea and vomiting; co-amoxiclav--erythematous pruritic rash).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Child; Child, Preschool; Clavulanic Acids; Drug Combinations; Erythromycin; Female; Humans; Infant; Male; Otitis Media

In this open study, a three-day regimen of azithromycin (single daily dose of 10 mg/kg) was compared with a ten-day regimen of amoxycillin paediatric suspension (30 mg/kg/day in three divided doses; children > 20 kg received 250 mg tid daily) in 154 children (aged 2-12 years) with a clinical diagnosis of acute otitis media (13 recurrent). Full clinical, bacteriological and laboratory safety assessments were performed during and after the study. Of the 77 azithromycin patients, 61 (79%) were considered cured, 15 (19%) improved and one (1%) failed, compared with 45 (58%) cured, 28 (36%) improved and four (5%) failed among the 77 amoxycillin patients. Excluding from analysis the 13 patients with recurrent otitis media, azithromycin was found to be significantly superior to amoxycillin (P = 0.003). The incidence of side-effects was low, with only two (3%) and three (4%) patients reporting adverse events with azithromycin and amoxycillin, respectively. These were gastrointestinal in nature and of mild or moderate severity, except for one case of severe diarrhoea in the amoxycillin group. No treatment-related abnormalities in the laboratory safety tests were observed, and no patients withdrew from therapy. A three-day regimen of azithromycin was therefore shown to be more effective than, and as well tolerated as, amoxycillin in the treatment of children with acute otitis media.

Topics: Acute Disease; Amoxicillin; Azithromycin; Bacterial Infections; Child; Child, Preschool; Drug Administration Schedule; Erythromycin; Female; Humans; Male; Otitis Media; Respiratory Tract Infections

A total of 389 children (age 0.6-10.2 years) with typical signs and symptoms of acute otitis media were randomized (1:1) to treatment with either azithromycin or co-amoxiclav. The dosage schedule for azithromycin was 10 mg/kg/day, in a single daily dose, administered for three days. Co-amoxiclav was given at a dose of 13.3 mg/kg (amoxycillin equivalent) tid for ten days. Patients were evaluated 4-6 days and 12-16 days after the start of therapy. A satisfactory clinical response was reported for 93.2% of the 192 evaluable azithromycin-treated patients (144 cured, 35 improved), and for 97.3% of the 189 evaluable co-amoxiclav-treated patients (148 cured, 36 improved). Six (3.0%) relapses occurred in the azithromycin group, and four (2.1%) in the co-amoxiclav treatment group, respectively. Side-effects were recorded in a significantly fewer number of the azithromycin patients (23 of 197; 11.7%) compared with the co-amoxiclav patients (43 of 192; 22.4%, P < 0.02). Adverse events were mainly gastrointestinal in nature, with diarrhoea the most frequent complaint (32 cases with co-amoxiclav; five with azithromycin; P < 0.001). One patient from each group discontinued therapy because of treatment-related adverse events. Laboratory analyses (mainly haematological in nature) showed abnormalities in six of 100 azithromycin patients and ten of 101 co-amoxiclav patients. It was concluded that three-day, single-dose azithromycin and ten-day tid co-amoxiclav therapy have comparable clinical efficacy in paediatric patients with acute otitis media; however, there was a lower incidence of side effects in the azithromycin group.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Azithromycin; Child; Child, Preschool; Clavulanic Acids; Drug Administration Schedule; Drug Combinations; Erythromycin; Female; Humans; Infant; Male; Otitis Media

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.

Topics: Administration, Oral; Amoxicillin; Azithromycin; Child; Child, Preschool; Clavulanic Acid; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Erythromycin; Female; Follow-Up Studies; Humans; Infant; Male; Otitis Media; Otitis Media with Effusion

Describe lateral ear canal resection and bulla osteotomy with marsupialization (LECARBOM) in rabbits with otitis media (OM), and report outcomes, complications, bacteria cultured from middle ears, and their antimicrobial susceptibility testing (AST) results.. Retrospective clinical case series; single referral hospital.. Forty-two rabbits with naturally occurring OM.. Medical records (2011-2021) of rabbits with CT-confirmed OM undergoing surgery were reviewed for outcomes, complications, bacteria cultured from middle ears, and AST.. Surgery was performed on 48 ears, and outcomes determined 21 days postoperatively. All rabbits survived the procedure. Otitis externa resolved in all lop-eared rabbits. Of 29 ears with OM-associated head tilt, eight (28%) resolved, nine (31%) improved, seven (24%) remained unchanged and five (17%) worsened. Outcome was not associated with head tilt duration nor OM severity. Postoperative complications occurred in 12 (25%) cases, seven of which had wound margin dehiscence that healed by 21 days. The most frequent bacteria isolated were Pasteurella multocida (16%), Bordetella bronchiseptica (14%) and Staphylococcus aureus (14%). Bacteria were sensitive to azithromycin, marbofloxacin or enrofloxacin and resistant to penicillin.. LECARBOM is a well-tolerated surgical procedure to treat OM. It also improved or stabilized 83% of cases with head tilt and resolved all cases with otitis externa.. LECARBOM with administration of an AST-sensitive antibiotic, or azithromycin when no AST is performed, should be effective in rabbits with OM. Postsurgically, it resolves or alleviates most secondary conditions such as otitis externa, head tilt and facial nerve paralysis.

Topics: Animals; Azithromycin; Bacteria; Blister; Ear Canal; Osteotomy; Otitis Externa; Otitis Media; Rabbits; Retrospective Studies

The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM).. We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was the antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age, and antibiotic duration.. Among the 1 051 007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% were prescribed amoxicillin-clavulanate, 20.6% were prescribed cefdinir, and 9.3% were prescribed azithromycin. Most prescriptions (93%) were for 10 days, and 98% were filled within 1 day of the medical encounter. Treatment failure and recurrence occurred in 2.2% (95% CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8), amoxicillin-clavulanate (11.3%; 11.1, 11.5), cefdinir (10.0%; 9.8, 10.1), and azithromycin (9.8%; 9.6, 10.0).. Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Cefdinir; Child; Humans; Infant; Otitis Media; Retrospective Studies; Treatment Outcome

Topics: Acetylcysteine; Anti-Bacterial Agents; Azithromycin; Humans; Otitis Media; Otitis Media with Effusion

Healthcare claims are underutilized to identify factors associated with high outpatient antibiotic use.. We evaluated ambulatory encounter claims of Medicaid-insured children in 34 Ohio counties in 2014. Rates of total antibiotic and azithromycin prescriptions dispensed were determined by county of patient residence. Standardized treatment rates by county were estimated for uncomplicated upper respiratory tract encounters (acute otitis media, pharyngitis, sinusitis, presumed viral infection) after adjusting for patient age and encounter provider type. Uncomplicated encounters included healthy children at initial presentation of illness. Adjusted odds of treatment were calculated for patient age, provider type, and county characteristics (rural vs metropolitan; poverty rate).. Retail pharmacies dispensed 255291 antibiotics to this cohort in 2014. More than 25% were to children <3 years. County rates of total antibiotic and azithromycin prescriptions dispensed were 530.4-1548.3 and 57.3-378.7 per 1000 person-years, respectively. Of 246866 uncomplicated upper respiratory tract encounters, antibiotics were dispensed (within 3 days) in 46.1%. Presumed viral infection accounted for 18.5% of antibiotics. Standardized treatment rates by county ranged widely from 35.9% (95% confidence interval [CI], 33.3%-38.5%) to 63.2% (95% CI, 61.5%-64.9%). Compared to encounters with pediatricians, adjusted odds ratio of treatment was 2.02 (95% CI, 1.96-2.07) for family physicians and 1.74 (95% CI, 1.68-1.79) for nurse practitioners. Residence in rural or high-poverty counties increased odds of treatment.. Healthcare claims were useful to identify populations and providers with high antibiotic use. Claims data could be considered to track and report antibiotic prescribing frequency, especially where electronic medical records are not available.

Topics: Adolescent; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Child; Child, Preschool; Cohort Studies; Drug Prescriptions; Female; Humans; Infant; Male; Medicaid; Multivariate Analysis; Otitis Media; Outpatients; Practice Patterns, Physicians'; Retrospective Studies; Sinusitis; United States

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Child; Humans; Infant; Otitis Media

Topics: Anti-Bacterial Agents; Azithromycin; Child; Fatal Outcome; Female; Humans; Long QT Syndrome; Medical Order Entry Systems; Medication Errors; Otitis Media; Sinusitis

Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (10(4)-10(5) colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria.

Topics: Animals; Azithromycin; Disease Models, Animal; Haemophilus Infections; Haemophilus influenzae; Heterozygote; Immunity, Innate; Inflammation; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Microspheres; Mutation; Otitis Media; Signal Transduction; Stem Cells

Otitis media (OM) is an extremely common pediatric ailment caused by opportunists that reside within the nasopharynx. Inflammation within the upper airway can promote ascension of these opportunists into the middle ear chamber. OM can be chronic/recurrent in nature, and a wealth of data indicates that in these cases, the bacteria persist within biofilms. Epidemiological data demonstrate that most cases of OM are polymicrobial, which may have significant impact on antibiotic resistance. In this study, we used in vitro biofilm assays and rodent infection models to examine the impact of polymicrobial infection with Moraxella catarrhalis and Streptococcus pneumoniae (pneumococcus) on biofilm resistance to antibiotic treatment and persistence in vivo. Consistent with prior work, M. catarrhalis conferred beta-lactamase-dependent passive protection from beta-lactam killing to pneumococci within polymicrobial biofilms. Moreover, pneumococci increased resistance of M. catarrhalis to macrolide killing in polymicrobial biofilms. However, pneumococci increased colonization in vivo by M. catarrhalis in a quorum signal-dependent manner. We also found that co-infection with M. catarrhalis affects middle ear ascension of pneumococci in both mice and chinchillas. Therefore, we conclude that residence of M. catarrhalis and pneumococci within the same biofilm community significantly impacts resistance to antibiotic treatment and bacterial persistence in vivo.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Biofilms; Chinchilla; Disease Models, Animal; Drug Resistance, Bacterial; Mice; Microbial Interactions; Moraxella catarrhalis; Nasopharynx; Otitis Media; Quorum Sensing; Streptococcus pneumoniae

To investigate possible ototoxic effects of topical azithromycin (AZ) in the guinea pig.. A prospective, controlled animal study.. The University of Texas Southwestern Medical Center at Dallas.. Twenty-three pigmented guinea pigs were given single, unilateral middle ear applications of a solution containing 3% (n = 3), 2% (n = 5), 1% (n = 5), or 0.5% (n = 5) AZ or saline (n = 5). The contralateral ear served as the untreated control.. The animals were observed for behavioral changes for 2 weeks and then humanely killed. The ears were processed for anatomical evaluation. Morphologic changes were analyzed by quantitation of middle ear changes and cochlear inner and outer hair cell loss. Statistical analysis was performed to examine effects by dose.. Analysis revealed extensive middle and inner ear changes associated with all formulations of AZ. Moderate correlation was found between the extent of middle ear changes and AZ concentration (r(2) = 0.59), whereas a strong correlation was seen between inner ear damage and AZ concentration (r(2) = 0.94). Both inner and outer hair cells were affected, with inner hair cell damage consistently greater than outer hair cell damage.. The results of this study demonstrate that ototopical AZ can cause middle ear changes and significant hair cell loss in the guinea pig. This finding, together with previous clinical reports, indicates that topical AZ should be used with caution in the clinical setting.

Topics: Animals; Azithromycin; Ear, Inner; Ear, Middle; Guinea Pigs; Hair Cells, Auditory; Linear Models; Male; Otitis Media; Prospective Studies

Azithromycin (AZM) is widely used for respiratory tract infections and otitis media because of its activity against Haemophilus influenzae and atypical pathogens, and its ease of administration. Although leukopenia is the one of the most frequent AZM-related laboratory abnormalities in children, agranulocytosis has not been reported in adults. Here, we present the case of an 81-year-old man with agranulocytosis following AZM-treatment for acute otitis media. He developed febrile neutropenia and granulocyte colony-stimulating factor and cefepim were administered. All his symptoms and absolute neutrophil counts were recovered within 7 days after admission. Physicians must be vigilant in identifying drug-induced neutropenia in AZM-treated patients because early detection can decrease the severity and prevent mortality.

Topics: Acute Disease; Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Azithromycin; Humans; Male; Otitis Media

Authorities have suggested restriction of azithromycin use as a principal strategy to contain the spread of azithromycin-nonsusceptible Streptococcus pneumoniae (ANSP). In 83 children persistently colonized by pneumococcus during and after treatment of acute otitis media, 17 acquired a new strain, 9 of which were less susceptible to azithromycin than the original isolate. New appearance of ANSP was documented after both beta-lactam and azithromycin exposure. ANSP is likely to disseminate even with significant reduction of azithromycin use unless other antibiotic use is decreased as well.

Topics: Azithromycin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Otitis Media; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

Hearing loss as a possible side effect of azithromycin has been recognized since 1994. Most reports suggesting a link between sensorineural hearing loss (SNHL) and this drug have been in association with prolonged doses for treatment of Mycobacterium lung disease. Mild-moderate, gradual, and reversible SNHL in the speech frequencies has been most often reported.. We describe irreversible SNHL in a patient in association with low-dose oral azithromycin prescribed for acute otitis media. We summarize the available evidence, including a systematic literature review, in support of a possible causal association between SNHL and low-dose azithromycin therapy.. Physicians should be aware of the potential for even low-dose, oral azithromycin to cause irreversible SNHL as a serious adverse drug reaction in some patients.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Female; Hearing Loss, Sensorineural; Humans; Middle Aged; Otitis Media

Asia has experienced a striking incidence of infection by highly resistant pneumococi containing both principal macrolide resistance determinants, namely, the mef efflux pump and the erm ribosomal methylase. mef/erm-containing pneumococci have not been identified in significant numbers in North America.. Pneumococci were isolated as part of a larger study in Cleveland, OH examining colonization patterns among children randomized to 1 of 4 outpatient antibiotics for acute otitis media. Azithromycin-resistant organisms were tested for the presence of mef and erm sequences by polymerase chain reaction. The clonal relationship of pneumococci containing both genes was determined by pulsed field gel electrophoresis and multilocus sequence testing. Selected characteristics of children harboring mef/erm-containing organisms were compared with other participants of the larger study.. Of 221 children colonized by pneumococci, 17 (7.7%) were colonized with an organism containing both determinants. All mef/erm-positive organisms demonstrated azithromycin minimum inhibitory concentrations > or =256 microg/mL and were coresistant to all other agents tested. The mef/erm-containing organisms were serotype 19A and 19F, all but 1 of which manifested similar pulsed field gel electrophoresis patterns. Multilocus sequence testing analysis indicated a relationship to the Taiwan-14 macrolide-resistant strain that has spread throughout Eastern Asia. More than one-third of children colonized by a mef/erm-containing organism had received > or =1 dose of conjugate pneumococcal vaccine, a significantly higher proportion than children carrying less resistant organisms (P< 0.01). No other characteristics distinguished children harboring a mef/erm-containing pneumococcus from other children enrolled in the larger study.. Clonally related mef/erm-containing serogroup 19 pneumococci were prominent among otherwise healthy children in a North American metropolitan area. Our findings suggest that spread of these organisms may be poorly contained by immunization.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Child; Child, Preschool; DNA Fingerprinting; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Humans; Infant; Membrane Proteins; Methyltransferases; Microbial Sensitivity Tests; Molecular Epidemiology; Ohio; Otitis Media; Pneumococcal Infections; Polymerase Chain Reaction; Sequence Analysis, DNA; Serotyping; Streptococcus pneumoniae

Population-based studies may give results different from randomized clinical trials assessing the efficacy of antibiotics.. To determine the effectiveness of amoxicillin, azithromycin, cefprozil and clarithromycin in the treatment of acute otitis media (AOM) in children.. Using Quebec Health Insurance databases (RAMQ), we selected a cohort of children aged < or = 6 years, with a first episode of AOM between 1999 and 2002. The index AOM was defined as a medical service claim with a diagnosis of AOM and an antibiotic dispensation in the following 72 hours. Failures were defined as a new antibiotic dispensation, a hospitalization or outpatient visit for complications related to AOM in the 30 days after the index AOM. Data were analyzed using logistic regression.. Overall, 12,693 failures occurred among 60,513 first episodes of AOM. Azithromycin was the only antibiotic that was associated with a decreased risk of failure overall, when compared to amoxicillin (OR 0.88, 95% CI: 0.82, 0.94). However in the first 3 days of treatment (n = 680), azithromycin was more associated with treatment failure (OR 1.6, 95% CI: 1.3, 2.0). Compared to amoxicillin, post-therapy failures (n = 9387) were more likely to occur with cefprozil (OR 1.2, 95%CI: 1.2, 1.3) but were less with azithromycin (OR 0.8 95% CI: 0.8, 0.9).. Azithromycin had the lowest risk of failure 30 days after the onset of treatment but an increased risk of failure during the first few days of treatment. Amoxicillin remains an effective first-line drug for treating first AOM episodes.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefprozil; Cephalosporins; Child; Child, Preschool; Clarithromycin; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Otitis Media; Quebec; Risk Factors; Time Factors; Treatment Outcome

Topics: Acute Disease; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefprozil; Ceftriaxone; Cephalosporins; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Otitis Media; Risk Assessment; Sensitivity and Specificity; Streptococcus pneumoniae

Topics: Acute Disease; Amoxicillin; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Male; Otitis Media; Prospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Infant; Otitis Media; Randomized Controlled Trials as Topic; Recurrence; Reproducibility of Results

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Drug Therapy, Combination; Haemophilus influenzae; Humans; Otitis Media; Research Design; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Drug Therapy, Combination; Haemophilus influenzae; Humans; Otitis Media; Research Design; Streptococcus pneumoniae; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Multiple, Bacterial; Drug Utilization; Erythromycin; Humans; Microbial Sensitivity Tests; Otitis Media; Pneumococcal Infections; South Africa; Streptococcus pneumoniae; Treatment Outcome

Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen.

Topics: Acute Disease; Animals; Azithromycin; Chinchilla; Dose-Response Relationship, Drug; Haemophilus Infections; Haemophilus influenzae; Otitis Media

The ability of the recently licensed 7-valent pneumococcal conjugate vaccine to cover isolates that cause otitis media, especially drug-resistant ones, was assessed using 500 recently obtained US isolates. Of these isolates, 418 (84%) belonged to vaccine-related serogroups, whereas 82 (16%) belonged to non-vaccine-related serogroups. Serotype 3 accounted for 48 (59%) of the non-vaccine-related serogroups. In addition, 93% of the isolates from patients < or =3 years of age belonged to serotypes that were included in or related to the heptavalent vaccine, compared with 49% of the isolates from older patients (P=.001). Most of the isolates (98%-100%) that were resistant to the antimicrobial agents tested were covered by the heptavalent vaccine, including 95.1% of the isolates from patients <2 years of age. The 7-valent pneumococcal conjugate vaccine could therefore potentially provide protection against all but 1 (type 3) of the common otitis media-associated pneumococcal serogroups identified in this study as well as against 98% of antibiotic-resistant isolates.

Topics: Adolescent; Adult; Aged; Amoxicillin; Azithromycin; Child; Child, Preschool; Clindamycin; Cross-Sectional Studies; Drug Resistance, Bacterial; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Meningococcal Vaccines; Microbial Sensitivity Tests; Middle Aged; Otitis Media; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate

Topics: Acute Disease; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cefaclor; Cephalosporins; Clinical Trials as Topic; Humans; Otitis Media; Outcome Assessment, Health Care; Time Factors; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Humans; Otitis Media; Pneumonia, Bacterial; Soft Tissue Infections; Streptococcal Infections; Streptococcus pyogenes; Whooping Cough

Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment.. To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM).. Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated.. A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving.. A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.

Topics: Acute Disease; Anti-Bacterial Agents; Azithromycin; Carrier State; Child, Preschool; Drug Resistance, Microbial; Female; Humans; Infant; Lactams; Male; Microbial Sensitivity Tests; Nasopharynx; Otitis Media; Pneumococcal Infections; Prospective Studies; Streptococcus pneumoniae

Azithromycin reaches high concentrations in phagocytic and other host cells, suggesting that they may transport this agent to specific sites of infection. Models of localized infection (Haemophilus influenzae middle ear infection in gerbils, Streptococcus pyogenes implanted contaminated paper disc and Streptococcus pneumoniae pneumonia in mice) that induced severe inflammatory response after challenge were used to explore this hypothesis. Animals were given a single 100 or 50 mg/kg po dose of azithromycin at various times from 2 to 120 h following introduction of a pathogen or sterile medium. When azithromycin was given during a period of little or no inflammation, there was marginal difference between concentrations found in infected or non-infected sites (bulla, disc, lung). However, when the compound was given during a period of inflammation, considerably higher drug concentrations were found in infected sites than in non-infected sites at 5-24 h after dosing (0.38-0.44 mg/c compared with 0.07-0.14 mg/L of bulla wash; 1.01-1.75 micrograms compared with < or = 0.01-0.03 microgram at the disc site; 1.72-5.28 mg/kg compared with 0.7-1.53 mg/kg of lung). When the observation periods were extended to include 48, 56 or 96 h after dosing, the ratio of azithromycin infection site concentration: serum concentration steadily increased with time in all model systems (middle ear, implanted disc and pneumonia), reflecting the maintenance of concentrations at the sites of infection, while serum concentrations declined. Bioassay of cell pellets and supernatants, obtained from pooled bulla washes of gerbils treated with azithromycin during a period of inflammation, revealed that cellular components accounted for about 75% of the azithromycin detected. These data show that increased azithromycin concentrations occur at sites of localized infection. This correlates with the presence of inflammation and is associated with the cellular components of the inflammatory response. Therefore, phagocytes may be important vehicles for delivering azithromycin to and sustaining azithromycin concentrations at sites of infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Blister; Female; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Lung; Male; Mice; Otitis Media; Phagocytes; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

The prevalence of penicillin-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae in otitis media infections is increasing; emergence of these pathogens has complicated treatment.. To evaluate the incidence of penicillin resistance and the in vitro activity of amoxicillin/clavulanate, cefaclor, loracarbef, cefixime, trimethoprim/sulfamethoxazole, azithromycin and clarithromycin in S. pneumoniae isolates. The in vitro activity of azithromycin, clarithromycin and cefaclor was also evaluated in beta-lactamase-positive and -negative isolates of H. influenzae.. Bacterial isolates of S. pneumoniae and H. influenzae were obtained by tympanocentesis and subsequent culture of middle ear effusion from children with acute otitis media enrolled in a multicenter trial. Susceptibility to test agents was assessed by disk diffusion and broth dilution techniques with criteria established by the National Committee for Clinical Laboratory Standards.. Nineteen (31%) of the 61 S. pneumoniae isolates were resistant to penicillin. A significantly lower percentage of the S. pneumoniae isolates were resistant to azithromycin (16%) and clarithromycin (11%) than to penicillin, amoxicillin/ clavulanate, cefaclor, loracarbef or cefixime (31% in all cases). Azithromycin was also more active than cefaclor and significantly more active than clarithromycin against the 55 H. influenzae isolates.. The susceptibility of resistant and nonresistant strains of S. pneumoniae to azithromycin and clarithromycin and of isolates of H. influenzae to azithromycin, coupled with penetration of azithromycin into the middle ear, may provide a significant advantage in the treatment of otitis media.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Child; Clarithromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Incidence; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Resistance, Microbial; Female; Humans; Infant; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

Azithromycin activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic. The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured. Recurrences were never observed. Azithromycin proved remarkably effective for treatment of acute respiratory infections and otitis media in children. Tolerability and therapeutic compliance were excellent.

Topics: Acute Disease; Azithromycin; Bacteria; Bronchitis; Child; Child, Preschool; Evaluation Studies as Topic; Female; Humans; Infant; Male; Otitis Media; Pharyngitis; Respiratory Tract Infections; Rhinitis; Sinusitis; Tonsillitis; Tracheitis

Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Models, Animal; Endocarditis, Bacterial; Erythromycin; Female; Gerbillinae; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Otitis Media; Pneumococcal Infections; Pneumonia; Rats; Roxithromycin; Streptococcal Infections; Streptococcus pyogenes

The efficacy of an investigational macrolide, azithromycin, in the treatment of acute otitis media consequent to an infection by a strain of beta-lactamase-producing Haemophilus influenzae, was evaluated using the chinchilla animal model. The results indicate that the azithromycin high-dosage (30 mg/kg/d) group has a significantly higher rate for effusion sterilization and resolution as compared with the other treatment groups. Unique pharmacokinetic properties of this investigational antimicrobial were demonstrated. Clinical trials using azithromycin for the treatment of upper respiratory tract infections, including otitis media, are warranted.

Topics: Acute Disease; Ampicillin; Animals; Azithromycin; Chinchilla; Disease Models, Animal; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Otitis Media