Azithromycin In Children Research Articles

Multi-center study of the combination of traditional Chinese medicine and western methods treatment in the mycoplasma pneumoniae lower respiratory infection in children

Objective To evaluate the effectiveness of traditional drug(oral feirekechuan liquid for children) combined Azithromycin for children with Mycoplasma pneumoniae(MP) lower respiratory infection, and to provide optional method for the treatment of MP pneumonia with the combination approach. Methods This study was designed as prospective, randomized, open, paralleled, positive medicine controlled multi-center clinical trial.During Aug.2012 to Aug.2013, patients were included in the study who were suspected of MP infection in pediatric clinics and wards according to the inclusion criteria.All patients were randomly divided into two groups: treatment group(oral feirekechuan liquid for children plus Azithromycin) and control group(Azithromycin). Throat swab and serum specimens were obtained from patients, and also clinical data of all children were collected.MP DNA was detected by the nested PCR method with primers sets for amplification of the binding site of erythromycin at 23S rRNA.ELISA or particle agglutination method was applied to detect MP antibodies in serum.Clinical information of the patients was analyzed and their MP DNA was detected and/or MP-antibodies were positive. Results Seventy-nine patients with perfect clinical data and Nested PCR positive and/or MP-antibodies positive were analyzed.Thirty-seven patients received traditional chinese drug and Azithromycin(treatment group) and 42 patients received only Azithromycin(control group). There were no statistical significance in the sex, age, patients' fundamental conditions between the two groups.After treatment, in the treatment group the time of the fever was shorter than the control group [(5.14±1.40) d vs(6.12±2.45) d, P=0.014]. Also, the treatment group took less time for coughing reduction[(6.00±1.38) d vs (6.92±1.63) d, P=0.026]and disappearing[(8.06±2.16) d vs (9.83±2.60) d, P=0.036]. Conclusions Oral feirekechuan liquid for children combined with Azithromycin is more effective than Azithromycin used alone for the treatment of mycoplasma pneumoniae infection in children, and can be used as complementary medicine. Key words: Combination of traditional Chinese medicine and western methods; Oral feirekechuan liqnid for children; Mycoplasma pneumoniae infection; Clinical manifestation

Pulmonary exacerbations in CF patients with early lung disease

Current definitions of pulmonary exacerbation (PE) in cystic fibrosis are based on studies in participants with significant lung disease and may not reflect the spectrum of findings observed in younger patients with early lung disease. We used data from a recent trial assessing the efficacy of azithromycin in children to study signs and symptoms associated with PEs and related changes in lung function and weight. While increased cough was present in all PEs, acute weight loss and reduction in oxygen saturation were not observed. Changes in lung function did not differ between subjects who did experience a PE and those who were exacerbation-free. Cough was the predominant symptom in CF patients with early lung disease experiencing a PE. There was no significant difference in mean 6-month change in lung function or weight among subjects with one or more exacerbations and those without an exacerbation.

What is new in the prevention of atopy and asthma?

Increasing understanding of mechanisms and influencing factors in the development of uncontrolled inflammatory responses in atopy and asthma should serve for the introduction of new preventive measures. This review tries to present the current state of the art and resumes that until now, no really effective concept can be offered to families at risk. In addition to modified feeding regimes (hydrolysed formula feeding in infancy), timing of the introduction of solids (avoidance of allergens versus early induction of tolerance), immune modulation using prebiotics or probiotics, a new target of potential intervention could be the human microbiome as a key player in the development of inflammatory diseases such as allergy and asthma. However, during the last 5 years, this concept could not yet be verified in interventional trials. There are new trials ongoing, studying the effect of microbial compounds in early infancy, vitamin D and polyunsaturated fatty acid supplementation during late pregnancy and the effect of azithromycin in children with recurrent wheeze. Results are to be expected within the next couple of years. New data on multifaceted intervention and the analysis of the human microbiome are to be expected. The recommendation for atopy and asthma prevention still focuses on avoidance of tobacco smoke exposure and food allergens during the first 4 months of life and feeding of hydrolysed formula if breast-feeding is not possible in high-risk infants, potentially early feeding of prebiotic sugars and/or certain strains of probiotic bacteria or bacterial compounds in certain subpopulations.

Management of the Chronically Inflamed Pediatric Airway

Objective: To examine our initial experience with the use of azithromycin in children with airway stenosis and chronically inflamed airways. Method: This retrospective study examined 20 children with airway stenosis and chronically inflamed airways. Patients tested negative for eosinophilic esophagitis and gastroesophageal reflux and took azithromycin (10 mg/kg) 3 times per week for at least a 1-month period. Outcomes were status of airway inflammation after azithromycin and decision to intervene on airway stenosis. Results: The mean age was 3.6 years (range 0.9-8.0) with 13 females and 7 males. Diagnoses included subglottic stenosis (85%), tracheal stenosis (5%), bronchial stenosis (5%), and bilateral vocal cord paralysis (5%). Mean duration of azithromycin therapy was 116.6 days (range 42-192). Airway inflammation improved in 14 patients (70%) allowing successful airway intervention in 12 patients. Two did not undergo surgery due to reasons other than airway inflammation. Six patients had persistent inflammation, 5 of whom are currently being observed. Conclusion: Children with airway stenosis and chronic inflammation pose significant challenges for the airway surgeon. Our initial experience suggests that azithromycin can reduce airway inflammation, allowing one to proceed with surgical intervention. Further studies evaluating azithromycin are warranted.

Two-Day Dosing versus One-Day Dosing of Azithromycin in Children with Severe Trachoma in Tanzania

Purpose: To determine whether 2-day dosing of azithromycin may improve the efficacy of azithromycin dosing in children with severe trachoma.Methods: Fifty children with severe trachoma (defined as either trachoma intense or follicular trachoma with ten or more follicles) were enrolled from five villages in Kongwa, Tanzania. Enrollment occurred within 1 month and within the same district as the historical control population of 99 children with severe trachoma, all of whom received 1-day dosing. Baseline data on age, sex, and trachoma status were obtained, and swabs for determination of Chlamydia trachomatis were taken. All 50 children received 20 mg/kg azithromycin daily for 2 days, which was directly observed. Children were followed up at 6 weeks for trachoma and infection. The laboratory was masked to treatment assignment.Results: Baseline characteristics were similar between the treatment group and the control group. A total of 1/46 (2.2%) of children in the treatment group were polymerase chain reaction (PCR)-positive at 6 weeks, a 96.3% reduction from baseline, compared to 13/96 (13.5%) in the historical control group, an 89.4% reduction. This difference was statistically significant. However when modeled using logistic regression and accounting for age, gender, weight, and baseline percent PCR positivity, the difference was not significant. Prevalence of clinical trachoma did not differ between the groups at 6 weeks.Conclusion: For children with severe trachoma, a randomized controlled trial of 2-day versus 1-day treatment may be warranted.

Open‐label, follow‐on study of azithromycin in pediatric patients with CF uninfected with Pseudomonas aeruginosa

We previously performed a randomized placebo-controlled trial to examine the effects of azithromycin in children and adolescents 6-18 years of age with cystic fibrosis uninfected with Pseudomononas aeruginosa and demonstrated that while azithromycin did not acutely improve pulmonary function, azithromycin-reduced pulmonary exacerbations, decreased the initiation of new oral antibiotics, and improved weight gain. We now report the results of the open-label, follow-on study to assess durability of response to azithromycin and continued safety and tolerability. Eligible participants were enrolled in a 24-week open-label study of azithromycin to compare efficacy and safety endpoints during the placebo-controlled trial versus open-label study in two groups: participants initially on azithromycin continued azithromycin (azithromycin-azithromycin) and participants initially on placebo who then received azithromycin (placebo-azithromycin). As in the placebo-controlled trial, the azithromycin dose in the open-label study was 250 mg Monday-Wednesday-Friday for participants weighing 18-35.9 kg and 500 mg Monday-Wednesday-Friday for participants weighing 36 kg or greater. Of 174 eligible participants, 146 (83.9%) enrolled in the open-label study. No significant improvements in lung function were observed within either group. There were no differences in outcomes in the placebo-azithromycin group during the placebo-controlled versus open-label phase. The azithromycin-azithromycin group had comparable odds of experiencing an exacerbation during the two phases (OR 1.6, CI(95) 0.8, 3.0) and stable weight gain, but new oral antibiotics were initiated more frequently during the open-label study (OR 1.9, CI(95) 1.0, 3.5). In both groups, adverse event rates were comparable during the placebo-controlled and open-label study and treatment-emergent pathogens were rare. During the open-label study, we observed continued durability of treatment response to azithromycin, as measured by pulmonary exacerbations and continued weight gain, although use of oral antibiotics increased. There were no new safety concerns. Currently available data suggest that azithromycin reduces exacerbations and improves weight gain for 6-12 months among children and adolescents with CF uninfected with P. aeruginosa.

Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A randomized controlled trial

Background Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration are not very well studied in children with CF. Methods A randomized controlled trial was conducted to compare the effect of two doses of azithromycin (5 mg/kg/day and 15 mg/kg/day) on FEV 1 and pulmonary exacerbations in children with cystic fibrosis. Enrolled children were randomly allocated to receive daily azithromycin (5 mg/kg/day or 15 mg/kg/day) for 6 months. Clinical assessment and FEV 1 measurement were performed monthly. Results 56 children (28 in high dose group and 28 in low dose group) were enrolled. 47 (24 and 23 children in low and high dose groups) completed 12 months of follow up. There was no difference in clinical scores, FEV 1, pulmonary exacerbation rates between two groups at baseline, 6 months and at 12 months. Per protocol analysis revealed that pulmonary exacerbation increased after discontinuing AZM and there was significantly more increase after 12 months of enrolment in children getting high dose azithromycin. There was no improvement in FEV 1 in either group at the end of treatment period. Children tolerated daily low as well as high dose AZM well for 6 months. There was no significant side effect of azithromycin. Conclusion In this randomized controlled trial, we did not find differences in the effect of 2 doses (5 mg/kg/day or 15 mg/kg/day) of AZM on change in percentage predicted FEV 1, clinical scores, Pseudomonas colonization rates, pulmonary exacerbations and need for antibiotics. There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6 months after discontinuing azithromycin.

Index of Suspicion

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114 An audit of the clinical impact of oral azithromycin in children with chronic Pseudomonas airway infection

114 An audit of the clinical impact of oral azithromycin in children with chronic Pseudomonas airway infection

Bacterial etiology of acute otitis media and clinical efficacy of amoxicillin–clavulanate versus azithromycin

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.

A comparison of 5 days of therapy with cefdinir or azithromycin in children with acute otitis media: A multicenter, prospective, single-blind study

Background:Short-course therapy for acute otitis media (AOM) improves adherence and may reduce secondary bacterial resistance. Methods: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). Results: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 (≤7% each). Conclusions: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.

Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial

The macrolide antibiotic azithromycin has anti-inflammatory properties potentially beneficial in cystic fibrosis. Since findings of open pilot studies seemed to show clinical benefit, we undertook a formal trial. 41 children with cystic fibrosis, aged 8-18 years, and with a median forced expiratory volume in 1 s (FEV1) of 61% (range 33-80%) participated in a 15-month randomised double-blind, placebo-controlled crossover trial. They received either azithromycin (bodyweight < or =40 kg: 250 mg daily, >40 kg: 500 mg daily) or placebo for 6 months. After 2 months of washout, the treatments were crossed over. The primary outcome was median relative difference in FEV1 between azithromycin and placebo treatment periods. Sputum cultures, sputum interleukin 8 and neutrophil elastase, exercise testing, quality of life, antibiotic use, and pulmonary exacerbation rates were secondary outcome measures. Side-effects were assessed by pure tone audiometry and liver function tests. Analysis was by intention-to-treat. Median relative difference in FEV1 between azithromycin and placebo was 5.4% (95% CI 0.8-10.5). 13 of 41 patients improved by more than 13% and five of 41 deteriorated by more than 13% (p=0.059). Forced vital capacity and mid-expiratory flow did not significantly change overall. 17 of 41 patients had 24 fewer oral antibiotic courses when on azithromycin than when taking placebo, and five had six extra courses (p=0.005). Sputum bacterial densities, inflammatory markers, exercise tolerance, and subjective well-being did not change. There were no noticeable side-effects. A 4-6-month trial of azithromycin is justified in children with cystic fibrosis who do not respond to conventional treatment. The mechanism of action remains unknown.

Azithromycin in children: A critical review of the evidence

Background: Azithromycin is a macrolide antibiotic that can be dosed once daily. In the last decade, the body of literature concerning the clinical applications of azithromycin has grown rapidly, leading to improved understanding as well as new questions about the role of this drug in the treatment of adult and pediatric infections. Objective: This review explores the use of azithromycin in the treatment of pediatric infections. Methods: We conducted a MEDLINE literature search to identify pertinent English-language studies of azithromycin published between 1987 and 2001. Results: The use of azithromycin in the treatment of acute Streptococcus pyogenes pharyngotonsillitis, acute otitis media, community-acquired pneumonia, pertussis, skin and soft tissue infections, Mycobacterium avium complex (MAC), trachoma, typhoid fever, cat-scratch disease, cryptosporidiosis, and legionnaires' disease has been studied in clinical trials. Conclusions: Azithromycin is indicated as a first-line treatment for respiratory tract infections caused by Legionella species, Mycoplasma pneumoniae, and Chlamydia pneumoniae, and as empiric therapy for community-acquired pneumonia in older children and adolescents who are deemed appropriate for outpatient oral therapy. Azithromycin in a single dose is an excellent treatment for chlamydia cervicitis/urethritis and for trachoma and has demonstrated efficacy in prophylaxis and treatment of disseminated MAC infections in children who have AIDS. Azithromycin may be considered as an alternative in the treatment of skin and soft tissue infections, although local patterns of resistance of pathogens must be considered in its selection.

Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media

To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow-up between Days 22 and 28. Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (13 of 19) [corrected], P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture-positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow-up. Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.

Clinical tolerability and safety of azithromycin in children

Azithromycin oral suspension was administered to 1928 children aged 6 months to 15 years in Phase II/III United States clinical trials. Infections treated included acute otitis media (n =1150) and streptococcal pharyngitis (n = 754). Predominant dosage regimens were 30 mg/kg over 5 days for otitis media and 60 mg/kg over 5 days for pharyngitis. Treatment-related side effects occurred in 9.9% of azithromycin patients, compared with 18.4% of comparator patients. The only azithromycin side effects with an incidence 1% were diarrhea (3.1%), vomiting (2.5%), loose stools (1.0%) and abdominal pain (1.9%). Both azithromycin regimens were well tolerated. Only 0.9% of multidose azithromycin recipients discontinued therapy because of side effects, compared with 2.2% of comparators. Marked laboratory test abnormalities were rare and of equal incidence to comparators, and no patient discontinued treatment because of abnormal laboratory values. Azithromycin was well tolerated in the presence of a variety of concurrent conditions and concomitant medications.

Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) 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. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.