zithromax and Communicable-Diseases

Mass drug administration (MDA) with azithromycin may reduce under-5 child mortality (U5M) in sub-Saharan Africa. Here, we conducted a pooled analysis of all published cluster-randomized trials evaluating the effect of azithromycin MDA on child mortality. We pooled data from cluster-randomized trials randomizing communities to azithromycin MDA versus control. We calculated mortality rates in the azithromycin and control arms in each study, and by country for multisite studies including multiple countries. We conducted a two-stage individual community data meta-analysis to estimate the effect of azithromycin for prevention of child mortality. Three randomized controlled trials in four countries (Ethiopia, Malawi, Niger, and Tanzania) were identified. The overall pooled mortality rate was 15.9 per 1,000 person-years (95% confidence interval [CI]: 15.5-16.3). The pooled mortality rate was lower in azithromycin-treated communities than in placebo-treated communities (14.7 deaths per 1,000 person-years, 95% CI: 14.2-15.3 versus 17.2 deaths per 1,000 person-years, 95% CI: 16.5-17.8). There was a 14.4% reduction in all-cause child mortality in communities receiving azithromycin MDA (95% CI: 6.3-21.7% reduction,

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child Mortality; Child, Preschool; Communicable Disease Control; Communicable Diseases; Humans; Infant; Infant Mortality; Mass Drug Administration

Two of the most significant changes in the field of infectious disease management during the last few decades are the emergence of atypical and/or new pathogens that may have devastating consequences and the re-emergence of well-recognised organisms that have acquired antimicrobial resistance through a variety of mechanisms. Erythromycin, the prototype macrolide, was originally marketed approximately five decades ago as a useful alternative agent in the treatment of patients allergic to beta-lactam antibiotics. While clinically useful, its pharmacokinetic and adverse-event profile limited the use of erythromycin to these individuals. Enhancements of the macrolide structure circumvented many of the limitations of erythromycin and resulted in the development of azithromycin and clarithromycin. The clinical uses of clarithromycin and azithromycin are substantially wider than erythromycin due to the wide spectra of activity against the atypical and newer pathogens. In addition, these agents are well-tolerated and have a pharmacokinetic profile that allows once- or twice-daily administration. Studies also indicate that the more common of the two mechanisms of macrolide resistance in the US and Canada imparts only low-level resistance. The multitude of studies substantiating clinical as well as bacteriological success with these two agents indicates that, when used appropriately, they will stand the test of time and continue to be useful antimicrobial agents.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Biological Availability; Child; Clarithromycin; Communicable Diseases; Drug Resistance, Bacterial; Erythromycin; Half-Life; Humans; Metabolic Clearance Rate

Maternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised clinical trial conducted in a single site in The Gambia showed that treatment with an oral dose of 2 g azithromycin versus placebo for all women in labour reduced certain maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. In a large, multinational randomised trial, we will evaluate the impact of azithromycin given in labour to improve maternal and newborn outcomes.. This randomised, placebo-controlled, multicentre clinical trial includes two primary hypotheses, one maternal and one neonatal. The maternal hypothesis is to test whether a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labour will reduce maternal death or sepsis. The neonatal hypothesis will test whether this intervention will reduce intrapartum/neonatal death or sepsis. The intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, compared with a single intrapartum oral dose of an identical appearing placebo. A total of 34 000 labouring women from 8 research sites in sub-Saharan Africa, South Asia and Latin America will be randomised with a one-to-one ratio to intervention/placebo. In addition, we will assess antimicrobial resistance in a sample of women and their newborns.. The study protocol has been reviewed and ethics approval obtained from all the relevant ethical review boards at each research site. The results will be disseminated via peer-reviewed journals and national and international scientific forums.. NCT03871491 (https://clinicaltrials.gov/ct2/show/NCT03871491?term=NCT03871491&draw=2&rank=1).

Topics: Azithromycin; Communicable Diseases; Developing Countries; Female; Humans; Infant, Newborn; Multicenter Studies as Topic; Perinatal Death; Randomized Controlled Trials as Topic; Sepsis

Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality.. In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression.. Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported.. This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child; Child Mortality; Child, Preschool; Communicable Diseases; Female; Humans; Infant; Male; Mass Drug Administration; Niger; Prevalence; Trachoma

We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.. In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.. A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.. Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Topics: Administration, Oral; Anti-Bacterial Agents; Azithromycin; Child Mortality; Child, Preschool; Communicable Disease Control; Communicable Diseases; Drug Resistance, Bacterial; Female; Humans; Infant; Infant Mortality; Malawi; Male; Mass Drug Administration; Niger; Public Health; Tanzania

Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth.. In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age.. We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49).. We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

Topics: Anti-Bacterial Agents; Azithromycin; Body Weight; Child Nutritional Physiological Phenomena; Child, Preschool; Cluster Analysis; Communicable Diseases; Female; Humans; Infant; Male; Niger; Nutritional Status; Thinness; Trachoma

To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae.. Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy.. Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05).. Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.

Topics: Adolescent; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chlamydia Infections; Chlamydophila pneumoniae; Communicable Diseases; Double-Blind Method; Drug Therapy, Combination; Erythromycin; Female; Humans; Infant; Male; Mycoplasma pneumoniae; Pneumonia, Bacterial; Pneumonia, Mycoplasma

Scrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar.. A 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly.. Next-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.

Topics: Aged; Animals; Azithromycin; Bacteremia; Bites and Stings; Communicable Diseases; Data Accuracy; Doxycycline; High-Throughput Nucleotide Sequencing; Humans; Male; Orientia tsutsugamushi; Scrub Typhus; Shock, Septic; Treatment Outcome; Trombiculidae

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child Mortality; Communicable Diseases; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Humans; Risk Assessment

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.

Topics: Artesunate; Azithromycin; Ceftriaxone; Child; Communicable Diseases; Critical Care; Dengue; Diagnosis, Differential; Doxycycline; Exanthema; Female; Fever; Geography; Humans; Intensive Care Units; Leptospirosis; Malaria; Male; Nervous System Diseases; Pregnancy; Shock, Hemorrhagic; Syndrome; Travel; Tropical Medicine; Typhoid Fever

Topics: Africa; Anti-Bacterial Agents; Azithromycin; Child Mortality; Child, Preschool; Communicable Diseases; Humans; Infant

A study published in 1998 linking MMR vaccine and autism was recently retracted by the Lancet because the data were falsified. The impressive reduction of invasive pneumococcal diseases with the 7-valent pneumococcal conjugate vaccine is due to a more than 90% reduction in rates of infections due to vaccinal serotypes at the expense of a slight increase in non-vaccinal serotypes. Genes encoding resistance factors to several antibiotic classes were detected in 30000-year-old samples. New Delhi metallo-beta-lactamase 1 was frequently detected in street water in New Dehli. Azithromycin decreased COPD exacerbations in a select group of patients with COPD at the cost of more frequent small decrements in hearing. Cranberry juice did not prevent recurrent urinary tract infections. Some patients with persistent symptoms after Lyme disease had higher levels of anti-Borrelia antibodies than cured patients.

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamase Inhibitors; beta-Lactamases; Communicable Disease Control; Communicable Diseases; Drug Resistance, Microbial; Epidemiology; Humans; Lyme Disease; Measles; Measles-Mumps-Rubella Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Pulmonary Disease, Chronic Obstructive; Serotyping; Vaccines, Conjugate

The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period.. We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection.. Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages.. Local elimination from a community is theoretically possible, even in the most severely infected communities. However, elimination from larger areas may require repeated biannual treatments and prevention of re-introduction from outside to treated areas.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Child; Child, Preschool; Chlamydia trachomatis; Communicable Diseases; Developing Countries; Drug Administration Schedule; Endemic Diseases; Ethiopia; Humans; Infant; Middle Aged; Models, Theoretical; Prevalence; Rural Population; Time Factors; Trachoma; Treatment Outcome