Azithromycin Arm Research Articles

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies

Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250mg administered once daily 3 times a week for 2years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety. Eighty-nine patients received azithromycin (n=44) or placebo (n=45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P=.02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P=.03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P=.04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P=.004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.

Oral Azitromycin Prophylaxis, 250 Mg Once Daily Three-Times a Week, in Primary Antibody Deficiencies: A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial

Background. Lacking protective antibodies, patients with Primary Antibody Deficiencies (PAD) suffer from frequent respiratory infections leading chronic pulmonary damage. Macrolides prophylaxis has been proven effective in chronic respiratory diseases, including chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in PAD patients with chronic infection-related pulmonary diseases. Methods. A 3-year, randomized, double-blind, placebo-controlled trial was conducted in seven Italian immunology units. Eligible patients were aged 18-74 years, had a diagnosis of PAD with chronic infection-related pulmonary disease. Patients were randomly assigned (1:1) to receive azithromycin 250 mg once daily three-times a week for 2 years, or placebo. The primary outcome was the number of annual episodes of respiratory exacerbations. Secondary endpoints included time to the first exacerbation, additional doses of antibiotics to treat exacerbations, number of hospitalizations. Analysis was performed by modified intention to treat. This trial is registered with the Agenzia Italiana del Farmaco, Clinical Trials number: EUDRACT 2011-004351-39. Findings. Between November 2012 and December 2016, 90 patients were enrolled. We randomly assigned 89 patients to receive azithromycin (n=44) or placebo (n=45); 89 participants were comprised the modified intention-to-treat population. The number of exacerbations was 3·6 per patient-year (95%CI 2·5-4·7) in the azithromycin arm, and 5·2 (95%CI 4·1-6·4) in the placebo arm (p=0·02). In the azithromycin group the HR for having an acute exacerbation was 0·5 (95%CI 0·3-0·9, p=0·03) and the HR for hospitalization was 0.5 (95%CI 0·2-1·1) (p=0·04). The rate of additional antibiotic treatment per patient-year was 2·3 (95%CI 2·1-3·4) in the intervention and 3·6 (95%CI 2·9-4·3) in placebo groups (p=0·004). Four patients receiving placebo and none receiving azithromycin reported drug-related adverse events leading to treatment discontinuation. H.influenzae and S.pneumoniae were the prevalent isolates and they were non-susceptible to macrolides in 25% of patients of both arms. Interpretation. The study reached the main outcome centered in the reduction of exacerbation episodes per patient-year, leading to reduction of additional courses of antibiotics, and of risk of hospitalization. Adding azithromycin to the treatment regimen of PAD with respiratory exacerbation should be considered as a valuable option. Trial Registration Number: This trial is registered with the Agenzia Italiana del Farmaco, Clinical Trials number: EUDRACT 2011-004351-39. Funding. AIFA, Agenzia Italiana del Farmaco. Declaration of Interest: IQ and AP receipt of consultation fees and grants by Shire, CSL Behring, Octapharma and Kedrion; CA and AM receipt of consultation fees by Shire, Roche, CSL Behring, Octapharma, Novartis. CM, FP, FC, AP, MC, GL, VL, GF, BM, ST, DA, AS, GS, RMD and AV had none conflict of interest. Ethical Approval: The study protocol (EUDRACT: 2011-004351-39) was reviewed and approved by the Ethical Review Committee of Sapienza, University of Rome, Italy.

Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.

BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community’s gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1–60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson’s α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson’s index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical Trials RegistrationNCT02048007.

Relationship of Absolute Telomere Length With Quality of Life, Exacerbations, and Mortality in COPD

COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD. Using quantitative polymerase chain reaction, we measured the absolute telomere length (aTL) of DNA extracted from blood samples of 576 participants with moderate-to-severe COPD treated with either azithromycin or placebo for 12months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. All participants were followed for approximately 13months, during which time health status and exacerbations were carefully ascertained, and an additional 29months for mortality. The rates of exacerbation and mortality were determined by dividing the aTL into two groups using the median value as the cutoff. Participants with shorter telomere length had worse health status defined by higher St. George's Respiratory Questionnaire scores (β=-0.09, P= .034). In the placebo arm of the study, the rate of exacerbation (rate ratio, 1.50; 95%CI, 1.16-1.95; P= .002) and the risk of mortality (hazard ratio, 9.45; 95%CI, 2.85-31.36; P= .015) were significantly higher in the shorter telomere group than in the longer telomere group; these differences were not observed in the azithromycin arm (interaction P= .008 for exacerbation and interaction P=.017 for mortality) CONCLUSIONS: These data suggest that replicative senescence may help to predict poor outcomes in COPD. Shorter leukocyte telomere lengths may represent a clinically translatable biomarker for identifying individuals at increased risk of poor clinical outcomes in COPD.

Does azithromycin given to women in labour decrease ocular bacterial infection in neonates? A double-blind, randomized trial

BackgroundVertical transmission can result in neonatal infection and disease. Reducing the transmission of bacterial pathogens from mother to infant may be an effective means of preventing neonatal infection, including bacterial conjunctivitis.MethodsIn a double-blind, randomized trial, we assessed the effect of administering a single dose of oral azithromycin to women in labour on bacterial colonization of the neonate. A reduction in purulent neonatal conjunctivitis was a secondary objective of the trial. Ocular samples were collected from the lower fornix of infants presenting with clinical signs of purulent conjunctivitis during the first eight weeks of life. Incidence of purulent conjunctivitis was compared between trial arms. Bacterial infection was assessed using PCR and incidence of purulent conjunctivitis due to bacteria was also compared between arms.ResultsForty of 843 infants (4.7%) presented clinical signs of purulent conjunctivitis. No significant difference in incidence of purulent conjunctivitis was seen between azithromycin and placebo arms [4.3% (18/419) versus 5.2% (22/424), OR = 0.82, 95% CI (0.44,1.54), p = 0.628]. S. aureus was the most commonly identified pathogen, detected in 38% of cases. Incidence of purulent-conjunctivitis due to bacterial infection was lower in the azithromycin arm [1.2% (5/419) versus 3.8% (16/424), OR = 0.31, 95% CI (0.12–0.82), p = 0.025)]. The incidence of gram-positive bacteria was also lower in the azithromycin arm [1.0% (4/419) versus 3.3% (14/424), OR = 0.28, 95%CI (0.10–0.82), p = 0.029].ConclusionsOral azithromycin given to women during labour may have the potential to reduce the incidence of bacterial neonatal conjunctivitis.Trial registrationClinicalTrials.gov, identifier NCT01800942, registration date 26 Feb 2013.

006.4 Azithromycin versus doxycycline for urogenital chlamydia: a randomised clinical trial in females and males in youth correctional facilities

Background Urogenital Chlamydia trachomatis infection (“chlamydia”) remains highly prevalent and causes significant reproductive morbidity. Earlier randomised chlamydia treatment trials comparing azithromycin 1g versus a 7-day regimen of doxycycline 100mg twice daily reported high cure rates, but used less sensitive diagnostics and results may have been confounded by chlamydia re-exposure or doxycycline nonadherence. Recent studies have raised concern about azithromycin efficacy for chlamydia. Methods We conducted a randomised trial comparing azithromycin versus doxycycline for chlamydia in males and females in youth correctional facilities (YCFs) to evaluate for noninferiority of azithromycin compared to doxycycline. Treatment was directly observed and participants had no furloughs from the YCF throughout the study. The primary endpoint was treatment failure at 28 days after treatment initiation, determined by nucleic acid amplification test results, sexual history, and C. trachomatis OmpA genotyping. Results Of 567 participants enrolled, 284 were randomised to azithromycin and 283 to doxycycline. There were 155 participants in each treatment arm comprising the per protocol population: 65% male and 35% female. No treatment failures occurred in the doxycycline arm. In the azithromycin arm, five treatment failures occurred (3.2%; 95% CI: 0.4–7.4%): four were males (3.9%; 95% CI: 1.1–9.7%) and one female (1.9%; 95% CI: 0.0–10.1%). The observed failure rate difference in the treatments was 3.2%, with a 90% upper CI of 5.9%, exceeding the predetermined 5% cutoff for establishing azithromycin noninferiority. Conclusion Doxycycline had a 100% cure rate for chlamydia. Noninferiority of azithromycin to doxycycline was not established in this study, although azithromycin treatment failures occurred infrequently and the high azithromycin cure rate was consistent with earlier chlamydia treatment trials. Because of possible chlamydia treatment failures when azithromycin is used, further surveillance is needed and doxycycline might be considered for persons with suspected chlamydia treatment failure following azithromycin treatment. Disclosure of interest statement Nothing to Declare.

O19.1 Azithromycin and Doxycycline Resistance Profiles of Mycoplasma Genitalium and Association with Treatment Outcomes

BackgroundAntibiotic resistance profiles of recent Mycoplasma genitalium (MG) isolates have not been extensively evaluated nor correlated with treatment outcomes for NGU. Urine specimens from men with NGU enrolled in a...

A randomized controlled trial of azithromycin versus doxycycline/ciprofloxacin for the syndromic management of sexually transmitted infections in a resource-poor setting

A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment. Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C. trachomatis infection. These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment