zithromax and Respiratory-Syncytial-Virus-Infections

Despite a high disease burden, there is no effective treatment for respiratory syncytial virus (RSV) infection.. To determine whether administration of azithromycin (AZM) to children with RSV-induced respiratory failure is safe and to define the effect of AZM therapy on nasal matrix metalloproteinase 9 (MMP-9) levels.. This randomized, double-blind, placebo-controlled phase 2 trial was conducted at a single tertiary pediatric intensive care unit from February 2016 to February 2019. The study included children with RSV infection who were admitted to the pediatric intensive care unit and required respiratory support via positive pressure ventilation (invasive and noninvasive). A total of 147 children were screened; 90 were excluded for not meeting inclusion criteria, having an absent legal guardian, lacking pharmacy support, or having a language barrier and 9 declined participation, resulting in 48 patients enrolled in the study.. Receipt of standard dose AZM (10 mg/kg/d), high-dose AZM (20 mg/kg/d), or a matching placebo of normal saline intravenously for 3 days.. Nasal and endotracheal samples were collected at baseline as well as at 24 hours and 48 hours after start of treatment. The secondary outcome was to determine treatment effect on clinical outcome measures, including days of positive pressure ventilation and length of hospital stay.. A total of 48 patients were enrolled in the trial, with a median (range) age at randomization of 12 (1 to 125) months; 36 participants (75.0%) were younger than 2 years. Overall, 26 participants (54.2%) were boys, and 29 (60.4%) had a comorbidity. A total of 16 patients were randomized into each trial group (ie, placebo, standard-dose AZM, and high-dose AZM). Baseline demographic characteristics were comparable among the 3 groups. Both doses of AZM were safe, with no adverse events observed. No difference in nasal MMP-9 levels were observed between treatment groups. Among those who required mechanical ventilation and received high-dose AZM, endotracheal active and total MMP-9 levels were lower on day 3. Compared with baseline, active and total MMP-9 levels in endotracheal aspirates were 1.0 log lower in the high-dose AZM group (active MMP-9: 99.8% CI, -1.28 to -0.64; P < .001; total MMP-9: 99.8% CI, -1.37 to -0.57; P < .001). Patients who received high-dose AZM had fewer median (interquartile range) hospital days compared with those receiving the placebo (8 [6-14] days vs 11 [8-20] days; mean ratio estimate, 0.57; 95% CI, 0.38-0.87; P = .01).. In this phase 2 randomized clinical trial, both doses of AZM were safe. While nasal MMP-9 levels were unchanged among treatment groups, endotracheal MMP-9 levels were lower among those who received high-dose AZM. The positive secondary clinical outcome, while exploratory, provides insight for end points in a multicenter randomized trial.. ClinicalTrials.gov Identifier: NCT02707523.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Matrix Metalloproteinase 9; Positive-Pressure Respiration; Respiratory Insufficiency; Respiratory Syncytial Virus Infections; Viral Load

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis, Viral; Female; Humans; Infant; Infant, Newborn; Male; Microbiota; Moraxella; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory System

Respiratory syncytial virus (RSV) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. Because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing.. We sought to investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of postbronchiolitis recurrent wheezing.. We performed a randomized, double-masked, placebo-controlled proof-of-concept trial in 40 otherwise healthy infants hospitalized with RSV bronchiolitis who were treated with azithromycin or placebo for 14 days. IL-8 levels were measured in nasal lavage fluid and serum on randomization, day 8, and day 15 (nasal lavage only). The occurrence of wheezing episodes was assessed monthly over the ensuing 50 weeks.. Compared with placebo, azithromycin treatment did not reduce serum IL-8 levels at day 8 (P = .6) but resulted in a greater decrease in nasal lavage fluid IL-8 levels by day 15 (P = .03). Twenty-two percent of azithromycin-treated participants experienced at least 3 wheezing episodes compared with 50% of participants in the placebo group (P = .07). Azithromycin treatment resulted in prolonged time to the third wheezing episode (P = .048) and in fewer days with respiratory symptoms over the subsequent year in comparison with placebo (36.7 vs 70.1 days, P = .01).. In this proof-of-concept study azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels, prolonged the time to the third wheezing episode, and reduced overall respiratory morbidity over the subsequent year.

Topics: Azithromycin; Bronchiolitis, Viral; Disease Progression; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Nasal Lavage Fluid; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis, Viral; Female; Humans; Infant; Infant, Newborn; Male; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Viral Load

To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis (AB).. We performed a randomized, double-blinded, placebo-controlled trial in southern Brazil, from 2009 to 2011. Infants (<12 months of age) hospitalized with AB were recruited in 2 hospitals. Patients were randomized to receive either azithromycin or placebo, administered orally, for 7 days. At enrollment, clinical data were recorded and nasopharyngeal samples were collected for viral identification through immunofluorescence. Main outcomes were duration of oxygen requirement and length of hospitalization.. One hundred eighty-four patients were included in the study (azithromycin 88 subjects, placebo 96 subjects). Baseline clinical characteristics and viral identification were not different between the groups studied. A virus was detected in 112 (63%) patients, and of those, 92% were positive for respiratory syncytial virus. The use of azithromycin did not reduce the median number of days of either hospitalization (P = .28) or oxygen requirement (P = .47).. Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB, even when restricting the findings to those with positive respiratory syncytial virus samples. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance.

Topics: Acute Disease; Administration, Oral; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis, Viral; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Female; Hospitalization; Humans; Infant; Infant, Newborn; Influenza, Human; Kaplan-Meier Estimate; Length of Stay; Male; Oxygen Inhalation Therapy; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Treatment Outcome

Nearly half of all hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral) antibiotics. The present study was designed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of hospitalization in mild to moderate RSV LRTD.. Seventy-one patients < or =24 months of age with a virologically confirmed clinical diagnosis of RSV LRTD were randomized to azithromycin 10 mg/kg/day (n = 32) or placebo (n = 39) in a multicenter, randomized, double-blind, placebo-controlled equivalence trial during three RSV seasons (2002-2004 through 2005-2006). Primary endpoint was duration of hospitalization, secondary endpoints included duration of oxygen supplementation and nasogastric tube feeding, course of RSV symptom score, number of PICU referrals and number of patients who received additional antibiotic treatment. Data were analyzed according to the intention-to-treat principle using the Mann-Whitney U-test or chi2 test considering P < 0.05 as statistically significant.. Included patients were comparable with respect to baseline demographics, clinical characteristics, laboratory and roentgenologic investigations. The mean duration of hospitalization was not significantly different between patients treated with azithromycin or placebo (132.0 +/- 10.8 vs. 139.6 +/- 7.7 hr, P = 0.328). Azithromycin was not associated with a stronger resolution of clinical symptoms represented by the RSV symptom score. Four patients were treated with antibiotics after 72 hr, three of them were assigned to placebo (P = 0.406).. Infants and young children with RSV LRTD do not benefit from routine treatment with antibiotics (ISRCTN number 86554663).

Topics: Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Chi-Square Distribution; Double-Blind Method; Enteral Nutrition; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Intubation, Gastrointestinal; Length of Stay; Male; Oxygen; Patient Selection; Referral and Consultation; Research Design; Respiratory Syncytial Virus Infections; Severity of Illness Index; Statistics, Nonparametric; Therapeutic Equivalency

Respiratory syncytial virus (RSV) infection is an important cause of morbidity and mortality in vulnerable populations. Macrolides have received considerable attention for their anti-inflammatory actions beyond their antibacterial effect. We hypothesize that prophylactic azithromycin will be effective in reducing the severity of RSV infection in a mouse model.. Four groups of BALB/c mice were studied for 8 days: Control (C), RSV-infected (R), early prophylaxis with daily azithromycin from days 1 to 8, (E), and late prophylaxis with daily azithromycin from days 4 to 8 (L). Mice were infected with RSV on day 4, except for the control group. All groups were followed for a total of 8 days when bronchoalveolar lavage cell count and cytokines levels were measured. Mouse weight, histopathology, and mortality data were obtained.. Prophylactic azithromycin significantly attenuated post-viral weight loss between group R and both groups E and L (P = 0.0236, 0.0179, respectively). IL-6, IL-5, and Interferon-Gamma were significantly lower in group L (P = 0.0294, 0.0131, and 0.0056, respectively) compared with group R. The total cell count was significantly lower for group L as compared with group R (P < 0.05). Mortality was only observed in group R (8%). Lung histology in the prophylactic groups showed diminished inflammatory infiltrates and cellularity when compared with group R.. Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

Topics: Animals; Antibiotic Prophylaxis; Azithromycin; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Inflammation; Lung; Mice; Mice, Inbred BALB C; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses

Topics: Azithromycin; Humans; Infant; Infections; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Tract Infections

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

RSV is the most significant cause of serious lower respiratory tract infection in infants and young children worldwide. There is currently no vaccine for the virus, and antiviral therapy (e.g., ribavirin) has shown no efficacy against the disease. We reported that alternatively activated macrophages (AAMs) mediate resolution of RSV-induced pathology. AAM differentiation requires macrophage-derived IL-4 and -13, autocrine/paracrine signaling through the type I IL-4 receptor, and STAT6 activation. Based on these findings, we reasoned that it would be possible to intervene therapeutically in RSV disease by increasing AAM differentiation, thereby decreasing lung pathology. Mice treated with the IL-4/anti-IL-4 immune complexes, shown previously to sustain levels of circulating IL-4, increased the RSV-induced AAM markers arginase-1 and mannose receptor and decreased the lung pathology. Induction of PPARγ, shown to play a role in AAM development, by the PPARγ agonist rosiglitazone or treatment of mice with the macrolide antibiotic AZM, also reported to skew macrophage differentiation to an AAM phenotype, increased the AAM markers and mitigated RSV-induced lung pathology. Collectively, our data suggest that therapeutic manipulation of macrophage differentiation to enhance the AAM phenotype is a viable approach for ameliorating RSV-induced disease.

Topics: Animals; Antigen-Antibody Complex; Arachidonate 5-Lipoxygenase; Arginase; Azithromycin; Cell Differentiation; Drug Evaluation, Preclinical; Gene Expression Regulation; Interleukin-4; Lectins, C-Type; Lung; Macrophages; Mannose Receptor; Mannose-Binding Lectins; Mice; Mice, Inbred BALB C; PPAR gamma; Receptors, Cell Surface; Recombinant Proteins; Respiratory Syncytial Virus Infections; RNA, Messenger; Rosiglitazone; Sigmodontinae; Signal Transduction; STAT6 Transcription Factor; Thiazolidinediones