zithromax and Influenza--Human

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Azithromycin; Betacoronavirus; Biomarkers; Cardiovascular Diseases; Chloroquine; Comorbidity; Coronavirus Infections; COVID-19; Cytokine Release Syndrome; Disseminated Intravascular Coagulation; Extracorporeal Membrane Oxygenation; Humans; Hydroxychloroquine; Immunosuppressive Agents; Influenza, Human; Lung; Myocardium; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Severe Acute Respiratory Syndrome; Troponin; Venous Thromboembolism

In chronic persistent asthma and severe acute exacerbations of bronchial asthma, infectious agents are the predominant triggers that drive disease and airway pathobiology. In acute exacerbations of bronchial asthma (AEBA) including near fatal and fatal asthma, viral agents, particularly human rhinovirus-C, respiratory syncytial virus and influenza A appear to be the more prevalent and recurring threats. Both viral, and to a lesser extent bacterial agents, can play a role, and co-infection may also be present and worsen prognosis in hospitalized patients, placing a portion at risk for critical asthma syndrome. During severe acute exacerbations, infectious agents must be treated empirically, but the initial treatment regimens can vary and viral coverage may also vary based on seasonality and patient age. Early treatment with ceftriaxone and azithromycin, along with oseltamivir in winter months, should be initiated with all cases of severe exacerbations where infection is suspected, and definitely in critical asthma syndrome until infection is excluded by appropriate diagnostic testing. In this manuscript we will outline the impact of the major viral agents on severe asthma including the data from the 2009 H1N1 influenza pandemic. The role of bacterial infections in acute exacerbations of asthma will also be reviewed as well as the benefit of empiric antibiotics and the role of macrolides in both acute and chronic asthma.

Topics: Animals; Asthma; Azithromycin; Bacterial Infections; Ceftriaxone; Coinfection; Critical Illness; Disease Progression; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Oseltamivir; Seasons; Syndrome

- Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking.. - A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0-10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data.. - Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: β -0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline -83.4% vs -59.5%), CXCL8/IL-8 (β -0.018, 95%CI-0.037,0.000, P = 0.056; -80.5% vs -58.0%), IL-17 (β -0.064, 95%CI-0.117,-0.012, P = 0.015; -74.0% vs -34.3%), CXCL9/MIG (β -0.010, 95%CI-0.020,0.000, P = 0.043; -71.3% vs -56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (β -0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin.. - We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study. [ClinicalTrials.gov NCT01779570].

Topics: Adult; Aged; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Cytokines; Female; Hospitalization; Humans; Influenza, Human; Longitudinal Studies; Macrolides; Male; Middle Aged; Oseltamivir; Plasma; Severity of Illness Index; Treatment Outcome; Viral Load

Macrolides have antibiotic and immunomodulatory activities, which may have a favorable effect on the clinical outcome of patients with infections, including influenza. This study aimed to evaluate the effects of combination therapy with an anti-influenza agent, oseltamivir, and a single-dose formulation of azithromycin (AZM), which has been used for influenza-related secondary pneumonia, on influenza patients. The primary endpoint was a change in the expression levels of inflammatory cytokines. Secondary endpoints were the time required for resolution of influenza-related symptoms, incidence of complications, and adverse reactions.. Patients with seasonal influenza were enrolled in this multicenter, open-label, randomized study. Patients were stratified according to the presence of a high risk factor and were randomized to receive combination therapy with oseltamivir plus an extended-release formulation of AZM (combo-group) or oseltamivir monotherapy (mono-group).. We enrolled 107 patients and randomized them into the mono-group (56 patients) or the combo-group (51 patients). All patients were diagnosed with influenza A infection, and none of the patients had comorbid pneumonia. Statistically significant differences were not observed in the expression levels of inflammatory cytokines and chemokines between the 2 groups. The maximum temperature in the combo-group was lower than that in the mono-group on day 3 through day 5 (p = 0.048), particularly on day 4 (p = 0.037).. To our knowledge, this is the first prospective, randomized, clinical trial of oseltamivir and AZM combination therapy for influenza. Although the difference in inflammatory cytokine expression level was not statistically significant, combination therapy showed an early resolution of some symptoms.. University hospital Medical Information Network (UMIN).. UMIN000005371.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Azithromycin; Cytokines; Drug Therapy, Combination; Female; Humans; Inflammation Mediators; Influenza, Human; Male; Middle Aged; Oseltamivir; Treatment Outcome; Young Adult

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

The potential antimicrobial and anti-inflammatory effectiveness of azithromycin against severe influenza is yet unclear. We retrospectively investigated the effect of intravenous azithromycin administration within 7 days of hospitalization in patients with influenza virus pneumonia and respiratory failure. Using Japan's national administrative database, we enrolled and classified 5066 patients with influenza virus pneumonia into severe, moderate, and mild groups based on their respiratory status within 7 days of hospitalization. The primary endpoints were total, 30-day, and 90-day mortality rates. The secondary endpoints were the duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability of the treatment weighting method with estimated propensity scores was used to minimize data collection bias. Use of intravenous azithromycin was proportional to the severity of respiratory failure (mild: 1.0%, moderate: 3.1%, severe: 14.8%). In the severe group, the 30-day mortality rate was significantly lower with azithromycin (26.49% vs. 36.65%,

Topics: Azithromycin; Hospitalization; Humans; Influenza, Human; Orthomyxoviridae; Pneumonia; Propensity Score; Respiratory Insufficiency; Retrospective Studies

BACKGROUND Legionella infection is a common cause of atypical pneumonia, known as Legionnaires' disease when infection extends to extrapulmonary involvement, which often leads to hospitalization. The triad of Legionella pneumonia, rhabdomyolysis, and renal failure displays a rare yet fatal complication without prompt management. CASE REPORT Our patient was a 62-year-old man with no significant medical history who developed Legionnaires' disease with severely elevated creatinine phosphokinase (CPK) of 9614 mcg/L, consistent with rhabdomyolysis. He experienced severe headache, anorexia, and hematuria, which prompted him to seek medical care. Pertinent social history included recent flooding in his neighborhood, which surrounded the outer perimeter of his home. His clinical manifestations and laboratory findings were consistent with Legionella infection, with concomitant acute kidney injury. A chest X-ray revealed hazy left perihilar opacities concerning for atypical pneumonia. Immediate interventions of hydration and antigen-directed azithromycin were initiated to prevent rapid decompensation. His clinical symptoms resolved without further complications, and he was not transferred to the Intensive Care Unit (ICU). CONCLUSIONS Legionella-induced rhabdomyolysis is an uncommon association that can lead to acute kidney failure and rapid clinical deterioration. Early and aggressive management with fluid repletion and appropriate antibiotics can improve clinical manifestations and hospital length of stay. Our patient's reduction in CPK levels and clinical improvement confirmed that extrapulmonary involvement in Legionella infection can lead to rhabdomyolysis. It is important for healthcare providers to recognize the clinical triad of Legionella pneumonia, rhabdomyolysis, and renal failure as prompt and timely management to reduce associated morbidity.

Topics: Acute Kidney Injury; Azithromycin; Humans; Influenza, Human; Legionnaires' Disease; Male; Middle Aged; Pneumonia, Mycoplasma; Rhabdomyolysis

Topics: Adenoviridae; Anti-Bacterial Agents; Antimicrobial Stewardship; Azithromycin; Cephalosporins; COVID-19; COVID-19 Drug Treatment; Fluoroquinolones; Humans; Hydroxychloroquine; Incidence; Influenza A virus; Influenza B virus; Influenza, Human; Italy; Macrolides; Pandemics; Penicillins; Physical Distancing; Prescription Drug Overuse; Quarantine; Respiratory Syncytial Viruses; Respiratory Tract Infections; SARS-CoV-2

The aim of this study was to describe the QTc prolongation and related adverse cardiac events during the administration of hydroxychloroquine (HCQ) and its combinations for the treatment of coronavirus disease 2019 (COVID-19). Hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who received HCQ and had initial and follow-up electrocardiograms performed between March 10 and May 30, 2020 were included. Critical QTc prolongation was detected in 12% of the patients. On multivariate analysis, diabetes mellitus (odds ratio 5.8, 95% confidence interval 1.11-30.32, p = 0.037) and the use of oseltamivir (odds ratio 5.3, 95% confidence interval 1.02-28, p = 0.047) were found to be associated with critical QTc prolongation.

Topics: Adult; Aged; Aged, 80 and over; Azithromycin; COVID-19 Drug Treatment; Electrocardiography; Female; Humans; Hydroxychloroquine; Influenza, Human; Long QT Syndrome; Male; Middle Aged; Oseltamivir; SARS-CoV-2

Using strategy of drug repurposing, antiviral agents against influenza A virus (IAV) and newly emerging SARS-coronavirus 2 (SARS-CoV-2, also as 2019-nCoV) could be quickly screened out.. A previously reported engineered replication-competent PR8 strain carrying luciferase reporter gene (IAV-luc) and multiple pseudotyped IAV and SARS-CoV-2 virus was used. To specifically evaluate the pH change of vesicles containing IAV, we constructed an A549 cell line with endosomal and lysosomal expression of pHluorin2.. Here, we identified azithromycin (AZ) as an effective inhibitor against multiple IAV and SARS-CoV-2 strains. We found that AZ treatment could potently inhibit IAV infection in vitro. Moreover, using pseudotyped virus model, AZ could also markedly block the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells. Mechanistic studies further revealed that such effect was independent of interferon signalling. AZ treatment neither impaired the binding and internalization of IAV virions, nor the viral replication, but rather inhibited the fusion between viral and vacuolar membranes. Using a NPC1-pHluorin2 reporter cell line, we confirmed that AZ treatment could alkalize the vesicles containing IAV virions, thereby preventing pH-dependent membrane fusion.. Overall, our findings demonstrate that AZ can exert broad-spectrum antiviral effects against IAV and SARS-CoV-2, and could be served as a potential clinical anti-SARS-CoV-2 drug in emergency as well as a promising lead compound for the development of next-generation anti-IAV drugs.

Topics: A549 Cells; Antiviral Agents; Azithromycin; Caco-2 Cells; COVID-19; COVID-19 Drug Treatment; HEK293 Cells; HeLa Cells; Humans; Influenza A virus; Influenza, Human; Interferons; SARS-CoV-2; Signal Transduction; Virus Internalization

Topics: Antiviral Agents; Azithromycin; Cohort Studies; Drug Therapy, Combination; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Length of Stay; Male; Middle Aged; Oseltamivir; Retrospective Studies; Treatment Outcome

More and more cases of human infections with avian influenza A H7N9 have been reported since it was first mentioned in 2013 in China, but concurrence of influenza A H7N9 with Mycoplasma pneumoniae, however, has never been described. Here, we reported the case of a woman co-infected by influenza A H7N9 and Mycoplasma pneumoniae, whose treatment process was a little bit longer and a little bit complicated as well.. Our patient was an 80-year-old Chinese woman who presented with fever, cough, chest tightness, and shortness of breath. A computed tomography scan showed obvious infiltrations at lower parts of both lungs. Arterial blood gas analysis confirmed a severe respiratory failure (type I). Her sputum and throat swabs were checked for nucleic acid of influenza A and the result was positive for influenza A H7N9. She was diagnosed as having severe influenza A H7N9 and acute respiratory distress syndrome, and was admitted to an intensive care unit. She was given comprehensive treatment, including oseltamivir, methylprednisolone, immunoglobulin, gastric protection, and noninvasive mechanical ventilation. Her condition improved 4 days later. However, some symptoms exacerbated again 2 days later with ground-glass changes appearing in upper area of right lung and the titer of antibody to Mycoplasma pneumoniae rising from 1:80 to 1:640. She was reasonably considered to be infected with Mycoplasma pneumoniae as well, and azithromycin and moxifloxacin were added to her treatment. Oseltamivir was discontinued because of three consecutive negative results of nucleic acid for influenza A H7N9, but anti-Mycoplasma treatment was continued. Although her symptoms and abnormal changes on computed tomography scan slowly went away, she finally recovered from the mixed infection after a total of 33 days of management.. In patients with confirmed influenza A H7N9 infection whose condition worsens again, especially with new infiltration or lung ground-glass infiltration, one should suspect infection by other pathogens such as Mycoplasma pneumoniae.

Topics: Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Coinfection; Female; Fluoroquinolones; Humans; Immunoglobulins; Influenza A Virus, H7N9 Subtype; Influenza, Human; Methylprednisolone; Moxifloxacin; Mycoplasma pneumoniae; Oseltamivir; Pneumonia, Mycoplasma

The combination of azithromycin, an immunomodulator, with oseltamivir was compared to oseltamivir monotherapy in a lethal BALB/c model of influenza A(H1N1)pdm09 infection. Groups of 14-16 mice received oral oseltamivir (10 mg/kg once daily for 5 days, starting at day 2 post-inoculation) alone or combined to azithromycin (a single 100 mg/kg dose, injected intraperitoneally at day 3 post-inoculation). Based on survival rates, lung viral titers, and pro-inflammatory cytokine levels, the combination therapy did not provide obvious additional clinical/virological benefits over oseltamivir monotherapy. Additional studies are still needed to better define the potential role of adjunctive immunomodulatory therapy for severe influenza infections.

Topics: Animals; Antiviral Agents; Azithromycin; Drug Therapy, Combination; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Injections, Intraperitoneal; Lung; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Oseltamivir; Viral Load

To assess provincial-level predictors among socioeconomic and influenza rate data for the use of different macrolide antimicrobials in Canada from 2000 to 2006.. Multivariable models were developed to describe macrolide defined daily doses per capita.. Use was highest during October to March for all macrolides. Investigated yearly and provincial patterns differed considerably among the macrolide agents. Associations with socioeconomic variables were similar between clarithromycin and erythromycin, while azithromycin consumption showed some differences in its association with these variables. Consistently, the rate of influenza was significantly associated with increased macrolide use. The influenza rate interacted with socioeconomic variables in some models; as the influenza rate increased, the greatest increase in demand for macrolides occurred in populations with high percentages of low-income individuals, high unemployment levels and low percentages of individuals with bachelor's degrees.. The impact of associations among macrolide consumption, influenza and socioeconomic factors may reflect inappropriate use of these agents to treat viral infections and/or prescribing for secondary infections, and knowledge of the virus versus bacteria problem and accessibility of healthcare. Further research surrounding differences in access to antimicrobial prescriptions and treatment options between advantaged and disadvantaged populations is suggested to further understand the dynamics of antimicrobial use in Canada.

Topics: Anti-Bacterial Agents; Azithromycin; Canada; Clarithromycin; Drug Utilization; Erythromycin; Health Knowledge, Attitudes, Practice; Humans; Influenza, Human; Macrolides; Risk Factors; Seasons; Socioeconomic Factors

Evaluation of: Morens DM, Taubenberger JK, Fauci AS: Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 198(7), 962-970 (2008). Secondary bacterial pneumonia is a common occurrence following lung influenza virus infection and leads to a significantly worse prognosis. This recent re-analysis of postmortem specimens and a vast number of reports from past influenza pandemics shows an extremely high frequency of lung colonization by bacterial species that are commonly found in the nasopharynx. This polymicrobial condition occurred in the preantibiotic era 1918-1919 influenza pandemic, but there is also evidence of bacterial co-infections in those outbreaks that occurred after antibiotic introduction. As such, antibiotic treatment should be included in any pandemic preparedness strategy. However, the choice of which antibiotic to use is important since some may even heighten morbidity and mortality.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Azithromycin; Cell Adhesion Molecules; Civil Defense; Disease Outbreaks; Epithelial Cells; Humans; Influenza, Human; Lung; Mice; Nasopharynx; Orthomyxoviridae; Pneumonia, Bacterial

The first case of 2009 pandemic influenza A (H1N1) virus infection in China was documented on May 10. Subsequently, persons with suspected cases of infection and contacts of those with suspected infection were tested. Persons in whom infection was confirmed were hospitalized and quarantined, and some of them were closely observed for the purpose of investigating the nature and duration of the disease.. During May and June 2009, we observed 426 persons infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in 61 hospitals in 20 provinces. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored, and 254 patients were treated with oseltamivir within 48 hours after the onset of disease.. The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours.. Surveillance of the 2009 H1N1 virus in China shows that the majority of those infected have a mild illness. The typical period during which the virus can be detected with the use of real-time RT-PCR is 6 days (whether or not fever is present). The duration of infection may be shortened if oseltamivir is administered.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antiviral Agents; Azithromycin; Child; Child, Preschool; China; Disease Outbreaks; Drug Therapy, Combination; Female; Humans; Incidence; Infant; Influenza A Virus, H1N1 Subtype; Influenza, Human; Logistic Models; Lymphopenia; Male; Middle Aged; Ofloxacin; Oseltamivir; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Time Factors; Virus Shedding; Young Adult