peramivir and Pneumonia--Viral

Human infections with avian influenza A (H5N1) are relatively rare but are associated with high mortality. As of July 5, 2010 there had been 500 cases and 296 fatalities. The influenza virus readily undergoes mutation and reassortment, and there are concerns that an H5N1 variant could be responsible for a future pandemic. The influenza neuraminidase inhibitors zanamivir and oseltamivir are approved for the treatment and prophylaxis of influenza. Oseltamivir is being used to treat H5N1 infections and the case has been made for a role for zanamivir; however, there are no case reports for the latter. Zanamivir is a potent inhibitor of H5N1, attains high lung concentrations immediately on administration, distributes into plasma at antiviral concentrations, has a low propensity for generating resistant virus, and retains activity against H275Y oseltamivir-resistant virus. There have been several reports of oseltamivir-resistant H5N1 arising during treatment with oseltamivir, and zanamivir retains effectiveness (in vitro or in vivo) against these isolates. Compassionate use of intravenous zanamivir for the treatment of seriously ill patients, including those with H275Y H1N1 infections, has also shown promising results. It is concluded that there is a role for zanamivir in treating H5N1 infections either as the approved, inhaled formulation in patients capable of using the Diskhaler, or as the intravenous formulation if compassionate use is warranted. The relatively small number of patients with these infections remains an obstacle to completion of clinical trials. Evidence is therefore likely to be based on carefully documented case reports, ideally in patients treated early in the course of the infection.

Topics: Acids, Carbocyclic; Antiviral Agents; Cyclopentanes; Disease Outbreaks; Drug Resistance, Viral; Guanidines; Humans; Immunocompromised Host; Influenza A Virus, H5N1 Subtype; Influenza, Human; Oseltamivir; Pneumonia, Viral; Pyrans; Severity of Illness Index; Sialic Acids; Zanamivir

The risk factors and the impact of NAI treatments in patients with severe influenza A-associated pneumonia remain unclear.. A multicenter, retrospective, observational study was conducted in Zhejiang, China during a severe influenza epidemic in August 2017-May 2018. Clinical records of patients (>14 y) hospitalized with laboratory-confirmed influenza A virus infection and who developed severe pneumonia were compared to those with mild-to-moderate pneumonia. Risk factors related to pneumonia severity and effects of NAI treatments (monotherapy and combination of peramivir and oseltamivir) were analyzed.. 202 patients with influenza A-associated severe pneumonia were enrolled, of whom 84 (41.6%) had died. Male gender (OR = 1.782; 95% CI: 1.089-2.917; P = 0.022), chronic pulmonary disease (OR = 2.581; 95% CI: 1.447-4.603; P = 0.001) and diabetes mellitus (OR = 2.042; 95% CI: 1.135-3.673; P = 0.017) were risk factors related to influenza A pneumonia severity. In cox proportional hazards model, severe pneumonia patients treated with double dose oseltamivir (300mg/d) had a better survival rate compared to those receiving a single dose (150 mg/d) (HR = 0.475; 95%CI: 0.254-0.887; P = 0.019). However, different doses of peramivir (300 mg/d vs. 600 mg/d) and combination therapy (oseltamivir-peramivir vs. monotherapy) showed no differences in 60-day mortality (P = 0.392 and P = 0.658, respectively).. Patients with male gender, chronic pulmonary disease, or diabetes mellitus were at high risk of developing severe pneumonia after influenza A infection. Double dose oseltamivir might be considered in treating influenza A-associated severe pneumonia.

Topics: Acids, Carbocyclic; Antiviral Agents; China; Cyclopentanes; Epidemics; Female; Guanidines; Humans; Influenza A virus; Influenza, Human; Male; Middle Aged; Neuraminidase; Oseltamivir; Pneumonia, Viral; Proportional Hazards Models; Retrospective Studies; Risk Factors

Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.

Topics: Acids, Carbocyclic; Aged; Betacoronavirus; China; Coronavirus Infections; COVID-19; Cyclopentanes; Extracorporeal Membrane Oxygenation; Female; Guanidines; Humans; Indoles; Lung; Moxifloxacin; Pandemics; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Virus Shedding

Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post-infection (dpi). The anti-HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti-HMGB1 mAb significantly improved survival rate whereas the anti-HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti-HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti-HMGB1 with conventional anti-influenza therapy might be useful against severe influenza virus infection.

Topics: Acids, Carbocyclic; Animals; Antibodies, Monoclonal; Antiviral Agents; Cyclopentanes; Cytokines; Drug Therapy, Combination; Guanidines; HMGB1 Protein; Inflammation; Injections, Intramuscular; Lung; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Orthomyxoviridae Infections; Pneumonia, Viral

To evaluate the difference of clinical efficacy of peramivir alone and peramivir combined with immunomodulators (either ribonucleic acid or thymopetidum) in the treatment of severe influenza A with primary viral pneumonia.. A retrospective analysis was applied to 45 patients who were diagnosed with severe influenza A with primary viral pneumonia in our hospital from December 2017 to March 2018. The cases were divided into three groups: the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group.. The duration of viral nucleic acid positivity in the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 6.13 ± 2.06, 6.53 ± 2.72, and 6.10 ± 1.37 days, respectively. The remission time of the clinical symptoms of the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 8.06 ± 2.73, 7.94 ± 2.89, and 7.67 ± 1.58 days, respectively. Comparisons between the peramivir group and the peramivir combined with ribonucleic acid group or the peramivir combined with thymopetidum group revealed no significant differences in the duration of virus nucleic acid positivity, remission time of clinical symptoms, time to fever alleviation, and time to cough alleviation.. There is no observed benefit in the addition of ribonucleic acid or thymopetidum when peramivir sodium chloride injection is used in the treatment of severe influenza A with primary viral pneumonia. This trial is registered with ChiCTR1800019417.

Topics: Acids, Carbocyclic; Adult; Aged; Antiviral Agents; Cyclopentanes; Drug Therapy, Combination; Female; Guanidines; Humans; Immunologic Factors; Influenza A virus; Influenza, Human; Male; Middle Aged; Pneumonia, Viral; Retrospective Studies; RNA; Young Adult

A 47-year-old man with a fever was highly suspected of having influenza A infection since his wife and son who lived with him had been diagnosed with influenza A. Although repeated rapid tests with a nasopharyngeal swab showed negative findings, the patient developed bilateral pneumonia and reverse transcription polymerase chain reaction (PCR) for A (H1N1) pdm09 virus in the bronchoalveolar lavage fluid was positive. We therefore diagnosed him with primary influenza pneumonia and initiated treatment with peramivir plus corticosteroids, which rapidly improved his condition. During the influenza season, sample collection from the lower airway and PCR should be considered for the definitive diagnosis of primary influenza viral pneumonia.

Topics: Acids, Carbocyclic; Adrenal Cortex Hormones; Bronchoalveolar Lavage Fluid; Cyclopentanes; Guanidines; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction

Topics: Acids, Carbocyclic; Antiviral Agents; Cyclopentanes; Drug Therapy, Combination; Guanidines; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Influenza A Virus, H1N1 Subtype; Influenza, Human; Pneumonia, Viral; Respiratory Insufficiency; RNA, Viral