amphotericin-b and Influenza--Human

Acute respiratory distress syndrome is a common complication of severe viral pneumonia, such as influenza and COVID-19, that requires critical care including ventilatory support, use of corticosteroids and other adjunctive therapies to arrest the attendant massive airways inflammation. Although recommended for the treatment of viral pneumonia, steroid therapy appears to be a double-edged sword, predisposing patients to secondary bacterial and invasive fungal infections (IFIs) whereby impacting morbidity and mortality. Mucormycosis is a fungal emergency with a highly aggressive tendency for contiguous spread, associated with a poor prognosis if not promptly diagnosed and managed. Classically, uncontrolled diabetes mellitus (DM) and other immunosuppressive conditions including corticosteroid therapy are known risk factors for mucormycosis. Upon the background lung pathology, immune dysfunction and corticosteroid therapy, patients with severe viral pneumonia are likely to develop IFIs like aspergillosis and mucormycosis. Notably, the combination of steroid therapy and DM can augment immunosuppression and hyperglycaemia, increasing the risk of mucormycosis in a susceptible individual. Here, we report a case of sinonasal mucormycosis in a 44-year-old woman with hyperglycaemia secondary to poorly controlled diabetes following dexamethasone therapy on a background of influenza pneumonia and review 15 available literatures on reported cases of influenza and COVID-19 associated mucormycosis.

Topics: Adrenal Cortex Hormones; Adult; Amphotericin B; Antifungal Agents; COVID-19; Diabetes Complications; Female; Humans; Influenza, Human; Liposomes; Mucormycosis; Pneumonia, Viral; Triazoles

Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised patients. However, rarely, this infection can occur in normal hosts. This review of the literature identified 13 cases of IPA associated with influenza, of which 12 had influenza A and the type of influenza was not mentioned in the other case. Reported here is a case of IPA, which was associated with influenza B, in a 63-year-old immunocompetent woman. Her lungs showed gross invasion and she was treated with itraconazole and amphotericin B. She required mechanical ventilation for about 5 months but recovered completely. This is the first reported case of IPA associated with influenza B.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Female; Humans; Immunocompetence; Influenza B virus; Influenza, Human; Itraconazole; Lung Diseases, Fungal; Middle Aged

To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO). A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm. One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4-73.4). Ten (7%) patients had putative IPA and nine (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. The median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively. Immunosuppression and influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillus; Critical Illness; Echinocandins; Extracorporeal Membrane Oxygenation; Female; Galactose; Humans; Immunocompromised Host; Influenza, Human; Invasive Pulmonary Aspergillosis; Lipopeptides; Male; Mannans; Micafungin; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome; Voriconazole; Young Adult

The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon's protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.

Topics: Acetylcholine; Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Antigens, Differentiation; Biological Transport; Cell Fusion; Cell Line; Cell Membrane; Chlorocebus aethiops; COS Cells; HeLa Cells; Humans; Immunocompromised Host; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interferons; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Nystatin; Orthomyxoviridae Infections; RNA Interference; RNA, Small Interfering; Sodium; Tetraethylammonium; Virus Internalization; Virus Replication

We present a case of a 4.5-month-old boy from Turkey with hemophagocytic lymphohistiocytosis (HLH) associated with H1N1 virus and Leishmania spp. coinfection. Because visceral leishmaniasis can mimic hematologic disorders like HLH, it is important to rule out this clinical condition before starting immunosuppressive therapy. In our case, treatment with liposomal amphotericin B resulted in a dramatic resolution of clinical and laboratory abnormalities.

Topics: Amphotericin B; Antiprotozoal Agents; Child, Preschool; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Leishmaniasis, Visceral; Lymphohistiocytosis, Hemophagocytic; Male

In general, antibiotics are not rated as substances that inhibit or support influenza virus replication. We describe here the enhancing effect of the polyene antibiotic amphotericin B (AmB) on influenza virus growth in Vero cells. We show that isolation rates of influenza A and B viruses from clinical samples can be dramatically enhanced by adding AmB to the culture medium. We demonstrate that AmB promotes the viral uptake and endocytic processing of the virus particles. This effect is specific for Vero and human nasal epithelial cells and was not observed in Madin-Darby canine kidney cells. The effect of AmB was subtype specific and more prominent for human seasonal influenza strains but absent for H5N1 human viruses. The AmB-enhancing effect seemed to be solely due to the viral hemagglutinin function. Our results indicate that the use of AmB may facilitate influenza virus isolation and production in Vero cells.

Topics: Amphotericin B; Animals; Antifungal Agents; Cell Line; Chlorocebus aethiops; Dogs; Endocytosis; Epithelial Cells; Humans; Influenza A virus; Influenza B virus; Influenza, Human; Virus Replication

While invasive pulmonary aspergillosis usually occurs in immunocompromised hosts, it has been described after influenza virus infection in healthy individuals. The first case was a 76-year-old previously healthy woman admitted because of chest pain, cough, sputum, fever, and a chest radiograph abnormality. A transbronchial biopsy specimen showed fungal hyphae. Amphotericin B (AMPH) and Itraconazole (ITCZ) were given, and she improved gradually. A viral test showed a titre of 1/128 to influenza A. Case 2 was a 72-year-old previously healthy man admitted because of cough, fever, chest pain and a consolidation and cavitation on the chest radiograph. Antibiotics were ineffective. Cavitation with a halo sign appeared on the contralateral lung. Because his daughter was infected with Influenza B, we suspected he had been infected with IPA following influenza infection. AMPH and ITCZ and Micafungin sodium were given. His respiratory failure worsened, and on the tenth hospital day he required artificial ventilation; his condition improved gradually, (extubation after 40 days.) A viral test showed a titre of 1/128 to influenza B. IPA must be considered for the differential diagnosis of complications of influenza virus infection.

Topics: Aged; Alphainfluenzavirus; Amphotericin B; Antifungal Agents; Aspergillosis; Betainfluenzavirus; Diagnosis, Differential; Drug Therapy, Combination; Echinocandins; Female; Humans; Influenza, Human; Itraconazole; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Male; Micafungin; Peptides, Cyclic

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus niger; Bronchitis; Female; Humans; Influenza, Human; Interferon-gamma; Tracheitis

Invasive pulmonary aspergillosis can occur after viral influenza infection. It is described a previously healthy 58-year-old man with influenza virus infection who later suffered pulmonary aspergillosis. His response to amphotericin B was successful. The seven similar cases reported in the literature are revised and some common features established. Early antifungal therapy should be administered to any patient with previous flu illness presenting bilateral pulmonary infiltrates without response to antibiotics, if Aspergillus is isolated from the respiratory secretions.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Female; Humans; Influenza A virus; Influenza, Human; Lung Diseases, Fungal; Male; Middle Aged; Radiography, Thoracic

Topics: Amphotericin B; Ampicillin; Anti-Bacterial Agents; Bronchial Diseases; Humans; Influenza, Human; Kanamycin; Lung Diseases; Methicillin; Novobiocin; Oleandomycin; Tetracycline

Topics: Amphotericin B; Anti-Bacterial Agents; Cerebrospinal Fluid; Chloramphenicol; Humans; Influenza, Human; Leptospirosis; Meningitis; Meningitis, Pneumococcal; Meningitis, Viral; Mycoses; Neurosyphilis; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcus pneumoniae; Streptomycin; Tuberculosis; Tuberculosis, Meningeal