amphotericin-b and Pneumonia--Viral

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

The combination of liposomes and aerosols has been utilized to directly target the lungs with chemotherapeutic agents that might not have been used because of low solubility or toxicity. There are a variety of antibacterials, antifungals, and antivirals that have good in vitro activity, but are not effective because of their systemic toxicity and/or poor penetration into the lungs. Incorporation of many lipophilic drugs into liposomes decreases their toxicity without affecting effectiveness, thus increasing the therapeutic index. We have focused on aerosol delivery of amphotericin B (ampB) for the treatment of pulmonary and systemic fungal diseases. We have tested a variety of ampB-lipid formulations for the optimal treatment regimen for Cryptococcus and Candida infections in mouse models. The AeroTech II nebulizer (MMADs of 1.8-2.2 microns) produced aerosols with the highest concentrations in the breathable range. Pharmacokinetic studies revealed that pulmonary drug was present for hours to weeks. AmBisome retained its anticryptococcal activity even when animals were challenged 14 days after aerosol treatment. Aerosols may also be effective in systemic diseases. In our Candida-mouse model, systemic candidiasis and mortality were reduced by aerosolized ampB-liposome treatment. The ability to utilize lipophilic drugs, to deliver high concentrations of drug directly to the site of infection, and to reduce toxicity makes aerosol liposomes an attractive, alternative route of administration.

Topics: Aerosols; Amphotericin B; Animals; Anti-Infective Agents; Antifungal Agents; Humans; Liposomes; Lung Diseases, Fungal; Mice; Pneumonia, Bacterial; Pneumonia, Viral

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Ganciclovir; Humans; Immunocompromised Host; Mycoses; Pneumonia; Pneumonia, Pneumocystis; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry.

Topics: Amino Acid Sequence; Amphotericin B; Antigens, Surface; Betacoronavirus; Cell Line; Coronavirus; Coronavirus Infections; COVID-19; Disease Susceptibility; Evolution, Molecular; GPI-Linked Proteins; Host-Pathogen Interactions; Humans; Pandemics; Pneumonia, Viral; Protein Sorting Signals; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization

A 28-year-old woman with acute lymphoblastic leukemia developed fever and unilateral pleural based pulmonary infiltrate during prolonged chemotherapy induced neutropenia. CT-guided lung biopsy confirmed the diagnosis of pulmonary mucormycosis and liposomal amphotericin B therapy was started. A few days after the initial symptoms, the patient developed convulsions and a brain abscess was detected in computerized tomography and magnetic resonance imaging. Fungal hyphae detected in histopathological examination of a brain biopsy had identical morphology with those seen in previous lung biopsies. The patient was treated with liposomal amphotericin B for five months and cytotoxic chemotherapy was successfully completed during antifungal therapy. Pulmonary infiltrates and the brain abscess resolved and the patient received an allogeneic bone marrow transplantation from a matched, unrelated donor. Antifungal therapy was continued for one additional month after bone marrow transplantation to prevent a relapse of invasive mucormycosis. Follow-up of the patient revealed no signs of relapse of invasive mucormycosis but two months after successful bone marrow transplantation the patient developed lethal cytomegalovirus pneumonitis which was confirmed by autopsy. No signs of mucormycosis were detected at post-mortem.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bone Marrow Transplantation; Brain Abscess; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Daunorubicin; Dexamethasone; Etoposide; Fatal Outcome; Female; Humans; Immunocompromised Host; Liposomes; Lung Diseases, Fungal; Mercaptopurine; Mitoxantrone; Mucormycosis; Pneumonia, Viral; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Transplantation, Homologous; Vincristine

Topics: Amphotericin B; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Drug Therapy, Combination; Humans; Infant, Newborn; Pneumonia; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Pneumonia, Viral

The first documented cure of cryptococcosis with cryptococcemia is reported. The patient had systemic lupus erythematosis and had received corticosteroids and immunosuppressive drugs for diffuse proliferative nephritis. She had additional poor prognostic factors including high serum cryptococcal antigen titer, low cerebrospinal leukocyte count, and absence of anticryptococcal antibody. Pulmonary tuberculosis was diagnosed concurrently and subsequently she developed disseminated herpes zoster. During amphotericin B therapy, renal function worsened. Cure of cryptococcosis with cryptococcemia was accomplished despite multiple concurrent infections and transient worsening of renal function.

Topics: Adult; Amphotericin B; Cryptococcosis; Female; Herpes Zoster; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Nephritis; Pneumonia, Viral; Tuberculosis, Pulmonary