Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Clinical Uses of Inhaled Antifungals for Invasive Pulmonary Fungal Disease: Promises and Challenges.

The role of inhaled antifungals for prophylaxis and treatment of invasive fungal pneumonias remains undefined. Herein we summarize recent clinically relevant literature in high-risk groups such as neutropenic hematology patients, including those undergoing stem cell transplant, lung and other solid transplant recipients, and those with sequential mold lung infections secondary to viral pneumonias. Although there are several limitations of the available data, inhaled liposomal amphotericin B administered 12.5 mg twice weekly could be an alternative method of prophylaxis in neutropenic populations at high risk for invasive fungal pneumonia where systemic triazoles are not tolerated. In addition, inhaled amphotericin B has been commonly used as prophylaxis, pre-emptive, or targeted therapy for lung transplant recipients but is considered as a secondary alternative for other solid organ transplant recipients. Inhaled amphotericin B seems promising as prophylaxis in fungal pneumonias secondary to viral pneumonias, influenza, and SARS CoV-2. Data remain limited for inhaled amphotericin for adjunct treatment, but the utility is feasible.

The Management of Infectious Pulmonary Processes in the Emergency Department: Pneumonia.

Pneumonia is a common diagnosis encountered by emergency medicine providers. It is crucial that an accurate and timely diagnosis is established in order to appropriately manage each patient. Following the outbreak of SARS-CoV-2 in 2019, the frequency of patient visits to the emergency department for symptoms consistent with pneumonia have increased and overwhelmed virtually all hospital systems. The rapid identification of COVID-19 patients is imperative for patient care and to these hospital systems experiencing the pandemic. Community-acquired bacterial pneumonia continues to be prevalent and clinical decision-making tools are useful aids to assist the appropriate disposition of patients.

From the nose to the lungs: the intricate journey of airborne pathogens amid commensal bacteria.

The recent COVID-19 pandemic has dramatically brought the pitfalls of airborne pathogens to the attention of the scientific community. Not only viruses but also bacteria and fungi may exploit air transmission to colonize and infect potential hosts and be the cause of significant morbidity and mortality in susceptible populations. The efforts to decipher the mechanisms of pathogenicity of airborne microbes have brought to light the delicate equilibrium that governs the homeostasis of mucosal membranes. The microorganisms already thriving in the permissive environment of the respiratory tract represent a critical component of this equilibrium and a potent barrier to infection by means of direct competition with airborne pathogens or indirectly via modulation of the immune response. Moving down the respiratory tract, physicochemical and biological constraints promote site-specific expansion of microbes that engage in cross talk with the local immune system to maintain homeostasis and promote protection. In this review, we critically assess the site-specific microbial communities that an airborne pathogen encounters in its hypothetical travel along the respiratory tract and discuss the changes in the composition and function of the microbiome in airborne diseases by taking fungal and SARS-CoV-2 infections as examples. Finally, we discuss how technological and bioinformatics advancements may turn microbiome analysis into a valuable tool in the hands of clinicians to predict the risk of disease onset, the clinical course, and the response to treatment of individual patients in the direction of personalized medicine implementation.

Fungal infection mimicking COVID-19 infection - A case report.

For the last 2 years, one of the most frequent causes of respiratory failure is coronavirus disease 2019 (COVID-19). The symptoms are not specific. Imaging diagnostics, especially high-resolution computed tomography, is a diagnostic method widely used in the diagnosis of this disease. It is important to emphasize that not only SARS-CoV-2 infection may manifest as interstitial pneumonia. Other diseases such as other viral, fungal, atypical bacterial pneumonia, autoimmune process, and even cancer can also manifest as ground-glass opacities or consolidations in the imaging of the lungs. In this case report, we described a patient who manifested many symptoms that seemed to be COVID-19. However, all performed antigen and polymerase chain reaction tests were negative. The diagnostics must have been extended. Microbiological and mycological blood cultures and sputum cultures were performed. Blood cultures were negative but in sputum, Candida albicans and Candida glabrata were identified. Targeted therapy with fluconazole was implemented with a satisfactory result. The patient was discharged from the hospital in a good general condition with no complaints.

Study to assess aetiology, clinical and imaging characteristics of post Covid-19 pulmonary cavitation.

Objective: The aim of this study is to determine the aetiology and characteristics of pulmonary cavities that developed in patients recovering from COVID-19 infection. Materials and Methods: Between 1st May 2021 and 30st June 2021, we found 9 post COVID-19 patients who developed lung cavities on chest radiograph or CT during the follow-up period. These patients underwent routine blood examination, sputum examination and bronchoscopy to identify the aetiologies for the lung cavities. Results: The duration from the onset of COVID-19 symptoms to the detection of lung cavities ranged from 18 to 82 days. Out of 7 patients, 4 had recovered from severe COVID-19 disease, 2 from moderate and 1 from mild disease. After the diagnostic workup, 5 patients were found to have COVID-19 associated pulmonary aspergillosis (CAPA), 1 patient with mucormycosis and 1 patient with mycobacterium infection. Two patients with CAPA also had bacterial infection; sputum culture from both these patients grew Klebsiella pneumonia. Conclusion: Lung cavities can develop in patients recovering from COVID-19 pneumonia and fungal infection is the most common cause for such cavities.

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.