Voriconazole-induced arthritis, enthesitis and periostitis

Voriconazole is a fluoride-containing anti-fungal. Prolonged exposure can result in fluoride deposition within the bone extracellular matrix, resulting in periostitis and arthritis. We report a patient who developed widespread bony pain and polyarthralgia while on voriconazole therapy for COVID-19-associated pulmonary aspergillosis. No associated autoimmune rheumatic disease or alternative cause was noted. Blood investigations showed elevated total serum alkaline phosphatase, bone-specific ALP and fluoride levels, with normal serum voriconazole levels. A whole body nuclear bone scan showed multifocal periostitis. A diagnosis of voriconazole-induced periostitis and arthritis was made. Complete resolution of clinical symptoms with normalisation of the serum ALP occurred within four weeks of voriconazole cessation. While voriconazole-induced periostitis/arthritis is a recognised phenomenon in solid organ and haematopoietic stem cell transplant patients on long-term voriconazole, this case highlights the importance of having a high index of suspicion in other settings including CAPA. Clinical presentation can be mistaken for bony metastatic disease or other inflammatory arthritis.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Outcomes of a Pilot Contribution Database for the ICU Pharmacy Team at the University Hospitals of Leicester NHS Trust

Introduction It has long been felt that many contributions made by the ICU Pharmacy team, are not well showcased by the yearly regional network multi-speciality contributions audit. Themes specific to ICU are diluted amongst Trust and region wide data, and valuable learning for the multi-disciplinary team (MDT) is subsequently overlooked. Objective(s): The aims of this project were to: * Develop and pilot a MicrosoftTM Access © database for the ICU pharmacy team to record significant contributions. * Enable the production of reports to the ICU Quality & Safety board, to raise awareness, disseminate concerns, and influence future quality improvement projects. * Provide examples to contribute to the training of the whole MDT. * Generate evidence of team effectiveness and encourage further investment. * Provide team members with a means to recall contributions, for revalidation, appraisal, prescribing re-affirmation and framework mapping. Method(s): * A database was built with a user-friendly data-entry form to prevent overwriting. Fields were agreed with peers who would be using the database. * The team were invited to voluntarily enter their contributions which they thought added value and provided useful learning. * The pilot phase ceased with the emergence of the Omicron SARS-CoV-2 variant, due to staffing pressures and surge planning. Result(s): * Between 12/07/2021 and 25/11/2021, a total of 211 contributions were recorded. * Pharmacists entered 88.6% and a single technician entered 11.4% of these. * Independent Prescribing was utilised in 52.13% of contributions, and deprescribing in 25.12%. * Figure 1 demonstrates the contributions by drug group * The top 5 drugs associated with contributions were: ? Dalteparin ? Vancomycin ? Voriconazole ? Meropenem ? Co-trimoxazole * Treatment optimisation was an outcome for 76.3% of all contributions. Figure 2 stratifies these by type. Contributions. * Drug suitability was a cause for intervention in 12.8% of all contributions, encompassing allergies, contraindications, cautions and interactions and routes. * Medicines reconciliation accounted for 17.54% of all contributions, which almost half were Technician led. Admission was the most common stage to intervene (81.08%), followed by transcription. * Of all contributions, 37.91% were classified as patient safety incidents. Reassuringly 76.25% of these were prevented by the Pharmacy team. Themes have been extracted from these incidents and are presented in Table 1. Conclusion(s): PROTECTED-UK1 demonstrated the value pharmacists contribute to the quality and safety of patient care on ICU. Studies of similar quality and scale including Pharmacy Technicians are lacking, but even in this pilot study, it is evident how important their input is. Independent prescribing is a fundamental and well utilised part of our ICU Pharmacist skillset, supporting the GPICS2 recommendation that ICU pharmacists should be encouraged to become prescribers. Compiling a team interventions database is a useful tool to highlight local priority areas for guideline development;training;and ensuring that appropriate decision support is built into electronic prescribing systems. To improve the usefulness of the data, further stratification of contributions according to the Eadon Criteria3 may be worthwhile, to expand its use as a medication safety thermometer for ICU.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Correspondence to "Covid-19-associated Pulmonary Aspergillosis: A Case Series" by Sharma et al.

How to cite this article: Govindasaami V. Correspondence to "Covid-19-associated Pulmonary Aspergillosis: A Case Series" by Sharma et al. Indian J Crit Care Med 2023;27(5):370.

Assessing the safety profile of voriconazole use in suspected COVID-19-associated pulmonary aspergillosis-a two-centre observational study.

The decision to use voriconazole for suspected COVID-19-associated pulmonary aspergillosis (CAPA) is based on clinical judgement weighed against concerns about its potential toxicity. We assessed the safety profile of voriconazole for patients with suspected CAPA by conducting a retrospective study of patients across two intensive care units. We compared changes in any liver enzymes or bilirubin and any new or increasing corrected QT interval (QTc) prolongation following voriconazole use to patient baseline to indicate possible drug effect. In total, 48 patients with presumed CAPA treated with voriconazole were identified. Voriconazole therapy was administered for a median of 8 days (interquartile range [IQR] 5-22) and the median level was 1.86 mg/L (IQR 1.22-2.94). At baseline, 2% of patients had a hepatocellular injury profile, 54% had a cholestatic injury profile, and 21% had a mixed injury profile. There were no statistically significant changes in liver function tests over the first 7 days after voriconazole initiation. At day 28, there was a significant increase in alkaline phospahte only (81-122 U/L, P = 0.006), driven by changes in patients with baseline cholestatic injury. In contrast, patients with baseline hepatocellular or mixed injury had a significant decrease in alanine transaminase and aspartate transaminase. Baseline QTc was 437 ms and remained unchanged after 7 days of voriconazole therapy even after sensitivity analysis for concomitantly administered QT prolonging agents. Therefore, at the doses used in this study, we did not detect evidence of significant liver or cardiac toxicity related to voriconazole use. Such information can be used to assist clinicians in the decision to initiate such treatment.

Our study did not show significant voriconazole-related liver or cardiac side effects in a critically ill cohort of patients with suspected COVID-19-associated pulmonary aspergillosis. These findings may allay specific clinician concerns when commencing therapy for such patients.

[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Insights Into the Selective Imprinted Polymer of Voriconazole from Host-Guest Interaction Perspective

The incidence of fungal coinfections, such as Aspergillus spp., in patients with COVID-19 has been widely reported. Voriconazole is the first-line treatment for aspergillosis. A challenging sample preparation process is required to perform therapeutic drug monitoring of voriconazole. Recently, Molecularly Imprinted Polymers (MIP) have been shown to improve the separation selectivity for biological samples. Monomer selection in MIP is often performed by trial and error, without a design strategy. Therefore, this study aimed to construct a high-affinity MIP for voriconazole based on its interaction with functional monomers. All structures were optimized with B3LYP/6-311G++(d,p) and DFT-D3 dispersion correction method. Calculations of vacuum and solvated frequencies were carried out using a structure with maximum binding energy from molecular docking. The results showed that complex five was the most stable, exothermic, spontaneous, and enthalpy-driven among the complexes. In addition, there are nine intermolecular interactions and one moderate hydrogen bond in the QTAIM and NBO analysis, whereas hydrogen bonds, van der Waals interactions, and hydrophobic interactions were observed in the NCI-RDG analysis. The findings of this preliminary investigation showed that voriconazole possesses high stability when combined with functional monomers. It also provides information and assistance for further laboratory MIP synthesis.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Expect the Unexpected: Invasive Central Nervous System (Cns) Aspergillosis in Non-Neutropenic Patients - a Case Series of 15 Patients from India

Intro: Invasive aspergillosis of CNS is a severe form of aspergillosis & is associated with high mortality. Most of these cases are suspected & diagnosed in neutropenic patients. We hereby describe a series of 15 patients with CNS aspergillosis in non-neutropenic patients from a tertiary care hospital in India. Method(s): All patients with clinical & radiological features suggestive of CNS aspergillosis were screened for microbiological evidence of invasive aspergillosis, either by demonstration of hyphae by microscopy or histology, culture or galactomannan assay. Patients demographic details, clinical features, risk factors, diagnosis, management & outcome details were documented. Finding(s): A total of 15 patients were found to have CNS aspergillosis, 5 isolated CNS infections & 10 showing concomitant CNS & pulmonary aspergillosis in one between January 2021 to July 2022. The average age was 41.46+/-14.6y, with majority being male. Among the risk factors, most common ones were fungal sinusitis (46.6%), steroid use (40%), COVID-19 (33.3%). One patient had history of endoscopic sinus repair, another had h/o lung abscess. Most common symptoms of CNS aspergillosis were headache (73.3%), fever (60%), altered sensorium (53.3%) & seizures (47.6%). Radiologically, the common findings included ring enhancing lesion, s/o cerebral abscesses were observed in four patients. Direct microscopy s/o fungal hyphae were reported in 5 patients, with 4 culture positives. Average serum galactomannan was 1, while CSF galactomannan showed better sensitivity with mean CSF galactomannan being 2.53. Almost all patients were treated with Voriconazole based on weight, but showed high mortality of 60% even after initiation of therapy. Complete resolution were seen in only two patients, while 4 patients remaining static in improvement during 6 months follow up. Conclusion(s): Invasive CNS aspergillosis must be suspected even with nonneutropenic patients with newer emerging risk factors like steroid use, COVID-19 & h/o fungal sinusitis presenting with clinical & radiological manifestations.Copyright © 2023

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Invasive cerebral aspergillosis in non-neutropenic patients: A case series from Western India.

PURPOSE: Invasive cerebral aspergillosis (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021. METHODS: All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, histopathology and serum/CSF galactomannan. RESULTS: A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal brain abscess and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ Aspergillus antigen, Bio-Rad, France) with OD >1 and one patient had high serum galactomannan (OD >2). CSF culture grew Aspergillus species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement. CONCLUSION: Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.

Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis.

(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [Cmin] value of 3 mg/L normalized to the maintenance dose of 8 mg/kg/day) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated; (3) Results: Overall, 50 patients were included. The median average voriconazole Cmin was 2.47 (1.75-3.33) mg/L. The median (IQR) voriconazole concentration/dose ratio (C/D) was 0.29 (0.14-0.46). A CRP value > 11.46 mg/dL was associated with the achievement of voriconazole Cmin > 3 mg/L, with an AUC of 0.667 (95% CI 0.593-0.735; p < 0.001). A PCT value > 0.3 ng/mL was associated with the attainment of voriconazole Cmin > 3 mg/L (AUC 0.651; 95% CI 0.572-0.725; p = 0.0015). (4) Conclusions: Our findings suggest that in critically ill patients with CAPA, CRP and PCT values above the identified thresholds may cause the downregulation of voriconazole metabolism and favor voriconazole overexposure, leading to potentially toxic concentrations.

Contribution of voriconazole N-oxide plasma concentration measurements to voriconazole therapeutic drug monitoring in patients with invasive fungal infection.

BACKGROUND: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient's drug metabolism capacity. OBJECTIVES: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. PATIENTS AND METHODS: Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyse risk factors for the patient's concentration to be outside the therapeutic range. RESULTS: Based on 225 measurements, the median and interquartile range were 2.4 µg/ml (1.2; 4.2), 2.1 µg/ml (1.5; 3.0) and 1.0 (0.6; 1.9) for VRC, NOX and the MR, respectively. VRC Cmin <2 µg/ml were associated with a higher MR during the previous visit. MR values >1.15 and <0.48 were determined to be the best predictors for having a VRC Cmin lower than 2 µg/ml and above 5.5 µg/ml, respectively, at the next visit. CONCLUSIONS: Measurement of NOX resulted useful for TDM of patients treated with VRC. The MR using NOX informed interpretation and clinical decision-making and is very interesting for complex patients. VRC phenotyping based on the MR is now performed routinely in our institution. A dosing algorithm has been suggested from these results.

Azole resistance screening in Aspergillus species isolated from patients with COVID-associated pulmonary aspergillosis from Pakistan

Background: COVID-19 associated pulmonary aspergillosis (CAPA) complicates the course of critically ill COVID-19 patients. Delay in diagnosis and reports of azole resistance in CAPA patients lead to adverse outcome. We had previously reported CAPA rates of 21.7% from our center with high mortality. To detect azole resistance in Aspergillus species isolated from CAPA patients, we performed azole resistance screening. Material(s) and Method(s): Aspergillus species isolated from tracheal aspirates of CAPA patients admitted in Aga Khan University Hospital, Karachi, Pakistan during July 2020- January 2022, were screened for azole resistance as per CDC protocol. Minimum inhibitory concentration of screening positive strains were determined using YeastOne Sensititre plate. Result(s): 92 Aspergillus isolates were screened from 73 CAPA patients for azole resistance. Only 2 (2.17%) A. flavus isolates showed growth on voriconazole well, while other 90 (97%) isolates were screened negative for resistance (Table. 1). MICs of these two strains against posaconazole, voriconazole and itraconazole were 0.5 ug/mL, 1 ug/mL and 0.25ug/mL respectively. Table. 1: Aspergillus species distribution and growth on azole resistance screen agar Conclusion(s): We also did not find any azole resistance in this study. Periodic surveillance for the emergence of azole-resistant clinical isolates using molecular approaches is essential.

Recurrent Hydropneumothorax After COVID-19.

A 60-year-old male with a past medical history of heart failure with reduced ejection fraction, obstructive sleep apnea, atrial flutter, and hypertension initially presented to the emergency department with a chief complaint of shortness of breath. He was diagnosed with COVID-19-induced acute hypoxic respiratory failure. Before his presentation to the emergency department, he was treated with a brief course of hydroxychloroquine, azithromycin, and prednisone. His initial hospitalization was relatively uncomplicated. He then presented back to the emergency department approximately five months later with chief complaints of continued dyspnea and increased work of breathing. On this presentation, he was noted to have a right-sided pneumothorax with a moderate right-sided pleural effusion. The effusion was drained through CT (computed tomography)-guided catheter insertion. Pleural fluid culture and sensitivity were negative, and a cartridge-based nucleic acid amplification test (CBNAAT) was not performed. He was discharged a few days later to home. Over the next several weeks, the patient had recurrent admissions and chest tube placements for unresolving hydropneumothorax. He eventually had a right-sided posterolateral thoracotomy performed. The tissue sample from the thoracotomy was noted to have positive gram staining for fungal hyphae consistent with aspergillosis. This was initially considered a contaminant and not treated with antifungal medication. Unfortunately, after the thoracotomy, the patient continued to have complications including subcutaneous emphysema and recurring hydropneumothoraces. He was taken for another procedure after a repeat CT showed intercostal herniation of the pleura between the fifth and sixth ribs. The herniation was excised, and the pleura was repaired. This pleural tissue was then sent to pathology and noted to have non-caseating granulomas consistent with aspergillosis. At this time, the patient was started on voriconazole. After initiating this medication, the patient's last chest x-ray showed stable findings of his chronic disease process with no new or worsening hydropneumothorax.

Sphenoid Sinus Aspergilloma in an Immunocompetent and an Immunocompromised Patient: A Case Report.

Sellar, supra-sellar aspergilloma are rare differentials for a sellar mass. CNS aspergilloma occurs due to intracranial extension of invasive fungal sinusitis, and often first manifests with symptoms of headache and visual disturbance. This complication is much more common in immunocompromised patients, but proliferation of fungal pathogens and low index for suspicion has led to more severe breakthrough cases in the immunocompetent. If treated timely, these CNS lesions can have a relatively good prognosis. Conversely, delays in diagnosis can confer very high rates of mortality among patients with invasive fungal disease. Originally from India, in this case report, we describe two patients presenting with sellar, supra-sellar tumors, who eventually were diagnosed with confirmed cases of invasive intracranial aspergilloma. We describe the clinical presentation, imaging techniques, and treatment modalities for this relatively rare disease in both the immunocompromised and the immunocompetent.

COVID-19-associated Pulmonary Aspergillosis: A Case Series.

Background: With the development of coronavirus disease-2019 (COVID-19) pandemic, there is also increased risk of multiple secondary infections either disease- or drug-related. It includes many bacterial as well as invasive fungal infections. Patients and methods: There was suspicion of invasive pulmonary aspergillosis (IPA) infection in COVID-19 patients who were critically ill and had acute respiratory distress syndrome (ARDS). We did radiological evaluation and galactomannan assay in these patients. Result: We have diagnosed COVID-19-associated pulmonary aspergillosis (CAPA) in these patients and started antifungal treatment with voriconazole in all of these COVID-19 patients. Conclusion: It is very important to report such cases, so that healthcare professionals and authorities related to healthcare will be aware of and may also prepare for the increasing burden of this complication. We describe a case series of CAPA infection. How to cite this article: Sharma K, Kujur R, Sharma S, Kumar N, Ray MK. COVID-19-associated Pulmonary Aspergillosis: A Case Series. Indian J Crit Care Med 2022;26(9):1039-1041.