ABSTRACT
Objectives: Mucormycosis is a rare invasive fungal infection with high lethality, affecting mainly patients with hematological neoplasia, decompensated diabetes, and covid-19 infection. The aim was to perform a cost-effectiveness analysis of liposomal Amphotericin B (standard treatment) versus isavuconazole for treating mucormycosis in the consolidation phase from the perspective of the Brazilian Unified Health System. Method(s): A decision tree model was built. The analysis considered the costs of the treatment over a six-month time horizon. This included hospitalization during the entire course of treatment and the expenditures related to dialysis, complication occurring in 5% (3%-6%) of cases treated with the Amphotericin B. Appointments with specialists were included in the isavuconazole arm, and amphotericin B was used if the patient failed to respond to isavuconazole. The utility of the patient with mucormycosis, cured and with renal failure was estimated. Uncertainties were assessed through probabilistic and deterministic sensitivity analyses. Result(s): The average cost of amphotericin B and isavuconazole arm was R$1.054.874,39 and R$522.344,05, respectively. The utility was 0.479 with amphotericin B and 0.480 with isavuconazole. The ICER was R$ -684,494,237 (dominant). In deterministic sensitivity analysis, the probability of dialysis was the variable with the greatest impact. In probabilistic analysis, the ICER is distributed in the right and left lower quadrant, the acceptability curve for all the scenarios analyzed is favorable for isavuconazole. The budget impact suggests a potential savings of between R$ 350 million and R$ 415 million over five years. Conclusion(s): The treatment of mucormycosis during the consolidation phase with isavuconazole represents a lower cost, besides the convenience of oral treatment and reduced incidence of severe adverse events, with mortality similar to the Amphotericin B arm. In Brazil, the formulation of posaconazole approved is inadequate for treating mucormycosis during the consolidation phase, therefore isavuconazole is the single oral drug available.Copyright © 2023
ABSTRACT
Invasive mould infections (IMIs), which are mostly caused by Aspergillus spp. and Mucormycetes, are opportunistic infections that impose a substantial threat to patients who are considered to be 'fragile'. There is no fixed definition for fragile patients; however, patients with cancer or acquired immunodeficiency syndrome (AIDS), patients who have undergone organ transplants, and patients being treated in the intensive care units (ICUs) were considered fragile. Management of IMIs in fragile patients is challenging, owing to their compromised immune status. The diagnostic challenges associated with IMIs due to insufficient sensitivity and specificity of the current diagnostic tests lead to delayed treatment. A widening demographic of at-risk patients and a broadening spectrum of pathogenic fungi have added to the challenges to ascertain a definite diagnosis. A recent surge of mucormycosis associated with SARS-CoV-2 infections and the resultant steroid usage has been reported. Liposomal amphotericin B (L-AmB) is the mainstay for treating mucormycosis while voriconazole has displaced amphotericin B as the mainstay for treating Aspergillus infection due to its better response, improved survival, and fewer severe side effects. The selection of antifungal treatment has to be subjected to more scrutiny in fragile patients owing to their comorbidities, organ impairment, and multiple ongoing treatment modalities. Isavuconazole has been documented to have a better safety profile, stable pharmacokinetics, fewer drug-drug interactions, and a broad spectrum of coverage. Isavuconazole has thus found its place in the recommendations and can be considered a suitable option for treating fragile patients with IMIs. In this review, the authors have critically appraised the challenges in ascertaining an accurate diagnosis and current management considerations and suggested an evidence-based approach to managing IMIs in fragile patients.
ABSTRACT
Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.
ABSTRACT
Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens - isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to explore in vitro antifungal susceptibilities against clinically important isolates of Aspergillus and Candida species (collected from intrapulmonary and sterile body areas, respectively). We applied the CLSI antifungal 2020 and the EUCAST antifungal 2020 guidelines. From 2017 to 2020, isolates of intrapulmonary Aspergillus fumigatus (n = 660), Aspergillus niger (n = 107), Aspergillus flavus (n = 96), Aspergillus terreus (n = 40), and Aspergillus nidulans species complex (n = 26) and sterile site-originated isolates of Candida albicans (n = 1,810), Candida glabrata (n = 894), Candida krusei (n = 120), Candida dubliniensis (n = 107), Candida lusitaniae (n = 82), Candida guilliermondii (n = 28), and Candida auris (n = 7) were enrolled in this study. Using the EUCAST 2020 breakpoints, it was demonstrated that amphotericin B and posaconazole displayed poor in vitro susceptibility rates against A. fumigatus isolates (<50% and 18.9%, respectively). In contrast, isavuconazole and itraconazole showed high in vitro potency against most Aspergillus isolates (>92%). Most intrapulmonary Aspergillus isolates exhibited MICs of ≤0.06 µg/mL to anidulafungin. Furthermore, intrapulmonary A. fumigatus isolates collected from Italy and the United Kingdom exhibited lower in vitro susceptibility to isavuconazole (72.2% and 69%, respectively) than those in the remaining ATLAS participant countries (>85%). Higher isavuconazole MIC90s against C. auris and C. guilliermondii (1 and 4 µg/mL, respectively) were observed compared to the other five Candida species. Despite the aforementioned MICs and susceptibilities against fungi, research needs to consider the pharmacokinetic (PK) profiles, pharmacodynamic (PD) parameters, and clinical treatment experience with antifungals against specific Aspergillus species. IMPORTANCE In addition to monitoring the antifungal susceptibilities of clinically important fungi, reviewing the PK/PD indices and the clinical therapy experience of antifungals under evaluation are important to guide an appropriate antifungal prescription. The efficacies of liposomal amphotericin B complex and anidulafungin for the treatment of pulmonary aspergillosis caused by different Aspergillus species need to be periodically evaluated in the future.
ABSTRACT
Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29-2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.
ABSTRACT
Mucormycosis is the most emerging angioinvasive fungal infection of filamentous fungi of the Zygomycetes class, which, when neglected, causes severe disseminated infection along with significant chances of morbidity and mortality. The diagnosis and treatment remain challenging for the doctors. It has been observed that people who have been suffering from different diseases, such as hematological malignancies and uncontrolled diabetes, or who have gone through different surgeries, such as hemato-poietic stem cell transplant, and solid transplantation, are the most affected ones. On the other hand, people who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically show the symptoms of mucormycosis after 1-2 weeks of successful recovery. Standard treatment of mu-cormycosis is traditionally considered an amphotericin B intravenous (IV) drug as initial therapy, alt-hough posaconazole and isavuconazole are also used. The core objective of the review is to typically focus on the area of the sudden cause of mucormycosis in the patients who have already recovered from SARS-CoV-2. Copyright © 2022 Bentham Science Publishers.
ABSTRACT
SESSION TITLE: Great Procedural Cases: Fire, Ice, Struts, Valves, and Glue SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: While rarely reported, there has been an increasing incidence of tracheobronchial mucormycosis in patients infected with COVID-19, especially when associated with uncontrolled diabetes mellitus. We describe a complex case of central airway obstruction due to mucormycosis that was managed with a custom 3D printed silicone Y-stent. CASE PRESENTATION: A 54-year-old woman with diabetes, prior COVID-19 infection, presented with dyspnea and cough. She underwent a CT chest which showed left lower lobe atelectasis and left main stem bronchus (LMSB) obstruction. Bronchoscopy showed a large exophytic mass extruding from the LMSB. There was necrosis leading to a fistula between the left and right mainstem bronchi distal to the carina. Pathology of the mass showed necrotic bronchial mucosa and cartilage with invasive mucormycosis. She underwent placement of a 10X40mm covered stent in LMSB. However, due to granulation tissue and recurrent mucus plugging, she needed a bronchoscopy every 3-4 weeks and multiple stent revisions. Despite these interventions, her respiratory symptoms did not change significantly. Ultimately, her airway was also complicated by tracheobronchomalacia (TBM) of the right main stem bronchus (RMSB). Subsequently a custom printed 3D silicone Y-stent from VisionAir was placed that allowed successful recanalization of LMSB and management of the TBM of RMSB simultaneously. The patient reported significant improvement in respiratory symptoms. She was maintained on Isavuconazole for mucormycosis suppression therapy DISCUSSION: Mucormycosis infections commonly occur in the pulmonary or rhino-cerebral region with high morbidity and mortality. Mucor can involve the major airways as well as rarely invade the tracheal cartilage leading to TBM. There is often granulation tissue, gray-white mucoid material, with edematous and necrotic airway. This can be associated with complex central airway obstruction. While the covered tracheobronchial stent (Bonastent) allowed us to recanalize LMSB, it was complicated by obstructive granulation tissue formation and mucous plugging requiring frequent stent revision to maintain stent patency. At the same time, the TBM in the right airway was contributing significantly to dyspnea and cough. While a standard silicon Y stent was considered for the management of bilateral mainstem bronchi disease, due to the significant distortion in airway anatomy this was not an ideal option. By using the VisionAir stent, we placed a custom stent that would best fit her airway anatomy. The patient had sustained improvement in her symptoms for several months following the procedure. CONCLUSIONS: This is the first case report of a custom designed and 3D printed stent for the treatment of benign central airway obstruction caused by tracheobronchial mucormycosis. Custom stents are a promising tool to individualize and tailor intervention for patients with complex airway anatomy. Reference #1: Tracheal Mucormycosis Pneumonia: A Rare Clinical Presentation. Satyawati Mohindra, Bhumika Gupta, Karan Gupta and Amanjit Bal. Respiratory Care November 2014, 59 (11) e178-e181 Reference #2: Keshishyan S, DeLorenzo L, Hammoud K, Avagyan A, Assallum H, Harris K. Infections causing central airway obstruction: role of bronchoscopy in diagnosis and management. J Thorac Dis. 2017;9(6):1707-1724. doi:10.21037/jtd.2017.06.31 Reference #3: Leon CA, Inaty H, Urbas A, Grafmeyer K, Machuzak M, Sethi S, Gildea T. Early outcomes with 3D printing and airway stents. CHEST 2019 annual meeting s. DISCLOSURES: No relevant relationships by Sisir Akkineni No relevant relationships by Kelly Daymude No relevant relationships by Wissam Jaber No relevant relationships by Abesh Niroula
ABSTRACT
SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: With the development of resistant organisms, additional therapies are needed to effectively treat patients with severe infections. The Seraph®-100 Microbind Affinity Blood Filter utilizes immobilized heparinized microbeads, acting similar as the human glycocalyx, to bind and remove these substrates. In vitro and pre-clinical studies have shown up to 99% clearance of Enterococcus faecalis exposed to the Seraph®-100 blood filter. This novel extracorporeal blood purification system could assist with infection source control and reduction of vasopressor requirements. CASE PRESENTATION: A 30-year-old male with no significant past medical history was admitted due to severe ARDS secondary to COVID-19 infection and required extracorporeal membrane oxygenation (ECMO) after an unsuccessful trial of conventional supportive therapies. The patient's hospital course was complicated by multiple infections, including bacteremia from methicillin susceptible Staphylococcus aureus, candidemia and Enterobacter ventilator associated pneumonia. These infections initially improved with use of appropriate intravenous antimicrobials. However, the patient experienced an acute hemodynamic decompensation requiring multiple vasoactive medications. He was empirically started on broad spectrum anti-microbials including meropenem, vancomycin, and isavuconazole. Blood cultures revealed Enterococcus faecalis, susceptible to broad-spectrum antibiotics. After 24 hours of broad-spectrum antimicrobials without improvements in vasopressor requirements, the Seraph-100® blood filter was used in-parallel with the ECMO circuit. Immediate improvement in vasopressors was noted with discontinuation of vasopressin and decrease in norepinephrine by 75%. The patient finished a 2-week course of intravenous ampicillin/sulbactam. His respiratory status subsequently improved and he was able to be removed from ECMO 24 days later. DISCUSSION: Initial studies have shown the Seraph-100 is capable of clearing the SARS-Cov-2 virus and use has been associated with decreased mortality in patients with SARS-Cov-2. The ability to remove additional pathogens including bacteria, fungi and viruses would aid in obtaining source control and augment the effects of intravenous antibiotics. This case not only illustrates the benefits with the use of the Seraph ®-100 blood filter along with broad spectrum antibiotics, but also the ability to use this extracorporeal blood purification system in-line with ECMO. CONCLUSIONS: With the emergence of multi-drug resistant pathogens, additional treatment options are urgently needed. The Seraph®-100 may be a useful adjunct to broad spectrum antimicrobials and may improve hemodynamics in patients with vasopressor-dependent septic shock. Further prospective studies are needed to assess clinical improvements with the use of the Seraph-100 Microbind blood filter in patients with bacteremia and those requiring ECMO. Reference #1: Olson SW, Oliver JD, Collen J, et al. Treatment for Severe Coronavirus Disease 2019 With the Seraph 100 Microbind Affinity Blood Filter. Critical Care Explor. 2020;2(8):e0180. Reference #2: Chitty, Stephen, Mobbs, Sarah, Chung, Kevin et al., for the PURIFY INVESTIGATORS. A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report. medRxiv 2021.04.20.21255810;doi: https://doi.org/10.1101/2021.04.20.21255810 Reference #3: Seffer, Malin-Theres, et al. "Heparin 2.0: a new approach to the infection crisis.” Blood Purification 50.1 (2021): 28-34. DISCLOSURES: No relevant relationships by Joshua Boster No relevant relationships by Henry Danchi Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No releva t relationships by Mai Nguyen No relevant relationships by Melissa Rosas No relevant relationships by Steven Stoffel No relevant relationships by Robert Walter
ABSTRACT
SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: PAP is a rare entity that can occur secondary to infection, malignancy, or trauma. Mucormycosis in the setting of Covid-19 pneumonia has been increasingly recognized but PAP has only recently been reported in this setting. CASE PRESENTATION: A 44 year-old man with type 2 diabetes, non-ischemic cardiomyopathy, hypothyroidism, and ulcerative colitis presented with dyspnea and cough in July 2021. He was diagnosed with Covid-19 pneumonia and initially treated with molnupiravir. Eight days later he presented to the emergency room with worsening dyspnea, hypoxemia and diabetic ketoacidosis. He required 3L of oxygen and was intubated for airway protection. CT chest revealed mild bilateral patchy opacities and dexamethasone was started. Unfortunately, persistent fevers and worsening respiratory status ensued and repeat chest CT on hospital day (HD) 8 showed a new large left upper lobe (LUL) cavitary lesion. Cultures ultimately grew Rhizopus microsporus and he was started on amphotericin then isavuconazole after acute kidney injury developed. Dexamethasone was discontinued and interval imaging after ten days showed dramatic growth of the cavitary lesion (9 x 6 x 3 cm) with new extension through the chest wall, infiltrating the intercostal spaces and pectoralis muscle. Due to ventilator dependency a tracheostomy was performed on HD 24. Despite anti-fungal therapy the cavitary lesion persisted, with evidence of osseous destruction of the third and fourth ribs, as well as new fluid collections within the cavity and hilar extension. On HD 46 he was transferred to our institution for Thoracic Surgery and Interventional Radiology (IR) evaluations. Percutaneous drain placement followed by pneumonectomy vs. staged cavernostomy was considered;however, on HD 50, the patient suddenly developed massive hemoptysis. CTA of the chest showed a 1.6 x 1.5 cm PAP with active hemorrhage from the LUL anterior segmental artery with dispersion into the cavity. Urgent coil and glue embolization was successfully performed by IR. Ultimately, thoracic surgical intervention was deemed too high risk and thus he was medically managed with a regimen of isavuconazole, amphotericin, and terbinafine. Hemoptysis did not recur and he was eventually discharged from the hospital and liberated from both mechanical ventilation and tracheostomy. Chest CT 6 months from the initial diagnosis has shown stable to mildly decreased size of the cavitary lesion. DISCUSSION: This is the first case to our knowledge of PAP as a complication of Covid-19 and Mucor superinfection in the United States. Five cases of this combination have been recently reported in other countries. Risk factors for Mucor infection after Covid appear to be uncontrolled diabetes, DKA, and steroid administration. CONCLUSIONS: A high index of suspicion should be maintained in patients with these risk factors, as PAP can present as massive hemoptysis and is often fatal. Reference #1: Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries [ 2022 Jan 25]. Lancet Microbe. 2022;10.1016/S2666-5247(21)00237-8. doi:10.1016/S2666-5247(21)00237-8 Reference #2: Pruthi H, Muthu V, Bhujade H, et al. Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature. Mycopathologia. 2022;187(1):31-37. doi:10.1007/s11046-021-00610-9 Reference #3: Coffey MJ, Fantone J 3rd, Stirling MC, Lynch JP 3rd. Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. Am Rev Respir Dis. 1992;145(6):1487-1490. doi:10.1164/ajrccm/145.6.1487 DISCLOSURES: No relevant relationships by Kevin Patel No relevant relationships by Clifford Sung
ABSTRACT
SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since the start of Covid-19 pandemic, several respiratory microorganisms have been identified that cause coinfection with Sars-Cov-2. Bacteria like Staphylococcus aureus and viruses like influenza are some of the identified pathogens. Rarely, fungal infections from Aspergillus are also being reported. CASE PRESENTATION: 59-year-old male with past medical history of hypertension and hyperlipidemia was admitted for shortness of breath and was found to be positive for Covid-19. He received Remdesivir, dexamethasone & tocilizumab. He required non-invasive ventilation via continuous positive airway pressure but continued to remain hypoxemic with elevated procalcitonin, he was treated with cefepime for bacterial pneumonia. Patient required emergent intubation and eventually underwent tracheostomy. He developed methicillin-resistant Staphylococcus aureus pneumonia for which he received vancomycin. He was eventually discharged to long term acute care facility. Patient was readmitted after 2 months due to worsening respiratory status. Computed Tomography Angiography of chest was negative for pulmonary embolism but showed pleural effusion. He underwent thoracentesis which showed exudative effusion with negative cultures. Echocardiogram showed right heart failure. Patient's symptoms were believed to be due to Covid-19 fibrosis. He required home oxygen and also received pulmonary rehabilitation. One year after the initial Covid-19 infection, he developed pulmonary hypertension and was referred for lung transplant consultation. However, he developed severe hemoptysis requiring intubation and vasopressors. Galactomannan was positive, Karius digital culture revealed Aspergillus Niger for which he received voriconazole. He was not deemed a suitable candidate for lobectomy. Patient developed arrhythmia and had prolonged QT interval so voriconazole was switched to Isavuconazole. He continued to have hemoptysis and his condition did not improve so family requested to transition care and patient passed away. DISCUSSION: Several studies have proven co-infection of Aspergillus with Covid-19. This case highlights Aspergillus infection approximately 1 year after initial Covid-19 infection. Sars-Cov-2 causes damage to airway lining which can result in Aspergillus invading tissues. IL-6 is increased in severe Covid-19 infection. Tocilizumab is an anti-IL-6 receptor antibody that has been approved for treatment of Covid-19 pneumonia. However, IL-6 provides immunity against Aspergillus so use of tocilizumab decreases protection against Aspergillosis which is usually the reason for co-infection. However, in this case patient developed fungal infection later during Covid-19 fibrosis stage. CONCLUSIONS: Recognizing fungal etiology early on is important in Covid-19 patients as mortality is high and appropriate intervention can reduce morbidity and mortality. Some patient may eventually require lung resection. Reference #1: Kakamad FH, Mahmood SO, Rahim HM, Abdulla BA, Abdullah HO, Othman S, Mohammed SH, Kakamad SH, Mustafa SM, Salih AM. Post covid-19 invasive pulmonary Aspergillosis: a case report. International journal of surgery case reports. 2021 May 1;82:105865. Reference #2: Nasrullah A, Javed A, Malik K. Coronavirus Disease-Associated Pulmonary Aspergillosis: A Devastating Complication of COVID-19. Cureus. 2021 Jan 30;13(1). Reference #3: Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-associated pulmonary aspergillosis (CAPA). Journal of Intensive Medicine. 2021 Oct 25;1(02):71-80. DISCLOSURES: No relevant relationships by Maria Haider Baig
ABSTRACT
CASE: A 31-year-old woman G4P2204 was admitted with respiratory failure. Her hemoglobin was 9.7 g/dl, D-dimer 1349 ng/mL feu, procalcitonin 0.44 ng/ mL, CRP 91.4 mg/L, normal white count and nasal RT-PCR positive for COVID-19. Chest x-ray showed bilateral patchy airspace opacities. She underwent emergent C-section, was intubated and placed on mechanical ventilation, received Remdesivir, dexamethasone, vancomycin and piperacillintazobactam. On day 11, she developed bilateral pneumothorces and had chest tubes placed. She had new elevation in white blood count (16,000/ul) and inflammatory markers. She was put on extracorporeal membrane oxygenation (ECMO). Computed Tomography ( CT) chest on day 15 showed large multiloculated cavity. She underwent bronchoscopy with bronchoalveolar lavage cultures positive for Mucorales. She had CT abdomen-pelvis, CT head and nasal endoscopy without evidence of invasive disease. She was started on amphotericin B and posaconazole. She had tracheostomy on day 21 and underwent successful ECMO weaning and decannulation on day 35. Chest tubes were removed. Amphotericin B was discontinued. She was discharged on nasal cannula and oral posaconazole and continued to improve. IMPACT/DISCUSSION: There are 6 other cases reported in literature with isolated pulmonary mucormycosis associated with SARS-CoV-2. All of these patients had clinical improvement before deteriorating again with SARS Cov-2 treatment. The timeline of new imaging findings like cavities, changing opacities, pleural effusions or bronchopleural fistula was usually 2 to 3 weeks from diagnosis of SARS-CoV-2 pneumonia. On analysis 5/7 of these patients were not diabetic, 6/7 received steroids, 3/7 received Tocilizumab and 4/7 received Remdesivir. 2 patients received surgical intervention with medical management although it did not change the outcome. Unfortunately despite aggressive medical and surgical treatment, there were poor outcomes. 4/7 patients died, 1/7 was permanently ventilator dependent and 2/7 survived. The diagnosis of isolated pulmonary mucormycosis is challenging. This might be secondary to hesitance of invasive diagnostic tests like bronchoscopy, lack of rapid diagnostic tests and fewer autopsies. Amphotericin B, posaconazole and isavuconazole remain the main treatment options along with surgical debridement of necrotic tissue. The pathology of mucormycosis in COVID-19 has been attributed to impaired T-cell function, impaired phagocytosis and more availability of fungal heme oxygenase which facilitates iron uptake for its metabolism. Glucocorticoids, IL-6 inhibitors and monoclonal antibodies further increase the risk of secondary infections. CONCLUSION: Mucormycosis is a lifethreatening disease with high morbidity and mortality. Based on our case and literature review, it is important to have high index of suspicion for pulmonary mucormycosis in patients who are recently treated with immunosuppressants for SARS-CoV-2 pneumonia and suddenly deteriorate after treatment.
ABSTRACT
Background and importance Isavuconazole is a new antifungal triazole authorised for invasive aspergillosis and mucormycosis. It is a therapeutic alternative to voriconazole and liposomal amphotericin B for invasive aspergillosis, and to liposomal amphotericin B in mucormycosis. Aim and objectives To analyse prescription characteristics of isavuconazole in patients with COVID-19 in an intensive care unit (ICU) as well as its effectiveness and safety. Material and methods A cross-sectional, observational study was conducted (June 2020-April 2021). Patients with COVID-19 in an ICU on treatment with isavuconazole were included. Electronic prescription program and clinical history were used to collect the following data: sex, age, comorbidities, coinfection with other pathogens in addition to SARS-CoV-2, type of therapy (empirical/targeted), duration and previous azole treatment (yes/no). Effectiveness was evaluated by symptoms resolution, reasons for treatment suspension and status (alive/death) 30 days after completion of treatment. Safety was assessed according to adverse events (AE). Results Thirty-three patients (54.5% men) with mean age of 61 (35-77) years were evaluated. Twenty-nine patients (87.9%) had comorbidities, the most frequent were: hypertension (19.1%), dyslipidaemia (12.8%), obesity (11.7%) and diabetes (8.5%). Thirty-two (96.9%) had coinfections, with a mean of 1.8 (SD 1.2) infections/patient. The most implicated pathogens were: Acinetobacter baumanii (18.8%), Candida albicans (11.6%) and Aspergillus fumigatus (8.7%). Twentythree patients (69.7%) received isavuconazole as empirical therapy and 10 (30.3%) as targeted. Mean duration of treatment was 12.3 (SD 7.5) days. Twenty-five (75.6%) patients had not previously received azole treatment, 7 (21.3%) had received voriconazole and 1 (3%) fluconazole. Symptoms resolution was observed in 12 (36.4%) cases. Seven patients (21.2%) discontinued treatment due to negative culture, 12 (36.4%) due to symptoms resolution and 14 (42.4%) due to death. At 30 days completion of treatment, 15 patients (45.5%) remained alive and 18 (54.5%) had died. AE were recorded in 6 cases (18.2%): liver disorders (n=4) and electrolytic alterations (n=2). Conclusion and relevance Most patients presented comorbidities and coinfections in addition to COVID-19. Effectiveness of isavuconazol was adequate in approximately one-third of patients, despite the high severity and clinical complexity. Approximately half the patients remained alive at 30 days following completion of treatment. Isavuconazol was well tolerated in most cases.
ABSTRACT
Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug-drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting.
ABSTRACT
The surge of COVID-19 associated Mucormycosis (CAM) in India during the second wave of COVID-19 led to lack of availability of amphotericin B(AmB). We retrospectively evaluated the outcome in 28 consecutive patients with CAM who received posaconazole (PCZ) or isavuconazole (ISVCZ) as sole or predominant therapy, based on factors like availability, affordability, site of infection or lack of treatment response. Therapeutic drug monitoring was used for PCZ in all cases & for ISVCZ in some cases. Higher trough levels were aimed to ensure therapeutic effect. Overall, 16 patients were cured, 5 patients improved, 6 patients died, of which 2 deaths were attributable to mucormycosis and 1 patient was lost to follow-up. The outcomes and survival were comparable to those reported in the literature. Although wider applicability of these results cannot be assumed, it leads to a speculation that treatment of mucormycosis with PCZ or ISVCZ, without AmB, is possible.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Mucormycosis , Antifungal Agents/therapeutic use , COVID-19/complications , Humans , Mucormycosis/drug therapy , Mucormycosis/microbiology , Nitriles , Pyridines , Retrospective Studies , TriazolesABSTRACT
Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens – isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines. © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Curvularia species are dematiaceous filamentous fungi that can cause a variety of infections in both immunocompetent and immunocompromised hosts. We present 2 cases of severely immunosuppressed patients with acute invasive fungal sinusitis due to Curvularia species. Both patients had a history of hematologic malignancy with refractory disease and prolonged neutropenia. They presented with facial and sinus pain, which prompted maxillofacial computed tomography that showed acute sinusitis. Subsequently, they underwent nasal endoscopy with a biopsy that revealed a definitive diagnosis of invasive fungal sinusitis. Dematiaceous fungi are responsible for most fungal sinusitis cases, with Curvularia being one of the most common species isolated. Generally, invasive fungal rhinosinusitis may follow a relatively innocuous and nonspecific course. In addition, fungal infections may complicate chronic allergic sinusitis. Computed tomography scan is the first imaging modality of choice, and magnetic resonance imaging has a role in prognostication in acute invasive fungal rhinosinusitis. Endoscopic sinus surgery with biopsy yields a definitive diagnosis and is therapeutic. Management typically includes a combination of surgery and antifungal agents. Severe neutropenia is a significant risk factor for infection and is associated with poor outcomes. Aggressive surgical debridement, combined with antifungal therapy, should be emphasized in leukemic patients despite their prolonged neutropenia and bleeding tendency.
ABSTRACT
Background. COVID-19 has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in case series of critically ill patients. However, the criteria for CAPA diagnosis has been inconsistent among most of the reports. Mexico has been widely affected by SARS-CoV-2. We present a series of CAPA cases at a teaching hospital in Mexico City. Methods. We performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from May 1st, 2020, to May 1st, 2021. Including only those with critical COVID-19 who required invasive mechanical ventilation (IMV). Patients with a diagnosis of CAPA were analyzed. We followed the 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika). Results. Among the 230 admitted patients who required IMV, we identified 49 (21.3%) cases of CAPA, 46 probable CAPA and 3 proven CAPA. Nineteen (38%) of those died in the hospital. The mean age was 64.5 ± 12.6 years and 11 were female. Proven CAPA was diagnosed with culture in three cases (one A. niger, one A. terreus and one A. fumigatus). Probable CAPA was diagnosed by a positive serum GP in 27 (55.1%) patients and by a positive bronchoalveolar lavage (BAL) GP in 29 (59.2%) cases. Seven patients had both serum and BAL positive GP. Forty-six (93.9%) patients received corticosteroids, and 22 (49.9%) were treated with tocilizumab before CAPA diagnosis. All but one received isavuconazole as CAPA treatment. We detected 35 (71.4%) patients who had a bacterial co-infection. Eighteen of those died (51.4%) compared to only one dead in the subgroup without coinfections (7.1%). The mean time from hospital admission to CAPA diagnosis was 6.2 days (SD 7.1) among those who survived compared to 13.2 (SD 6.3) days in those who died p< 0.01. Conclusion. CAPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality when it occurs with other bacterial coinfections and when it is diagnosed late from admission.
ABSTRACT
INTRODUCTION: Invasive aspergillosis is associated with high morbidity and mortality in immunocompromised patients. It is now increasingly reported in critically ill patients, including those with respiratory viral infections, such as influenza and COVID-19. Antifungal management is challenging due to diagnostic delay, adverse drug reactions, drug-drug interactions, narrow therapeutic window, and the emergence of resistance. Isavuconazole is the most recent FDA approved azole for the treatment of invasive aspergillosis, with data continuing to accumulate. AREAS COVERED: The authors review the safety and efficacy of isavuconazole in the management of invasive aspergillosis based on the currently available evidence. The authors also report on the structure, mechanism of action, pharmacokinetic properties, in vitro and in vivo studies as well as clinical safety and efficacy reports of isavuconazole since its FDA approval. EXPERT OPINION: Isavuconazole is non-inferior to voriconazole and is a safe, effective, and better tolerated option for the treatment of invasive aspergillosis. It offers several advantages over other antifungal agents, including having a better adverse event profile with respect to hepatotoxicity, neuro-visual toxicity, QTc prolongation, as well as a stable pharmacokinetic profile obviating the need for therapeutic drug monitoring. Further studies are needed to evaluate its performance in prophylaxis against invasive aspergillosis as well as in the treatment of aspergillosis in critically ill patients without underlying cancer or transplant.