Maxillary mucormycosis and aspergillosis in post-COVID-19 patients in Mexico: A case series.

BACKGROUND: Fungal infections, during or as a consequence of SARS-CoV-2 infection, associated with uncontrolled diabetes mellitus and indiscriminate use of corticosteroids have been reported. In the jaw, mostly mucormycosis has been diagnosed in hospitals. METHODS: A retrospective, cross-sectional, descriptive study of the clinical, imaging, and histopathologic characteristics of maxillary invasive fungal infection in post-COVID-19 patients diagnosed in a private non-hospital oral pathology service in Mexico during 2020-2022 was conducted. RESULTS: We found 20 cases of maxillary invasive fungal infections in post-COVID-19 patients, 75% including a diagnosis of mucormycosis and 25% diagnosed as probable aspergillosis. The most common signs and symptoms were exposed necrotic bone followed by tooth mobility, discharge, and pain. On imaging, unilateral maxillary sinus involvement was observed in 6 cases (30%), and bilateral maxillary sinus involvement was observed in 3 cases (15%). CONCLUSIONS: It is essential to consider the association of osteonecrosis of the jaw in post-COVID-19 patients, with aspergillosis, not only mucormycosis, for early diagnosis and appropriate treatment.

Central nervous system Aspergillus quadrilineatus infection in a COVID-19 patient, a case report and literature review.

BACKGROUND: Viral pneumonia such as COVID-19-associated aspergillosis could increase susceptibility to fungal super-infections in critically ill patients. METHODS: Here we report a pediatric case of Aspergillus quadrilineatus cerebral infection in a recently diagnosed COVID-19-positive patient underlying acute lymphocytic leukemia. Morphological, molecular methods, and sequencing were used to identify this emerging species. RESULTS: Histopathological examination showed a granulomatous necrotic area containing dichotomously branching septate hyphae indicating a presumptive Aspergillus structure. The species-level identity of isolate growing on brain biopsy culture was confirmed by PCR sequencing of the ß-tubulin gene as A. quadrilineatus. Using the CLSI M38-A3 broth microdilution methodology, the in vitro antifungal susceptibility testing demonstrated 0.032 µg/mL MIC for posaconazole, caspofungin, and anidulafungin and 8 µg/mL against amphotericin B. A combination of intravenous liposomal amphotericin B and caspofungin therapy for 8 days did not improve the patient's condition. The patient gradually continued to deteriorate and expired. CONCLUSIONS: This is the first COVID-19-associated cerebral aspergillosis due to A. quadrilineatus in a pediatric patient with acute lymphocytic leukemia. However, comprehensive screening studies are highly recommended to evaluate its frequency and antifungal susceptibility profiles. Before being recommended as first-line therapy in high-risk patients, more antifungal susceptibility data are needed.

Invasive Aspergillosis in a Patient With Diabetes Mellitus as the Only Risk Factor: Case Report and Literature Review.

Infection by Aspergillus covers a broad clinical spectrum, including invasive pulmonary aspergillosis (IPA) and its disseminated extrapulmonary form, invasive aspergillosis (IA). It typically occurs in severely immunocompromised hosts, but it sometimes affects the immunocompetent population, especially patients with acute diseases being treated at the intensive care unit (ICU) and less often those with chronic conditions. In this article, we report the case of a 50-year-old male, with diabetes mellitus (DM) as the only risk factor, treated for IPA and IA with cardiac and central nervous system (CNS) involvement at a high complexity institution in Cali-Colombia. Clinical presentation and radiological findings are unspecific and require a high level of suspicion. To confirm the case, histological or cytological of the fungus is required; histopathological examination of lung tissue is the gold standard, but it is difficult to perform due to respiratory compromise and high risk of bleeding, so bronchoscopy and bronchoalveolar lavage (BAL) plays an essential role in the diagnostic process. A diagnostic algorithm that includes risk assessment, symptoms, imaging findings, and isolation in cultures is essential to allow the diagnosis and initiation of treatment promptly, which includes a combination of surgery and antifungal medications for long periods, even life-long treatment.

Invasive Aspergillus infection of middle ear in a patient treated with secukinumab, methotrexate, and corticosteroids for psoriasis and psoriatic arthritis.

Mucocutaneous mycotic infections are common complications in patients on IL-17 inhibitor therapy. We report a case of a 33-year-old male with severe psoriasis and psoriatic arthritis on secukinumab combined with methotrexate and prednisone with swelling, otorrhea, and pain of the right ear and external auditory canal. Due to progressive hypacusis, a surgical solution was chosen. Tissue samples taken during surgery revealed the presence of Aspergillus fumigatus. Aspergillosis should be suspected in prolonged otorrhea, especially in immunocompromised patients. Without intervention, the disease could be fatal.

Successful treatment of hepatic and mesh Aspergillosis in a neonate with giant omphalocele.

Aspergillosis is a rare and life-threatening fungal infection in immunocompetent children, particularly in infants. We present a case of invasive Aspergillosis (IA) that developed hepatic and mesh infection due to Aspergillus flavus following the rupture of a giant omphalocele. A male baby was born at 37 weeks of gestation with a giant omphalocele. No other congenital abnormalities were found. In the pediatric surgery operation room, the amniotic membrane seemed to be ruptured in some parts, which had been repaired within a few hours of birth. No further intervention to reduce the volume of visceral organs could be performed due to the tiny abdominal cavity. Postoperatively piperacillin-tazobactam and fluconazole were empirically initiated. Abdominal defects had been covered with polypropylene polylactic acid synthetic Mesh on postnatal day 11 to protect the organs and prevent abdominal infections. Fungal hepatic lesions were observed during surgery, and black necrotic lesions were also observed on the mesh on day 12. On the 16th postnatal day, Aspergillus flavus grew in the wound, graft, hepatic biopsy cultures. Serum galactomannan (GM) assay test was positive (GM:2.9), and voriconazole was initiated. All necrotic lesions resolved with liposomal amphotericin B (L-AmB) and voriconazole treatment, and antifungal therapy was discontinued after 134 days. Eye examination for the retinopathy didn't show any abnormalities. The patient was discharged with full recovery on day 155. In conclusion, IA is a rare and life-threatening infection in the neonatal period. To the best of our knowledge, this is the first case of hepatic and mesh infection caused by Aspergillus flavus that was successfully treated with voriconazole and l-AmB.

Fungal Necrotizing Scleritis After Intravitreal Injection Therapy.

PURPOSE: To report a case of infectious necrotizing scleritis secondary to Aspergillus terreus after intravitreal injection therapy. METHODS: This is a case report with literature review. RESULTS: A 98-year-old woman receiving intravitreal aflibercept injections for neovascular age-related macular degeneration in the left eye presented with severe pain, redness, and purulent discharge at the injection site. She was initially treated with topical fortified antibiotics, and clinical improvement was achieved, although microbial cultures showed negative results. Two months later, she presented with severe ocular pain and was diagnosed with anterior necrotizing scleritis. Scleral scrapings were collected for cultures, and intensive topical antibiotic therapy was reintroduced. Evaluation for autoimmune etiology and microbiological testing showed negative results. Because of the progression of the scleral necrotic area, empirical therapy with topical voriconazole was initiated, and surgical debridement was performed. Finally, the culture was positive for A. terreus. The modified therapy consisted of topical voriconazole and oral voriconazole for 3 months with an excellent clinical outcome. CONCLUSIONS: To our knowledge, this is the first case of fungal necrotizing scleritis secondary to intravitreal injection. Diagnosis was delayed due to its chronic clinical course and the slow fungal growth in culture media, but the combined medical and surgical approach resulted in a satisfactory outcome.

Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II-IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group.

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD.

Poor outcome and high prevalence of invasive fungal infections in patients with adult T-cell leukemia/lymphoma exposed to zidovudine and interferon alfa.

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.

Evaluating the Role of STAT3 in CD4+ T Cells in Susceptibility to Invasive Aspergillosis.

We aimed to determine whether T cell-specific STAT3 deletion influences the immune response to Aspergillus in the immunosuppressed context in CD4 Stat3-/- mice. Immunosuppressed and nonimmunosuppressed CD4 Stat3-/- mice and littermate Stat3flox/flox (Stat3fl/fl) mice were infected with Aspergillus fumigatus in an aerosol chamber, and the weight, activity, appearance, and respiratory rate of the mice were monitored daily for 21 days to evaluate their survival. Aspergillus infection was confirmed by lung fungal culture counts, histology, and a galactomannan test. Cytokines were measured at 3 days postinfection in bronchoalveolar lavage (BAL) fluid and serum. Immunosuppressed CD4 Stat3-/- mice began succumbing to infection by day 4, and by day 7, only 30% of mice survived. Immunosuppressed Stat3fl/fl mice started to succumb to the disease on day 5, and 40% of mice remained by day 7. The nonimmunosuppressed control Stat3fl/fl and CD4 Stat3-/- mice maintained their weight over the study period, without any evidence of infection by A. fumigatus by histology. In the BAL fluid, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interferon gamma (IFN-γ), IL-17A, and IL-22 levels were elevated in Stat3fl/fl immunosuppressed mice compared to immunosuppressed CD4 Stat3-/- mice at 3 days postinfection. STAT3 in CD4+ T cells modulates the production of cytokines in the IL-17 pathway in immunosuppressed mice. However, it has no meaningful effect on the clearance of Aspergillus or the concomitant increase in susceptibility to Aspergillus infection.

Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor.

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib.

Post-Tuberculosis Lung Disease: Clinical Review of an Under-Recognised Global Challenge.

An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD.

Endoscopic Findings of Fungal Ball in the Mucocele After Endonasal Transsphenoidal Surgery.

A 51-year-old woman with headache was referred to our hospital. She had a history of endonasal pituitary surgery 22 years prior and hypertension 10 years prior. The endonasal transsphenoidal pituitary approach was performed via microscopic transseptal approach. Nasal endoscopy revealed whitish cystic wall protruded from the right sphenoid sinus. Functional endoscopic sinus surgery was performed under general anesthesia. After incision of the right sphenoid ostium, yellowish mucoid discharge in the right sphenoid sinus was pushed out from the sphenoid sinus. Histopathology confirmed fungal ball in the sphenoid sinus, which is consistent with aspergillosis sinus. The presence of fungal ball and mucocele are rarely reported, but mucocele and fungal ball found after pituitary surgery are the first and therefore unique in this case.

Risk factors for the development of invasive aspergillosis after kidney transplantation: Systematic review and meta-analysis.

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.

High prevalence of triazole-resistant Aspergillus fumigatus sensu stricto in an Argentinean cohort of patients with cystic fibrosis.

BACKGROUND: Triazole resistance in Aspergillus fumigatus sensu stricto due to mutations in the cyp51A gene has been widely reported. Data from Argentina, and particularly from cystic fibrosis (CF) patients, are limited. OBJECTIVES: To investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus sensu stricto recovered from this population. METHODS: Ninety-three A. fumigatus isolates from 50 CF patients were retrospectively analysed for azole resistance using the standard microbroth dilution method according to CLSI M38-A2 guidelines. Sequencing analysis of the cyp51A gene and its promoter region was conducted in those isolates displaying high MIC values to itraconazole, voriconazole and/or posaconazole. RESULTS: Overall, 14% of isolates displayed high MIC values to at least one azole. Of them, 30.7% had the mutation TR34-L98H. No mutations in the cyp51A gene or its promoter were found in the remaining non-wild-type strains. Therefore, other mechanisms associated with azole resistance can be highly prevalent in these isolates. CONCLUSIONS: To the best of our knowledge, this is the first study in Latin America reporting azole-resistant A. fumigatus strains recovered from respiratory secretions of CF patients. Noteworthy, the prevalence of azole resistance in A. fumigatus sensu stricto in the studied Argentinean CF population is alarmingly high.

Benefits of risk-adapted and mould-specific antifungal prophylaxis in childhood leukaemia.

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.