Fungal Superinfection Research Articles

Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU.

Rationale: Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19.Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications.Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male (n = 104; 72%), were overweight (n = 99; 68%), and had hypertension (n = 83; 57%) and diabetes (n = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half (n = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio, = 4.66; interquartile range, 1.98–7.34; P = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%).Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2–related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.

Presence of Incipient Fungal Infection in Atypical Squamous Lesions of the Lip.

Epidermal barrier disruption caused by atypical squamous proliferations of the lip (SOL) creates an ideal environment for fungal growth. Histologic features of SOL include parakeratosis overlying partial- or full-thickness keratinocyte atypia with or without invasion of the dermis, dermal solar elastosis, and scattered inflammatory cells which are predominantly lymphocytes. Histologic features of SOL with fungal superinfections overlap those seen in primary fungal cheilitis with reactive atypia, creating a diagnostic challenge. One-hundred seventy SOL cases were examined for the presence of fungal elements, and the histological features associated with superinfection were identified. Cases diagnosed as actinic cheilitis with fungal superinfection were carefully examined to rule out the possibility of misdiagnosed primary fungal cheilitis with reactive atypia. Histopathological characteristics commonly present with fungal hyphae included intraepidermal or intradermal neutrophils, bacterial colonies, and erosion or ulceration. Medical record review of those patients treated conservatively with topical antifungals revealed persistent clinical neoplasm and histological evidence of residual SOL on repeat biopsy. Thus, when biopsies exhibit histological overlap between these 2 entities, clinicians should keep a high index of suspicion for underlying SOL and carefully follow these patients if conservative antifungal therapy is initially trialed.

Corneal collagen cross-linking in mixed etiology keratitis treatment: a case of successful use

Acanthamoeba keratitis with bacterial, fungal superinfection or without it leads to development of an aggressive and long-standing corneal inflammation; up to now, the efficacy of its treatment stays doubtful and demands further investigation. For a long time, there were discussions on the possibility and expediency of corneal collagen cross-linking (PACK-CXL photo activated chromophore for keratitis) in patients with bacterial, fungal and Acanthamoeba keratitis. This article presents a clinical case of effective treatment of mixed etiology keratitis by multiple high fluence accelerated PACK-CXL in a patient with severe local toxico-allergic reaction.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease–associated pulmonary aspergillosis (CAPA) worldwide during March–August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.

Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study.

BackgroundBacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19.ObjectivesTo identify predictors of superinfections in COVID-19.MethodsProspective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections.ResultsOverall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445).ConclusionsThe risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Transcriptional Profiling of Immune and Inflammatory Responses in the Context of SARS-CoV-2 Fungal Superinfection in a Human Airway Epithelial Model.

An increasing amount of evidence indicates a relatively high prevalence of superinfections associated with coronavirus disease 2019 (COVID-19), including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection, we determine and compare the host transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus Aspergillus superinfection, using a model of reconstituted human airway epithelium. Our analyses reveal that both simple infection and superinfection induce strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and also the management of severe forms of aspergillosis in this specific context.

Immunological response to COVID-19 and its role as a predisposing factor in invasive aspergillosis.

The world is involved with a pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The clinical manifestations of reported COVID-19-associated pulmonary impairments range from asymptomatic infections to a pneumonia-induced acute respiratory distress syndrome that requires mechanical ventilation. Fungal superinfections complicating the clinical course remain underexplored. Angiotensin-converting enzyme 2, the receptor for COVID-19 that is mainly expressed in airway epithelia and lung parenchyma, is considered an important regulator of innate immunity. With regard to the viral-cell interaction, imbalanced immune regulation between protective and altered responses caused by the exacerbation of inflammatory responses should be considered a major contributor to secondary pulmonary aspergillosis. In addition, the complex inherited factors, age-related changes, and lifestyle may also affect immune responses. The complication and persistence of invasive aspergillosis have been well described in patients with severe influenza or COVID-19. However, there is a scarcity of information about the immunological mechanisms predisposing patients with COVID-19 to fungal co-infections. Therefore, this study was conducted to investigate the aforementioned domain.

Fungal superinfection in patients with COVID-19: Role of antifungal stewardship?

An area of great interest to the antimicrobial stewardship community is the presence of fungal superinfection, specifically invasive pulmonary aspergillosis (IPA), in patients with COVID-19. Classically a disease of the immunocompromised, isolated reports indicate a potentially increased risk for IPA in patients with COVID-19 who are nonimmunocompromised at baseline.1-4 During hospitalization, patients with COVID-19 have additional risk factors for IPA associated with interventions such as intubation and corticosteroid therapy.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID‐19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory‐confirmed COVID‐19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non‐SOT patients. We used a binomial generalized linear model (log‐binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non‐SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70‐1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non‐SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97‐1.85]). Death and organ support requirement were similar between SOT and non‐SOT critically ill patients with COVID‐19.

Bacterial and fungal superinfections in critically ill patients with COVID-19.

Bacterial and fungal superinfections in critically ill patients with COVID-19.

Treatments in Covid-19 patients with pre-existing metabolic dysfunction-associated fatty liver disease: A potential threat for drug-induced liver injury?

Obese patients who often present metabolic dysfunction-associated fatty liver disease (MAFLD) are at risk of severe presentation of coronavirus disease 2019 (COVID-19). These patients are more likely to be hospitalized and receive antiviral agents and other drugs required to treat acute respiratory distress syndrome and systemic inflammation, combat bacterial and fungal superinfections and reverse multi-organ failure. Among these pharmaceuticals, antiretrovirals such as lopinavir/ritonavir and remdesivir, antibiotics and antifungal agents can induce drug-induced liver injury (DILI), whose mechanisms are not always understood. In the present article, we hypothesize that obese COVID-19 patients with MAFLD might be at higher risk for DILI than non-infected healthy individuals or MAFLD patients. These patients present several concomitant factors, which individually can favour DILI: polypharmacy, systemic inflammation at risk of cytokine storm, fatty liver and sometimes nonalcoholic steatohepatitis (NASH) as well as insulin resistance and other diseases linked to obesity. Hence, in obese COVID-19 patients, some drugs might cause more severe (and/or more frequent) DILI, while others might trigger the transition of fatty liver to NASH, or worsen pre-existing steatosis, necroinflammation and fibrosis. We also present the main mechanisms whereby drugs can be more hepatotoxic in MAFLD including impaired activity of xenobiotic-metabolizing enzymes, mitochondrial dysfunction, altered lipid homeostasis and oxidative stress. Although comprehensive investigations are needed to confirm our hypothesis, we believe that the current epidemic of obesity and related metabolic diseases has extensively contributed to increase the number of cases of DILI in COVID-19 patients, which may have participated in presentation severity and death.

Coinfections in contact lens-associated mycotic keratitis with Pseudomonas or Acanthamoeba

Kontaktlinsenassoziierte Keratitiden werden immer häufiger. Die mykotische Keratitis ist ein relativ seltenes, aber sehr ernst zu nehmendes Krankheitsbild. Meist wird im Frühstadium eine falsche Diagnose gestellt und dadurch die adäquate Therapie verzögert. Bei der therapierefraktären kontaktlinsenassoziierten mykotischen Keratitis können nicht selten auch Koinfektionen oder Superinfektionen bestehen. Wir stellen 2 Patienten mit initial unklarer Keratitis vor, bei denen eine Mischinfektion der mykotischen Keratitis mit Pseudomonas aeruginosa bzw. Akanthamöben nachgewiesen werden konnte. In beiden Fällen war die zeitnahe perforierende Excimerlaser-Keratoplastik mit Einzelknüpfnähten und adäquater Lokaltherapie über 8 Wochen therapeutisch erfolgreich.

COVID-19 in Liver Transplant Recipients: An Initial Experience From the US Epicenter

COVID-19 in Liver Transplant Recipients: An Initial Experience From the US Epicenter

Chronic Liver Disease and COVID-19: Alcohol Use Disorder/Alcohol-Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis.

Chronic Liver Disease and COVID-19: Alcohol Use Disorder/Alcohol-Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis.

My Feet Are Killing Me: A Hiker’s Journey

My Feet Are Killing Me: A Hiker’s Journey

Maxillary sinusitis of odontogenic origin in relation to ectopic 2.8 associated with follicular dentigerous cyst: Combined transnasal and oral endoscopic approach, a case report

Purpose of the study: To describe the management of orosinusal pathology by combined transnasal endoscopy and oral combined. Methods: The 54-year-old patient underwent a dental and otolaryngological evaluation for left odontogenic maxillary sinusitis in relation to plausible dental follicular cyst of ectopic element 2.8. The symptoms reported at the time of access to the hospital were nasal obstruction and nocturnal rhonchopathy. To the ENT evaluation in videorinoscopy with rigid optics, complex deviation of the nasal septum was relevated with not any evident formations or pathological secretions. While on inspection of the oral cavity the mucous membranes appeared unscathed. Alveolus of 1.6 previosuly extracted was evident. The radiological examination, facial CT, revealed the left maxillary sinus almost completely occupied by a cystic appearance, with thin calcified walls and homogeneous content that has a dental element, probably the 2.8, which fenestrates the vestibular cortex of the lateral wall of the maxillary sinus. This lesion erodes the medial wall of the sinus, obliterating the ostio-meatal complex and imprinting the ipsilateral ethmoidal cells. Biohumoral tests showed normal coagulation parameters, indices of renal function, liver and ionemia. The patient under general anesthesia and oral intubation with a combined intervention of the left anterior FESS, intrasulcular flap from dental elements 2.7 to 2.3 with mesial releasing incision, moderate osteotomy, ectopic 2.8 extraction and enucleation of the cystic lesion with simultaneous closure of the orosinusal communication with advancement of the Bichat adipose bolla and closure by first intention. In the same session, the ENT moment is carried out trans nasally for total left uncinectomy, medium antrostomy with the union of the natural ostium and the accessory ostium. Bilateral lower turbinoplasty with bipolar forceps. The patient was then controlled after 15 days and six months, showing good healing and no signs of recurrence at the rhinoscopic check on the physical examination of the oral cavity. Results: based on the clinical and radiological aspect, the diagnosis of a follicular dentigerous cyst (WHO 2017) covered by a multi-layered non-keratinized paving epithelium, with moderate chronic inflammation, including gigantocellular and cholesteric crystals, is reached from the microbiological and histological examination. Necrotic amorphous material coexists including rare hyphae and fungal spores, with therefore mycotic and actinomycotic super infection. Conclusions: The combined oral and nasal intervention, allowed by the collaboration between the oral surgeon and ENT, has made it possible to shorten the healing time and to resolve the pathology without any sign of recurrence.

Fungal superinfection with herpes zoster of the tongue

Fungal superinfection with herpes zoster of the tongue

Management of adverse reactions to high-dose moxifloxacin used in multidrug-resistant tuberculosis treatment programmes.

The ‘Bangladesh regimen’, which is a 9-month multidrug-resistant tuberculosis (MDR-TB) treatment regimen that contains high-dose (maximum 800 mg once daily) gatifloxacin, clofazimine, ethambutol and pyrazinamide given throughout supplemented by high-dose isoniazid, prothionamide and kanamycin in the initial 4–6 months, has demonstrated safety and efficacy among second-line treatment-naïve patients.1 Gatifloxacin has been withdrawn from the market owing to reports of associated dysglycaemia. A prospective observational study of a modified Bangladesh regimen comprising standard-dose (400 mg once daily) moxifloxacin instead of high-dose gatifloxacin has demonstrated high treatment success rates among second-line treatment-naïve MDR-TB patients.2 STREAM Stage 1, a randomized controlled trial, has evaluated a modified Bangladesh regimen that contains high-dose (maximum 800 mg once daily) moxifloxacin instead of high-dose gatifloxacin in comparison with the longer 20-month fluoroquinolone-based MDR-TB treatment regimen recommended by the World Health Organization. Preliminary findings of the STREAM Stage 1 trial suggested that both regimens were similar by efficacy and the rates of severe adverse events, but with a non-significantly higher frequency of new-onset QT prolongation on electrocardiography.3 With publication of the final results, some national MDR-TB programmes may consider using shorter MDR-TB treatment regimens that contain high-dose rather than standard-dose moxifloxacin. We submit here some views that might help optimize management of the adverse reactions to high-dose moxifloxacin under programmatic settings. Standard-dose moxifloxacin can incur a wide range of adverse reactions (see Table 1, based on https://www.drugs.com/sfx/moxifloxacin-side-effects.html). Other important toxicities pertain to fungal superinfections and drug–drug interactions. Intuitively, as an extensive spectrum of adverse reactions to standard-dose moxifloxacin has been reported among non-TB patients treated for 1–2 weeks, one can reasonably predict similar, if not more frequent or severe, reactions to high-dose moxifloxacin among TB patients treated for 9 months. The current focus of many clinical trials on serious adverse drug reactions may not adequately address treatment tolerance, which substantially affects treatment adherence and outcomes in programmatic settings. Thus, many adverse drug reactions, which are frequently dose-dependent and aggravated by co-morbidities (especially those with organ dysfunction and ageing4, 5), are often insufficiently evaluated in clinical trial settings but highly pertinent at both patient care and programme implementation levels when a very large patient population is involved. The need of clinical vigilance and diligent monitoring for all potential toxicities associated with high-dose moxifloxacin is imperative, especially for cardiotoxicity, which necessitates periodic electrocardiographic assessment throughout the treatment for all patients, with possibly 24-h Holter monitoring for selected cases to comprehensively detect potentially dangerous arrhythmia. More research is apparently required to further inform clinical decision for the optimal management of moxifloxacin-induced cardiotoxicity, and to unravel a possible association between cardiac arrhythmia and disturbance of cardiac metabolism in the context of drug-induced cardiotoxicity.6 The use of a shorter MDR-TB treatment regimen containing high-dose moxifloxacin has potential programmatic advantages, especially pertaining to anticipated adherence and curtailment of drug resistance, but intensified clinical and related monitoring possibly has resource implication that might offset cost-effectiveness in programmatic settings. W.W.Y. was consultant to Otsuka Pharmaceutical Company until July 2016, and member of the Independent Data and Safety Monitoring Committee of the STREAM trial until September 2018.

Gastric Adenocarcinoma with Yolk Sac Differentiation, Fungal Super Infection and A Large Solitary Liver Metastasis - A Histologic Conundrum

Gastric Adenocarcinoma with Yolk Sac Differentiation, Fungal Super Infection and A Large Solitary Liver Metastasis - A Histologic Conundrum

Clinical and imagistic correlations in the inflammatory pathology of nasosinusal cavities

Abstract This article reviews the pathophysiology and the clinical and imaging diagnosis of rhinosinusal inflammations. Chronic sinusitis usually develops after an incompletely treated acute sinusitis. Complications occur through fungal superinfection, osteomyelitis, extension of the inflammatory process in the orbit or adjacent meningoencephalic structures. The imaging investigation is indicated as the symptoms get worse, for the elucidation of sinus contents, for establishing the therapeutic protocol, for identifying and finding solutions to solve nearby complications.