Targeted Delivery of Zinc Pyrithione to Skin Epithelia.

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving Malassezia yeast. Anti-fungal activity of ZnPT depends on the cutaneous availability of bioactive monomeric molecular species, occurring upon particle dissolution. The success of ZnPT as a topical therapeutic is underscored by the way it balances treatment efficacy with formulation safety. This review demonstrates how ZnPT achieves this balance, by integrating the current understanding of SD pathogenesis with an up-to-date analysis of ZnPT pharmacology, therapeutics and toxicology. ZnPT has anti-fungal activity with an average in vitro minimum inhibitory concentration of 10-15 ppm against the most abundant scalp skin Malassezia species (Malassezia globosa and Malassezia restrica). Efficacy is dependent on the targeted delivery of ZnPT to the skin sites where these yeasts reside, including the scalp surface and hair follicle infundibulum. Imaging and quantitative analysis tools have been fundamental for critically evaluating the therapeutic performance and safety of topical ZnPT formulations. Toxicologic investigations have focused on understanding the risk of local and systemic adverse effects following exposure from percutaneous penetration. Future research is expected to yield further advances in ZnPT formulations for SD and also include re-purposing towards a range of other dermatologic applications, which is likely to have significant clinical impact.

Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum.

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.

Association between voriconazole exposure and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

A rare entity to major outbreak: a case report on mucormycosis.

Mucormycosis is relatively uncommon, fulminant, progressive, life threatening fungal disease which is most often seen in debilitating patients with immunocompromised condition. Mucormycosis cases are seen in patients with the use of systemic steroids in the treatment of severely affected COVID-19 cases and also in the patients with uncontrolled diabetes which causes immunosuppression are being reported with mucormycosis. The main symptoms of this disease include pain on the temporal and the orbital region of the affected side which could be throbbing or lancinating type, mobility of the teeth, jaw pain and often swelling is present which could be extraoral and intraoral both or sometimes only intraorally. The diagnostic approach in such cases is done with the help of clinical diagnosis, histopathology and with advanced imaging like cone beam computed tomography, magnetic resonance imaging and computed tomography. We here used cone beam computed tomography imaging that revealed haziness in the sinuses and breach in cortical bone of the affected area which confirmed the diagnosis of mucormycosis. Early treatment planning like administration of antifungal drugs and surgical debridement will be life saving in such a deadly disease.

Acute graft-versus-host disease after liver transplantation in a close contact with COVID-19: A case report.

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.

Spontaneous Hemoptysis in a Patient With COVID-19.

CASE PRESENTATION: A 65-year-old man presented with shortness of breath, gradually worsening for the previous 2 weeks, associated with dry cough, sore throat, and diarrhea. He denied fever, chills, chest pain, abdominal pain, nausea, or vomiting. He did not have any sick contacts or travel history outside of Michigan. His medical history included hypertension, diabetes mellitus, chronic kidney disease, morbid obesity, paroxysmal atrial fibrillation, and tobacco use. He was taking amiodarone, carvedilol, furosemide, pregabalin, and insulin. The patient appeared to be in mild respiratory distress. He was afebrile and had saturation at 93% on 3 L of oxygen, heart rate of 105 beats/min, BP of 145/99 mm Hg, and respiratory rate of 18 breaths/min. On auscultation, there were crackles on bilateral lung bases and chronic bilateral leg swelling with hyperpigmented changes. His WBC count was 6.0 K/cumm (3.5 to 10.6 K/cumm) with absolute lymphocyte count 0.7 K/cumm (1.0 to 3.8 K/cumm); serum creatinine was 2.81 mg/dL (0.7 to 1.3 mg/dL). He had elevated inflammatory markers (serum ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, and creatinine phosphokinase). Chest radiography showed bilateral pulmonary opacities that were suggestive of multifocal pneumonia (Fig 1). Nasopharyngeal swab for SARS-CoV-2 was positive. Therapy was started with ceftriaxone, doxycycline, hydroxychloroquine, and methylprednisolone 1 mg/kg IV for 3 days. By day 3 of hospitalization, he required endotracheal intubation, vasopressor support, and continuous renal replacement. Blood cultures were negative; respiratory cultures revealed only normal oral flora, so antibiotic therapy was discontinued. On day 10, WBC count increased to 28 K/cumm, and chest radiography showed persistent bilateral opacities with left lower lobe consolidation. Repeat respiratory cultures grew Pseudomonas aeruginosa (Table 1). Antibiotic therapy with IV meropenem was started. His condition steadily improved; eventually by day 20, he was off vasopressors and was extubated. However, on day 23, he experienced significant hemoptysis that required reintubation and vasopressor support.

Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.

Susceptibility of severe COVID-19 patients to rhino-orbital mucormycosis fungal infection in different clinical manifestations.

PURPOSE: To present the different clinical manifestations of rhino-orbital mucormycosis (ROM) co-infection in severe COVID-19 patients. STUDY DESIGN: Prospective observational clinical study METHODS: Among 32,814 patients hospitalized with the diagnosis of COVID-19 between March 2020 and December 2020 in our center, eleven microbiologically confirmed ROM co-infection cases in severe COVID-19 patients were evaluated. RESULTS: There were nine men and two women with a mean age of 73.1 ± 7.7 years. Eight patients had uncontrolled type 2 diabetes with a mean diagnosis duration of 12.1 ± 4.4 years. All patients had COVID-19-associated acute respiratory distress syndrome and received corticosteroids. The mean time interval between COVID-19 diagnosis and ROM diagnosis was 14.4 ± 4.3 days. Seven patients (63.6%) had orbital apex syndrome, and four patients (36.4%) presented with orbital cellulitis. Endophthalmitis was detected in 54.5% of patients, and two of these patients developed retinoschisis. CT scan/MRI revealed sino-orbital involvement in all patients, and three of these had cerebral involvement at initial presentation. All patients received intravenous and retrobulbar liposomal amphotericin B and had undergone radical debridement of involved sinuses. Intravitreal liposomal amphotericin B injected in patients with endophthalmitis. Despite all measures, 63.6% of patients expired. CONCLUSIONS: Severe COVID-19 is associated with a significant incidence of ROM with higher mortality rates due to immune dysregulation and the widespread use of steroids. Physicians should be aware of the possibility of this infection in patients with COVID-19. An aggressive multidisciplinary approach can help to reduce mortality.

[Not all cases of groundglas opacity are COVID-19 - Pneumocystis-jirovecii-pneumonia as a differential diagnosis]. / Nicht alles Milchglas ist COVID-19 ­ Pneumocystis-jirovecii-Pneumonie als Differenzialdiagnose.

HISTORY AND CLINICAL FINDINGS: A 68-year-old male patient with psorias and a bullous pemphigoid as an underlying disease developed bilateral groundglass opacities on chest CT under longer-term, higher-dose immunosuppressive therapy with methylprednisolone with clinical symptoms of dry cough, progressive dyspnea and fever. DIAGNOSIS AND THERAPY: After the exclusion of COVID-19, Pneumocystis jirovecii pneumonia (PCP) was detected and a corresponding high-dose therapy with trimethoprim-sulfamethoxazole was initiated promptly. COURSE: Nonetheless, a complicated course with bacterial superinfection and pulmonary aspergillosis as well as ARDS developed. DISCUSSION AND CONCLUSION: In contrast to COVID-19, the typical course, diagnosis and therapy of Pneumocystitis jirovecii pneumonia are discussed. It is particularly emphasized that not all ground glass infiltrates in the CT chest image can be traced back to a COVID-19, even in a pandemic situation. Possible differential diagnoses should always be considered and taken into account in the diagnosis.

Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally, and the number is still increasing rapidly. Herein, we present four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all four patients (including a pregnant woman) recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy.