A Review on Mucormycosis: Disease transmission, Risk factors, Management and Outcomes of Mucormycosis

To portray the study of disease transmission, the board and result of people with Mucormycosis; and to assess the danger factors related with mortality. We led a planned observational examination including continuous people with demonstrated Mucormycosis across 12 focuses from India. The segment profile, microbiology, inclining elements, the board and 90-day mortality were recorded; hazard factors for mortality were broke down. We included 465 patients. Rhino-orbital mucormycosis was the most well-known (315/465, 67.7%) show followed by aspiratory (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The inclining factors included diabetes mellitus (342/465, 73.5%), harm (42/465, 9.0%), relocate (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most well-known followed by Apophysomyces variabilis (23/290, 7.9%), and a few uncommon Mucorales. Careful treatment was acted in 62.2% (289/465) of the members. Amphotericin B was the essential treatment in 81.9% (381/465), and posaconazole was utilized as mix treatment in 53 (11.4%) people. Antifungal treatment was unseemly in 7.6% (30/394) of the people. The 90-day death rate was 52% (242/465). On multivariate examination, dispersed and rhino-orbital (with cerebral augmentation) mucormycosis, more limited span of manifestations, more limited length of antifungal treatment, and talent with amphotericin B deoxycholate (versus liposomal) were autonomous danger components of mortality. A joined clinical and careful the executives was related with a superior endurance. Diabetes mellitus was the prevailing inclining factor in all types of mucormycosis. Consolidated careful and clinical administration was related with better results. A few holes surfaced in the administration of mucormycosis. The more extraordinary Mucorales recognized in the investigation warrant further assessment.

Pharmacotherapy of Rhino-Orbital- Cerebral Mucormycosis

The aim of this study is Recently there is an alarming increase in the incidence of mucormycosis in patients diagnosed with Covid -19. In this short review, we will discuss the basic principles of mucormycosis treatment, antifungal agents used along with update on pharmacotherapeutic guidelines recommended for management of mucormycosis. Searching the Pubmed with the key words “mucormycosis and covid 19 ”, “ Treatment of mucormycosis”, “ antifungal used in Mucormycosis revealed many articles, and the relevant articles were screened. Mucormycosis is an aggressive disease which is difficult to diagnose in early stage with high morbidity and mortality. Multimodal therapeutic approach consisting of early diagnosis, urgent surgical and medical intervention and elimination of predisposing factors is key to successful management of this condition. First-line antifungal agent is high-dose liposomal amphotericin B although amphotericin B deoxycholate may be the viable option in resource limited settings.

Lymphocutaneous Sporotrichosis Refractory to First-Line Treatment

Sporotrichosis is a fungal infection endemic in Latin America and has been attributed to the thermodimorphic fungus of the genus Sporothrix. Transmission to humans occurs during a traumatic injury with soil or organic material; additionally, lesions caused by infected cats play an important role in the epidemiology of the disease. The classic treatment of sporotrichosis is performed with itraconazole or potassium iodide; second-line medications, such as amphotericin B and terbinafine, can alternatively be used in cases of first-line drug failure. In the present study, a patient with lymphocutaneous sporotrichosis in the right upper limb exhibited intolerance to itraconazole and potassium iodide, additionally during the period of use; these drugs did not control skin lesions. In this patient, amphotericin B deoxycholate and its liposomal version were used in this patient; and complete recovery of the lesions was observed.

Nghiên cứu thuần tập về độ an toàn của amphotericin B deoxycholate và các biện pháp dự phòng biến cố bất lợi tại Bệnh viện Phổi Trung ương

Mục tiêu: Nghiên cứu khảo sát biến cố bất lợi (AE) của amphotericin B deoxycholate (AmB-d) trên các bệnh nhân điều trị nấm xâm lấn. Đồng thời, nghiên cứu cũng đánh giá vai trò của việc truyền dung dịch NaCl 0,9% trong việc giảm độc tính trên thận và ảnh hưởng của thuốc trước truyền trong dự phòng phản ứng tiêm truyền do AmB-d. Đối tượng và phương pháp: Nghiên cứu thuần tập hồi cứu trên người bệnh được điều trị AmB-d từ ngày 01/01/2018 đến ngày 31/08/2020 tại Bệnh viện Phổi Trung ương. Kết quả: Trong tổng số 119 bệnh nhân, tỷ lệ AE trên lâm sàng và cận lâm sàng lần lượt là 24% và 90%. Trong đó, số lượng bệnh nhân gặp phản ứng liên quan tiêm truyền, hạ kali máu, và độc tính trên thận là 23 (19%), 79 (66%) và 48 (40%). Sử dụng dung dịch muối đẳng trương trước truyền với thể tích 1000ml hoặc 10 - 15ml/kg giúp giảm giá trị creatinin máu 5,24µmol (95%CI: -9,29 tới -1,19, p=0,011), trong khi sử dụng các thuốc dự phòng trước truyền giảm hơn 90% khả năng xảy ra phản ứng tiêm truyền (OR = 0,08, 95%CI: 0,03 - 0,28, p<0,001). Kết luận: Cần giám sát chặt chẽ các biến cố bất lợi khi sử dụng AmB-d. Bước đầu thấy việc sử dụng dung dịch muối đẳng trương và các thuốc trước truyền có thể làm giảm khả năng gặp độc tính trên thận và phản ứng liên quan đến tiêm truyền của AmB-d.

Population Pharmacokinetics and Pharmacodynamics of Itraconazole for Disseminated Infection Caused by Talaromyces marneffei

First-line treatment of talaromycosis with amphotericin B deoxycholate (DAmB) is labour intensive and toxic. Itraconazole is an appealing alternative antifungal agent. Pharmacokinetic data were obtained from 76 patients who were randomized to itraconazole in the Itraconazole versus Amphotericin B for Talaromycosis (IVAP) trial. Plasma levels of itraconazole and its active metabolite, hydroxyitraconazole, were analysed alongside longitudinal fungal colony forming unit counts in a population model. Itraconazole and hydroxyitraconazole pharmacokinetic variability was considerable, with area under the concentration-time curve over 24 hours (AUC 24 ) mean ± standard deviation 3.34 ± 4.31 mg*h/litre and 3.57 ± 4.46 mg*h/litre, respectively. Levels of both analytes were low; itraconazole minimum concentration (Cmin) 0.11 ± 0.16 mg/liter; hydroxyitraconazole Cmin 0.13 ± 0.17 mg/litre. The mean maximal rates of drug-induced killing were 0.206 and 0.208 log 10 CFU/mL/h, respectively. There were no associations between itraconazole Cmin:MIC and time to sterilisation of the bloodstream (HR 1.01, 95% CI 0.99 to 1.03, p=0.43), time to death (HR 0.99, 95% CI 0.96 to 1.02, p=0.77) or early fungicidal activity EFA (coefficient -0.004, 95% CI -0.010 to 0.002, p=0.18). Similarly, there was no relationship between AUC:MIC and time to sterilisation of the bloodstream (HR 1.00, 95% CI 0.99 to 1.00, p=0.50), time to death (HR 1.00, 95% CI 0.99 to 1.00, p=0.91) or EFA (coefficient -0.0001, 95% CI -0.0003 to 0.0001, p = 0.19). This study raises the possibility that the failure of itraconazole to satisfy non-inferiority criteria against DAmB for talaromycosis in the IVAP trial was a pharmacokinetic and pharmacodynamic failure.

Invasive fungal infections in kiney and liver transplant recipientes in a center in northeast Brazil

Objective: Describe the main invasive fungal infections (IFIs) after kidney and liver transplantation at a referral center, as well as their evolution, treatment, and clinical features. Material and Methods: This was a retrospective, observational, descriptive, case series study involving IFIs diagnosed between January 2012 and December 2019 in kidney and liver transplant recipients. Results: Among 769 kidney transplants, only 1 patient received the organ from a living donor and the other transplants were from deceased donors. 15 IFIs were diagnosed (7 histoplasmoses, 4 cryptococcoses, 3 candidemias, and 1 aspergillosis), while in 673 liver transplants, 8 IFIs were diagnosed (6 candidemias, 1 murcomycosis, and 1 cryptococcosis). Of the total 23 patients, 6 (26%) had infection diagnosed within 6 months after transplantation. The primary immunosuppressive regimen used was tacrolimus (82.6%), prednisone (82.6%), and mycophenolate (56.5%). Amphotericin B deoxycholate was the leading antifungal agent used for treatment, with nephrotoxicity in 80% of the cases. In the clinical follow-up, 14 patients progressed to cure (60.9%) and 9 to death (39.1%). A worsening of renal function was observed in most patients in the present study. Conclusion: Candidemia, histoplasmosis, and cryptococcosis were the most frequent IFIs, with the majority occurring later, 6 months after transplantation, and associated with high mortality.

Cost-effectiveness of amphotericin B deoxycholate versus itraconazole for induction therapy of talaromycosis in HIV-infected adults in Vietnam

Background Talaromycosis (penicilliosis) is an invasive fungal infection and a major cause of HIV-related deaths in Southeast Asia. Guidelines recommend induction therapy with amphotericin B deoxycholate, however treatment with itraconazole has fewer toxic effects, is easier to administer and is less expensive. Our recent randomized controlled trial in Vietnam found amphotericin B was superior to itraconazole with respect to six-month mortality. We undertook an economic evaluation alongside this trial to determine whether the more effective treatment is cost-effective. Methods Resource use, direct and indirect costs, health and quality of life outcomes (measured using quality-adjusted life-years; QALYs) were evaluated for 405 trial participants from 2012 to 2016. Both a Vietnamese health service and a broader societal costing perspective were considered. Mean costs and QALYs were combined to calculate the within-trial cost-effectiveness of amphotericin versus itraconazole from both perspectives. Results From a Vietnamese health service perspective, amphotericin increases costs but improves health outcomes compared to itraconazole, at a cost of $3,013/QALY gained. The probability that amphotericin is cost-effective at a conventional (WHO-CHOICE) threshold of value for money is 46%. From a societal perspective, amphotericin is cost-reducing and improves outcomes compared to itraconazole, and is likely to be a cost-effective strategy at any value for money threshold greater than $0. Conclusions Our analysis indicates that induction therapy with amphotericin is a cost-effective treatment strategy for HIV-infected adults diagnosed with talaromycosis in Vietnam. These results provide the evidence base for healthcare providers and policy makers to improve access to and use of amphotericin.

Ambulatory induction phase treatment of cryptococcal meningitis in HIV integrated primary care clinics, Yangon, Myanmar

Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

Efficacy of induction regimens for cryptococcal meningitis in HIV-infected adults: a systematic review and network meta-analysis

Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV–CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV–CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E−12, 95% CIs = 1.3E−41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV–CM patients.