Pharmacokinetic/Pharmacodynamic Analysis the Probability of Target Attainment of Posaconazole against <i>Mucorales</i>Species in Patients with Mucormycosis

The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.

COVID-19-associated disseminated mucormycosis:An autopsy case report

BACKGROUND Reports of mucormycosis,an infectious disease that commonly affects immunocompromised individuals,have increased during the ongoing coronavirus disease 2019(COVID-19) pandemic.Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis.Our report documents a case of disseminated mucormycosis after COVID-19 infection.This is a rare pathological autopsy report on COVID-19-associated mucormycosis.CASE SUMMARY A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia.During treatment for acute respiratory distress syndrome,he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis.The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure,which led to death.An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection,which led to the necrosis of multiple infected organs.CONCLUSION Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

<i>Rhizopus oryzae</i>Retro-Orbital Abscess: Comparison of Spores and Hyphae Antifungal Susceptibility and Clinical Outcome

Rhizopus is fungus of the order Mucorales, responsible for invasive diseases called mucormycosis. The correct identification of these fungi is one of the main questions raised in the literature since the diagnosis is not simple, being the necessary detection in biopsies of infected tissues and isolation of the microorganism for identification by morphological and molecular methods. In vitro susceptibility testing results are not fully clear since there are reports showing that in vitro resistance does not always mean therapeutic failure. This paper describes a case of rhino-orbito-cerebral mucormycosis in a patient with alcoholic chronic pancreatitis and secondary mellitus diabetes involving microbiological diagnostic, antifungal susceptibility tests for conidia and hypha and clinical correlation. The causative agent was identified by morphological characteristics and DNA sequencing. Minimal Inhibitory Concentration (MIC) for amphotericin B (AMB), itraconazole (ITZ) and terbinafine (TERB) was determined by broth microdilution method. Standardization of the dynamic growth evaluation patterns using the automated system BCT (BioCell-Tracer?) was obtained allowing to determining hyphae growth control and evaluating the effect of different concentrations of amphotericin B, itraconazole and terbinafine directly on growing hyphae. The fractional inhibitory concentration (FIC) for the combination of the two antifungals that the patient received at the same time, terbinafine and itraconazole, was also determined trying to correlate with clinical outcome. Strains isolated of retro-orbital abscess were identified as Rhizopus oryzae. MIC results (MIC) testing conidia showed high sensibility to amphotericin B and itraconazole in comparison to the obtained for terbinafine. The tests in the automated system BCT using hyphae showed sensibility to all tested antifungal agents and the FIC results for combination in vitro between terbinafine and itraconazole showed synergism consistent with the therapeutic success obtained for the patient who received initial treatment with amphotericin B followed for maintenance treatment with the combination itraconazole and

Mortality and Morbidity among COVID-19-Associated Mucormycosis Patients in Iran: A Prospective Cohort Study

Background: The key contribution of this paper is from investigating the mortality and morbidity rates and related factors associated with COVID-19-associated-mucormycosis among Iranian patients. The existing literature is scarce on this topic, particularly in the context of Iran. The present study investigates mortality and morbidity among 62 confirmed COVID-19-associated-mucormycosis Iranian patients in relation to their demographic characteristics, laboratory test results, predisposing factors, and COVID-related factors. Material and Methods: In this prospective cohort study, the patients were identified in the fifth wave of the disease, between 1st August and 15th October 2021, with data collected at baseline with a three-week follow-up. This was a multicenter investigation with patients admitted to two clinics in Iran. 62 participants were admitted, with the key criteria of them being COVID-19-associated-mucormycosis patients. 53 out of 60 patients underwent corticosteroid therapy and debridement surgery. Intravenous remdesivir (200 mg/ kg/day at day 1, 100 mg/kg/day in following days for up to 5 days) and corticosteroids were administered for 53 out 54 patients. Oxygen therapy was only needed for 30% (n = 19) of the patients. Results: A 40% mortality rate was observed within the three-week follow-up, with deaths concentrated among those with controlled diabetes mellitus (61%) and long-term diabetes mellitus patients (an average of eight versus four years). Higher mortality was also observed in patients with higher leucocytes and those with rhino-orbital-cerebral (59%), followed by nasal (55.6%) mucormycosis. Among survivors, 32% were reinfected, and 56% suffered from loss of vision. Conclusion: The study concludes that mucormycosis is associated with a higher mortality rate among COVID-19 patients with diabetes mellitus, particularly corticosteroid recipients. Thus, urgent attention to this coinfection is warranted in Iran.

PULMONARY MUCORMYCOSIS: A CASE REPORT AND SYSTEMIC REVIEW OF LITERATURE

Pulmonary mucormycosis is an increasingly emerging life-threatening infection caused by the order Mucorales (class Zygomycetes). A high index of suspicion in the appropriate clinical setting with prompt diagnosis and optimal treatment is recommended. We made a systemic analysis of 82 reported cases in literature in order to improve clinical knowledge of pulmonary mucormycosis. We described a patient with localized pulmonary mucormycosis diagnosed by histological examination in our hospital. Optimal therapy consists of antifungal medication, surgical resection and control of the patient's underlying illness.