key: cord-0755304-ed23dy6q authors: Soman, Rajeev; Chakraborty, Sourabh; Joe, Geethu title: Posaconazole or Isavuconazole as sole or predominant anti-fungal therapy for COVID-19 associated Mucormycosis. A retrospective observational case series date: 2022-04-09 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2022.04.009 sha: 417ba34ce882d7bcc6d8c3d5a548655b820461f0 doc_id: 755304 cord_uid: ed23dy6q The surge of COVID-19 associated Mucormycosis (CAM) in India during the second wave of COVID-19 led to lack of availability of amphotericin B(AmB). We retrospectively evaluated the outcome in 28 consecutive patients with CAM who received posaconazole (PCZ) or isavuconazole (ISVCZ) as sole or predominant therapy, based on factors like availability, affordability, site of infection or lack of treatment response. Therapeutic drug monitoring was used for PCZ in all cases & for ISVCZ in some cases. Higher trough levels were aimed to ensure therapeutic effect. Overall, 16 patients were cured, 5 patients improved, 6 patients died, of which 2 deaths were attributable to mucormycosis and 1 patient was lost to follow-up. The outcomes and survival were comparable to those reported in the literature. Although wider applicability of these results cannot be assumed, it leads to a speculation that treatment of mucormycosis with PCZ or ISVCZ, without AmB, is possible.  Posaconazole/Isavuconazole were used for treatment of COVID19 associated mucormycosis  Out of the 28 consecutive patients, 21 patients were cured or improved and 7 died  These outcomes compare favourably with those reported in the literature  It may be speculated that mucormycosis may be treated solely with these new Azoles rhinosinusitis, palate and skull base in 1 patient; rhinosinusitis and skull base in 5 patients; rhinosinusitis and orbit in 4 patients; rhinosinusitis, orbit and brain in 2 patients; rhinosinusitis, orbit, brain and skull base in 1 patient; rhinosinusitis, orbit, brain and ophthalmic involvement in 1 patient; rhinosinusitis, orbit, ophthalmic and skull base involvement in 2 patients; rhinosinusitis and brain in 1 patient; pulmonary involvement in 5 patients; pulmonary, orbit and ophthalmic involvement in 1 patient. Underlying co- cases & for ISVCZ in some cases. Usually recommended therapeutic levels are > 1.2 mg/L for PCZ and TDM for ISVCZ is usually not recommended but the trough level is thought to be 3 mg/L with usual doses. PCZ levels between 2.5-3 mg/L & ISVCZ levels between 5-7 mg/L were aimed for assurance of adequate penetration to the sites of infection. Depending on the earlier mentioned factors 4 patients were treated with ISVCZ alone (initial IV loading dose followed by tablet ISVCZ), 3 patients were treated with PCZ alone (initial IV loading dose followed by gastro resistant (GR) PCZ tablet), 2 patients were treated with ISVCZ followed by G.R PCZ (as ISVCZ was not available), 2 patients were treated with G.R PCZ followed by ISVCZ (in view of bony involvement), 9 patients were treated with IV PCZ and AmB (in perioperative period ranging from 4-13 days) followed by G.R PCZ, 4 patients were treated with IV PCZ and AmB (in perioperative period ranging from 8-11 days) followed by ISVCZ (in view of intra cranial extension, orbital or bony involvement), 4 patients were treated with AmB and PCZ elsewhere (ranging from 28 d -52 d) followed by G.R PCZ. Treatment duration was based on clinical, radiological and microbiological stability and improvement. This needed a long time of treatment in some patients as has been reported in the literature 1 . 16 patients were cured with treatment, the duration of which ranged from 65 days to 219 days & remained well during a follow-up which ranged from 154 to 290 days. 5 patients improved and are still on treatment as of 23 rd Feb 2022, the duration of which has ranged from 238 days to 309 days. 6 patients died, of which 2 deaths were attributable to Mucormycosis & had received treatment, the duration of which ranged from 4 to 24 days. 1 critically ill patient left the hospital as relatives had decided to limit treatment. Hence, he is presumed to have died soon afterwards. These outcomes & survival compare favourably with those reported in the literature. Crude mortality in this series was 25% as compared to reported mortality which ranges from 19% to 45.7% in various publications 3, 4, 5, 6 . Although wider applicability of these results cannot be assumed, it leads to a speculation that treatment of Mucormycosis with PCZ or ISVCZ, without AmB, is possible. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium Isavuconazole Treatment of Invasive Fungal Sinusitis: A Post Hoc Analysis of the SECURE and VITAL Trials Isavuconazole treatment for mucormycosis: a single-arm open-label trial and casecontrol analysis Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial Multicenter Epidemiologic Study of Coronavirus Disease-Associated Mucormycosis, India. Emerg Infect Dis Matchedpaired analysis of patients treated for invasive mucormycosis: standard treatment versus posaconazole new formulations (MoveOn)