P086 Clinical outcome and in vitro antifungal susceptibility of clinical isolates of rhino-orbito-cerebral mycosis associated with post COVID 19 from North India
Authors: Taneja Juhi , Chatterjee Kuhu , Sasidharan Jaseetha , Abbas Zafar , Rai Anil K , Das Bhabatosh 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
This study aimed primarily to determine the etiology, clinical features, and comorbidities of patients with rhino-orbito-cerebral mycosis. Secondly, antifungal susceptibility pattern of the isolates and lineage by ITS-sequencing was also studied.

Methods
The study was conducted from May to December 2021 on all suspected cases of rhino-orbito-cerebral mycosis in post-COVID-19 patients at a tertiary care center. Data pertaining to demographics, recent COVID-19 infection, clinical features, comorbidities, laboratory, radiological investigations, management, and outcomes were collected after obtaining informed consent from all patients. Staging of ROCM was done using the proposed code Mucor and diagnosis of COVID-19 was done on basis of real-time polymerase chain reaction (RT-PCR) test. KOH Mount examination, fungal culture, and histopathological examination was performed on samples collected endoscopically or post-debridement. Mucormycosis was proven based on fungal culture or specific histological features from biopsy specimens. In vitro susceptibility profiles for antifungal drugs as per CLSI microbroth dilution method (M38-A2) was studied by HiMIC™ plate (HiMedia) for amphotericin B, voriconazole, posaconazole, itraconazole, and isavuconazole. MIC ranges and the drug concentrations required to inhibit 50% (MIC50) or 90% of isolates (MIC90) were determined. ITS Sequencing was also performed on representative isolates.

Results
A total of 70 patients were diagnosed with mucormycosis. Rhino-orbital and rhino-orbito-cerebral forms were observed in 35.7% of cases each. Diabetes mellitus (DM) was present in 95.7% patients while 78.5% of the patients were treated with corticosteroids in recent past, and 25.7% presented with active COVID-19 pneumonia. Most cases showed onset of symptoms of mucormycosis between 29 ± 17 days from diagnosis of COVID-19. On imaging, orbit was involved in 52.8% and cranial involvement is seen in 35.7% of patients. Diagnosis of mucormycosis was established on KOH direct microscopy 68.6%, culture 47.14%, histopathology 55.7%. Isolates obtained were Rhizopus arrhizus (42.4%), Apophysomyces variabilis (3.03%), and Aspergillus spp (69.7%) while mixed infection was seen in 42.4%. The MIC50 and MIC90 of amphotericin B for R. arrhizus strains were 0.25 and 4 μg/ml; and MIC50 and MIC90 results for itraconazole, posaconazole, and isavuconazole were 8 and 8, 2 and 2, and 2 and 8 μg/ml respectively. Aspergillus spp was susceptible to amphotericin B (38.8%), itraconazole (50%), voriconazole (50%), posaconazole (11.1%), and isavuconazole (44.4%). Overall treatment included intravenous amphotericin B along with functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 68.2%, orbital exenteration in 4.2%, orbital decompression in 11.4% patients and partial maxillectomy in 22.8% cases. Intraorbital injection of amphotericin B was administered in 15.7%. At final follow-up, mortality was 19.7%. In vitro MICs showed that amphotericin B was the most active compound against most species.

Conclusion
High index of suspicion, early diagnosis, and appropriate management of mucormycosis can improve survival. Rational use of steroids and strict glycemic control in diabetic patients can prevent occurrence of mucormycosis. Use of standard methods for antifungal susceptibility testing to guide antifungal treatment may be clinically useful in cases of treatment failure.