An Unusual Presentation of Rhino-Orbital Mucormycosis with MDR-TB: an Unforeseen Challenge for Treatment Post COVID-19

Abstract

ROCM is an invasive fungal infection that has seen a substantial rise in the post covid-19 patients. Here we present an intriguing case of ROCM existing as a coinfection with MDR-TB. The purpose of this manuscript is to highlight the dilemma faced by the clinicians whether to take the risks associated with standard treatment protocols of mucormycosis contraindicated due to coexisting MDR-TB or to play safe and face the consequences of inadequate management.

Introduction

ROCM is an angioinvasive opportunistic fungal infection caused by mold fungi Rhizopus, Mucor, Rhizomucor of order-Mucorales that classically begins in the paranasal sinuses spreading towards the orbit, maxilla and intracranially occuring almost exclusively in immunocompromised patients. Among the immunodeficient patients, it is most frequently associated with DM, steroids, radiation therapy etc. Tuberculosis affects millions of people mostly in developing countries like India; for 2020, an estimated 18.05 lakh people were notified for tuberculosis infection and only 2.2–3.5% patients are newly diagnosed MDR-TB [1].

In this manuscript, we try to elaborate the presenting clinical features of a patient with concomitant infection of ROCM and MDR-TB, and how both the diseases affected the course of management.

Case Presentation

A 51 yr old female patient presented in the ENT OPD with the complaints of paraesthesia of face, nasal discharge, eye watering and headache on right side since 20 days. She also complained of cough with expectoration. She was recently diagnosed with DM post COVID-19 infection (admitted in the hospital for 17 days, was on oxygen support via high flow mask and was given intravenous methylprednisolone for 14 days). On examination, patient was oriented to time, place and person with vitals being stable. Black brown discharge seen in right nasal cavity, but the signs of extensive disease like blackening of the palate or loosening of teeth not seen. No orbital involvement seen in the form of chemosis/ periorbital swelling/ blurring of vision or proptosis.

Owing to the symptoms and the diabetic status of the patient post covid-19 infection, along with the R/I, we also advised nasal endoscopic biopsy and HbA1c. Punch biopsy sent from the right middle turbinate for KOH mount and fungal staining came positive for aseptate broad fungi and diagnosis of mucormycosis was established. To see the extent of the disease, CEMRI Brain + Orbit + PNS was done.

HbA1c was highly raised with a value of 12.6%.

Chest X-Ray PA view done as a part of the R/I revealed a large thick walled cavity with air fluid level in left lower zone. To explore this incidental finding, patient underwent CECT thorax as advised in TB-CHEST reference, and it suggested a large thick walled cavity with air fluid level in left lower lobe along with mild pleural effusion on left side. Fluid aspirated and sent for R/I. Also patient’s sputum smear was sent for acid fast bacilli which came out to be negative, however; R/I of aspirated fluid indicated tubercular pleural effusion (Table 1). Thereafter, cartridge based nucleic acid amplification test of sputum was done which revealed mycobacterium tuberculosis with rifampicin resistance. Second line-line probe assay revealed mycobacterium tuberculosis sensitive for Fluoroquinolones and second line injectable drugs. Sputum for KOH also came out to be negative and in sputum fungal C/S no organisms found. This ruled out pulmonary mucormycosis.

Table 1.

Routine investigation for fluid aspirated from lung

Sr. No	Test	Value
1	Adenosine deaminase (ADA)	74
2	Protein	52 g/l
3	LDH	800 mcg/l
4	Lymphocytes	85%
5	Mesothelial cells	5%

CEMRI Brain + Orbit + PNS indicate mucosal abnormality involving right ethmoid, maxillary, frontal & bilateral sphenoid sinuses. Also, right retromaxillary fat, infratemporal fossa, peri-optic CSF space was involved.

Therefore, the diagnosis of ROCM with MDR-TB was established.

Course and Treatment

Patient was planned for endonasal endoscopic debridement as the surgical management for mucormycosis. But pleural involvement and lung cavitation rendered the patient vulnerable for difficult extubation, high risk for ventilator dependence and early demise. Owing to the high risk, patient gave negative consent for general anaesthesia. Medical management was started with intravenous liposomal amphotericin B 5 mg/kg (350 mg)-after pre hydration with 500 ml normal saline, liposomal amphotericin 350 mg is diluted with D5% 500 ml + 8 units of HIR. Strict monitoring of electrolytes and urea, creatinine done. Simultaneously, patient was taken on shorter regimen for MDR-TB containing high dose isoniazid, pyrazinamide, ethambutol, high dose moxifloxacillin, ethionamide, cycloserine and kanamycin. Within 3 days, we shifted from amphotericin B to posaconazole due to deranged RFT (Table 2).

Table 2.

Renal function test before and after amphotericin B administration

Sr. N0	Test	Before starting amphotericin B & kanamycin	3rd day of amphotericin B & kanamycin
1	Urea	18 mg/dl	47 mg/dl
2	Creatinine	1.1 mg/dl	3.3 mg/dl

Patient soon started developing uneasiness in the chest and after 6 days, repeat chest X-Ray revealed air fluid levels on right side. Ultrasonography of chest depicted minimal pleural effusion (Fig. 1).

Fig. 1.

CECT thorax showing cavity left lung

Repeat CEMRI Brain + Orbit + PNS done after 10 days with a cumulative dose of 1050 gm of liposomal amphotericin B and 2400 mg of intravenous posaconazole suggested mild reduction in the maxillary sinus disease with enhancement along the right intracranial fossa floor(Fig. 2).

Fig. 2.

CEMRI showing disease in right paranasal sinuses and perioptic space reaching upto intracranial fossa floor

Despite all the treatment, patient’s general condition kept on declining with decreasing appetite and increasing respiratory distress. After 12–13 days of medical management patient’s saturation started dropping and was put on invasive ventilation along with life saving drugs. Patient died after 14 days.

Discussion

It has now been established in many studies that COVID-19 infection has led to an immoderate increase in the number of mucormycosis cases. One of the reasons being excessive steroid intake during its course of treatment and many speculations regarding the association between two are still being made. Mucormycosis has been associated with DM, particularly in uncontrolled hyperglycemia leading to ketoacidosis. Also diabetic patients are susceptible to develop TB, have higher chances of treatment failure as hyperglycemic environment favors suppressed immune functions. In studies done by Deepak et al. in 2015, Pratibha et al. in 2016, Jimenez et. al and many others, pulmonary mucormycosis and TB has been seen in the same patienst occurring as a co-infection [2–4].

But for ROCM and MDR-TB to Occur Simultaneously, in Our Knowledge this is the First Reported Case in this Post COVID-19 Era of ROCM

Our patient gave no history of prior symptoms of tubercular infection or antitubercular treatment and was newly diagnosed with MDR-TB which can be credited to the highly immunocompromised state owing to covid-19 infection.

It is considered that active TB infection occurs only when the immunity is compromised, but recent studies uncover the evidence that TB infection can also infact lead to an immunocompromised state. In our case, an immunosuppressant state prevailing as result of DM and MDR-TB rendered the patient highly susceptible to the infection of ROCM.

Both of these infections are quiet unrelated to each other in terms of its course of involvement, symptoms and essentially the management.

As stated in a study by Balai et. al in 2020, the definitive management of ROCM is surgical debridement combined with intravenous antifungal medication[5]. As stated earlier, surgical debridement was not done. Also liposomal amphotericin B(drug of choice in mucormycosis) was stopped after 3 days since patient’s urea & creatinine were getting deranged. The reason being combined nephrotoxicity due to amphotericin B and kanamycin.

CONCLUSION- Since the patient was unfit for general anaesthesia, she could not undergo surgical debridement and the medical management was sabotaged by the drug interaction of amphotericin B(drug of choice for mucormycosis) with another nephrotoxic drug kanamycin(essential part of MDR-TB regimen). The inadequate management of this deadly infection called mucormycosis in our opinion led to demise of the patient. But the dilemma still persists that could we have saved the patient if we went overboard with all the anticipated risks.

Abbreviations

ROCM

Rhino-orbital-cerebral mucormycosis

MDR-TB

Multidrug resistant tuberculosis

DM

Diabetes Mellitus

R/I

Routine investigations

Authors contribution

Study was done under the guidance of Dr. SG. Data collection and manuscript writing was done by Dr. PA and Dr. RJ.

Funding

Not applicable.

Data availability

Can be made available at request.

Declarations

Conflict of interest

Not applicable.

Consent to participate

Obtained from the institution’s ethical committee.

Ethical approval

Obtained from the institution’s ethical committee.