Abstract

Coronavirus disease-2019 (COVID-19) pandemic caused millions of people to become infected and had resulted several deaths. After initial resolution, in cases of clinical deterioration, it is essential to consider the possibility of coinfections. Non-tuberculousmycobacteria infections are rare and often overlooked. In this report, we present a severe acute respiratory syndrome-Coronavirus-2 and Mycobacterium fortuitum coinfected patient. Our intention is to bring attention to the possibility of such coinfection without a known history of any lung diseases or immunosuppression other than COVID-19 and thus, broadening the clinical thinking process of physicians.

Introduction

There are nearly 200 species of non-tuberculous mycobacteria (NTM), most of which live in soil and water in rural and urban areas (1). Almost half have been associated with opportunistic infections in animals and humans, causing sporadic outbreaks (1). NTM is acquired through exposure to water, aerosols, soil and dust via inhalation, ingestion, cracks due to skin injuries, surgical procedures, or catheterization (1). Almost all patients with NTM pulmonary disease have chronic or recurring cough. Other symptoms include sputum, fatigue, malaise, dyspnea, fever, hemoptysis, chest pain, and weight loss (1). Both 2020 “Treatment of Non-tuberculous Mycobacterial Pulmonary Disease” clinical practice guideline and expert panel group for management recommendations in NTM pulmonary diseases recommend using clinical (pulmonary symptoms, and exclusion of other diagnoses), radiographical (nodular or cavitary opacities on chest radiograph, or an high resolution computed tomography (CT) scan that shows multifocal bronchiectasis with multiple small nodules), and microbiological (positive cultures from at least two separate expectorated sputum samples, or one positive culture from bronchial lavage or biopsy) criteria for diagnosis (2, 3).

A recent review assessing the prevalence of bacterial coinfection in Coronavirus disease-2019 (COVID-19) patients showed that the coinfection rate was between 2.5-5.1% (4). Although there are only a few studies dedicated to NTM coinfections, one case report stated a Mycobacterium abscessus and severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) coinfection in a patient with underlying multiple myeloma (5).

In this report, we present a SARS-CoV-2 and Mycobacterium fortuitum coinfected patient without a known history of any lung diseases or immunosuppression other than COVID-19.

Case Presentation

A 44-year-old male patient with hypertension presented with fever, cough, and shortness of breath. The patient’s SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) test was positive and he was on fifth day of treatment with favipiravir and acetylsalicylic acid. The physical examination showed body temperature of 36.3 °C, heart rate of 92/min, arterial blood pressure of 120/70 mmHg, oxygen saturation of 95% in room air by pulse oximeter and bilateral diffuse rales. The initial laboratory findings were as follows: leukocytes 5150x10⁶/L, neutrophil 4070x10⁶/L, lymphocyte 720x10⁶/L, platelet 153x10⁹/L, lactate dehydrogenase 344 U/L, D-dimer 1375 ng/mL, fibrinogen 3.27 g/L, ferritin 1585 ng/mL, C-reactive protein 71mg/L, procalcitonin 0.218 ng/mL. CT pulmonary angiogram showed diffuse multilobed, multifocal, predominantly peripherally located, ground glass consolidations with approximately 25-50% of lung parenchyma being affected (Figure 1).

The patient was admitted to COVID-19 ward and the treatment was rearranged as favipiravir 2x600 mg tb, enoxaparin 2x0.4 cc sc and acetylsalicylic acid 1x100 mg tb. During his 2^nd day at the ward, methylprednisolone 1x80 mg IV was started upon the need for 2 Lt/min nasal oxygen support. Due to onset of fever (38.3 °C), increase of cough, new sputum complaints and significant rise in D-dimer levels (9767 ng/mL), CT pulmonary angiogram was repeated on 6^th day of follow-up. The result revealed significant progression with approximately 50-75% of the lung parenchyma being affected (Figure 2). Accompanying laboratory results are summarized in Table 1. Antimicrobial therapy was initiated: meropenem 3x1 gr IV and tygecycline 2x50 mg IV following 1x100 mg IV loading dose. No growth in blood and urine culture was detected. Serum cytomegalovirus PCR, Galactomannan and Aspergillus spp. PCR, and sputum Pneumocystis jirovecii PCR were negative, as well. Evaluation of the gram-stained sputum smear under ×100 magnification revealed <10 epithelial cells and >25 polymorphonuclear leukocytes per field, but no microorganisms were detected. Routine sputum culture showed no microbial growth after 24 hours of incubation at 35 °C on blood agar, eosin methylene blue agar, and chocolate agar. While sputum Erlich Ziehl Neelsen stain was negative, NTM were grown in mycobacteria culture medium on the 7^th day of incubation. On the 16^th day of in-hospital follow-up, the patient was discharged with the treatment plan as clarithromycin, rifampicin, and ethambutol and frequent follow-up appointments. The bacteria was found to be Mycobacterium fortuitum which was resistant to clarithromycin, ciprofloxacin and doxycycline and sensitive to moxifloxacin, amikacin and linezolid. Clarithromycin was displaced by moxifloxacin in treatment regimen. Upon clinical improvement, triple regimen was administered for six months till two consequtive sputum samples were negative for NTM.

Discussion

Mycobacterium fortuitum has been previously identified as the causative microorganism of skin and soft tissue infections, including post-surgery or post-traumatic nosocomial infections via comtaminated medical devices in immunocompetent patients (6, 7). Although Mycobacterium fortuitum was associated with serious and life-threatening infections in immunocomprised patients before, there are also a few case reports defining pulmonary involvement in otherwise healthy patients, as well (8-10). While there are several reports indicating a rise in NTM infections in recent years, to the best ouf our knowledge there are no reports describing a pulmonary NTM involvement in a COVID-19 patient without any underlying pulmonary diseases (11).

Mycobacterium fortuitum is a common microorganism of environment and surfaces. Therefore, as mentioned in previous sections, it requires at least two positive cultures to conclude a patient with a diagnosis of pulmonary Mycobacterium fortuitum infection. In the presented case, although treatment was initiated before the growth of Mycobacterium fortuitum in the second sputum sample, the improvement in clinical symptoms following therapy and the growth of Mycobacterium fortuitum following sputum cultures strongly suggest the definitive diagnosis.

The identification of NTM at the species level is clinically important because treatment and response rates vary depending on different subtypes (12). Anti-microbial susceptibility testing breakpoints to guide the management of rapidly growing mycobacteria infections have been recently established and updated in “CLSI M24S-ED2: 2023 Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes, 2^nd edition” (13). In light of the current literature, it is suggested to treat NTM infections with more than one antimicrobial for a prolonged duration (14). Therefore, growing NTM in our patient’s sputum sample was sent to Republic of Türkiye, Ministry of Health, General Directorate of Public Health National Tuberculosis Reference Laboratory, and the patient was treated for more than six months with three agents.

The presence of SARS-CoV-2 infection in our case may have caused a defect in the respiratory tract epithelial tissue. We assume that SARS-CoV-2 infection and corticosteroid therapy may also be a facilitating factor for NTM infection in our patient because of generating possible immunosuppression. This assumption needs to be studied further.

Conclusion

In conclusion, with NTM being on the rise and the severity of coinfections in COVID-19, this case report was presented to shed light on this topic and to bring awareness to the possible coinfection of Mycobacterium fortuitum and SARS-CoV-2.