Extrapulmonary infections associated with nontubercular mycobacteria in immunocompetent patients: A study of two cases

Yukti Sharma; Susheel Kumar Chumber; Saumya Saxena; Krishna Vaitheeswaran; Neelam Gera

doi:10.4103/IJAM.IJAM_56_17

CASE REPORT

Year : 2018 | Volume : 4 | Issue : 2 | Page : 169-172

Extrapulmonary infections associated with nontubercular mycobacteria in immunocompetent patients: A study of two cases

Yukti Sharma¹, Susheel Kumar Chumber¹, Saumya Saxena², Krishna Vaitheeswaran², Neelam Gera¹
¹ Department of Microbiology, St. Stephen's Hospital, New Delhi, India
² Department of Opthalmology, St. Stephen's Hospital, New Delhi, India

Date of Submission	24-May-2017
Date of Acceptance	19-Dec-2017
Date of Web Publication	30-Aug-2018

Correspondence Address:
Dr. Yukti Sharma
272 SFS DDA Flats, Mukherjee Nagar, New Delhi - 110 009
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/IJAM.IJAM_56_17

Abstract

Nontuberculous mycobacteria (NTM) or atypical mycobacteria are abundantly found in the environment. Extrapulmonary infections are most commonly caused by Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium, and Mycobacterium kansasii. Risk factors for infection include both accidental/surgical trauma, all procedures involving implants, retained biomaterial. The isolation rate of NTM from India has been reported ranging from 0.5% to 8.6%. We report two culture-proven cases of infection caused by NTM. The present cases emphasize the importance of considering NTM in the differential diagnosis of nonhealing ulcers whether corneal or skin and soft tissue infections.
The following core competencies are addressed in this article: Medical knowledge, Patient care.

Keywords: Delhi, Mycobacterium avium complex, nontuberculous mycobacteria, non-healing ulcer

How to cite this article:
Sharma Y, Chumber SK, Saxena S, Vaitheeswaran K, Gera N. Extrapulmonary infections associated with nontubercular mycobacteria in immunocompetent patients: A study of two cases. Int J Acad Med 2018;4:169-72

How to cite this URL:
Sharma Y, Chumber SK, Saxena S, Vaitheeswaran K, Gera N. Extrapulmonary infections associated with nontubercular mycobacteria in immunocompetent patients: A study of two cases. Int J Acad Med [serial online] 2018 [cited 2022 Jun 27];4:169-72. Available from: https://www.ijam-web.org/text.asp?2018/4/2/169/240140

Introduction

Nontuberculous mycobacteria (NTM) or atypical mycobacteria are abundantly found in the environment. The protean manifestations include ocular involvement, chronic leg ulcers, soft tissue infections, lymphadenitis, septic arthritis, bone, and disseminated infection. The species of NTM usually associated with extrapulmonary infections are Mycobacterium chelonac, Mycobacterium fortuitum, Mycobacterium avium, and Mycobacterium kansasii. Risk factors for infection include both accidental/surgical trauma; all procedures involving implants retained biomaterial.^[1],[2] Pulmonary tuberculosis has been reported, by far, more in comparison to NTM in India as a result of the practice to report the latter as contaminants. NTM infections are usually subjected to difficulty in identification; hence, the diagnosis along with the condition being prolonged due to refractory therapies.

The delayed identification and diagnosis thereby leads to a delayed treatment with patient ending up with use of topical corticosteroids,^[2] refractory to multiple medical therapies and surgical interventions. Data regarding incidence of extrapulmonary NTM in the US are unclear; 10% of NTM disease manifesting as extrapulmonary has been reported. Mortality rate from NTM deaths in the United States is growing. According to the population-based data (1999 through 2010) of US, the mean age-adjusted mortality rate of 0.1 per 100,000 person-years was seen. It was also reported as an immediate cause of death in 2990 people.^[3] Being considered an important cause of morbidity and mortality in Western countries, NTM in India still faces prejudice regarding diagnosis. There is a dearth of data regarding the pathogenic behavior of NTM in our country. We report herein culture-proven cases of infection caused by NTM.

Case Reports

Case 1

An 18-year-old male patient presented with sharp continuous intraocular pain of the right eye associated with photophobia and watering for 10 days' duration. He was in good general health. There was no history of any systemic diseases, recent ocular trauma, ocular surgery, or contact lens use. He visited the local practitioner but the ailment did not respond to the prescribed medications. At presentation to this hospital, visual acuity was positive to light perception. Slit lamp biomicroscopy of the right eye revealed a paracentral 3 mm diameter ring-like, dry corneal ulcer from 10 to 12 o'clock position superiorly 2 mm away from limbus with underlying stromal edema. Circumcorneal congestion was present with no satellite lesions. Anterior chamber showed mild reaction with 1 + cells and hypopyon was present. Corneal sensations were normal in both eyes. Fundus examination was normal. No abnormality was detected in lacrimal sac examination. Systemic examination revealed no lymphadenopathy and clear respiratory system. Scraping was done after instilling local anesthesia with sterile number 15 scalpel blade. The scrapings were inoculated onto culture media and smeared on glass slides directly and sent for microbiological examination.

Case 2

A 60-year-old female presented with a nonhealing ulcer, associated with pain and swelling, over the right proximal leg. Local examination revealed a 3 cm × 2 cm, irregular, nonhealing ulcer along with slough, minimal purulent discharge. There was no localized rise of temperature. She had uncontrolled diabetes, diagnosed 5 years back. Systemic examination was normal. She was afebrile at time of presentation. Her vitals were stable. Pus swabs were collected twice, on two separate occasions and sent to the microbiology laboratory.

Materials and Methods

Staining was done with Gram and Ziehl–Neelsen (ZN) stains (Hi-Media, Mumbai, India). The specimen was streaked on blood agar (BA, containing 5% sheep blood) and MacConkey agar, chocolate agar, brain heart infusion broth and incubated at 37°C aerobically up to 48 h. For isolation of fungi, the specimens were cultured on Sabouraud dextrose agar (containing chloramphenicol 50 μg/ml) in duplicate. Plates were incubated at 37°C and 22°C both and observed for growth, if any, up to 3 weeks. The isolated organisms were identified as per the standard bacteriological techniques.

Gram staning showed few Gram positive bacteria ZN stain was positive for acid- fast bacilli (decolorizing wth 20% H₂ SO₄) indicating mycobacterium. Culture on BA revealed circular, smooth, pale cream colonies. To identify microorganism, its phenotypic characteristics were used. Identification to species level was achieved on the basis of the growth characteristics, including growth in <7 days, growth at 37°C, pigment production. Based on the results of these key tests, all isolates were identified as M. fortuitum - M. chelonae complex.

Antimicrobial susceptibility testing for the rapidly-growing NTM was carried out on Mueller Hinton agar by the disc diffusion Kirby–Bauer method to the following antibiotics: chloramphenicol (10 μg), erythromycin (15 μg), tetracycline (30 μg), ciprofloxacin (5 μg), amikacin (30 μg), ofloxacin (5 μg), piperacillin (100 μg), cotrimoxazole (25 μg), rifampicin (5 μg), streptomycin (10 μg), gentamicin (10 μg), tobramycin and polymyxin B 300, all were sensitive.

Discussion

Nontubercular mycobacteria are present in natural waters and soils worldwide. The pathogenic potential of NTM species is influenced by the immunological status of the patient and the site from which the culture was taken. They are opportunistic pathogens that are increasingly being recognized as important causes of skin and soft tissue diseases. NTM infections can mimic as fungal, herpetic, or amoebic keratitis in cases of ocular lesions. This further causes a delay in diagnosis and hence treatment. Differential diagnosis includes nonmycobacterial spp. such as Nocardia, Rhodococcus, cysts of Cryptosporidium, and Isospora spp showing varying degree of acid-fastness. Rapidly growing mycobacteria are important human pathogens and have been reported from postsurgical wound infections in many countries including India,^[1] apart from being a pathogen in corneal ulcers.^[4]

The isolation rate of NTM from India has been reported ranging from 0.5% to 8.6%. The NTM isolation rate of 3.5% has been reported among the seronegative (immunocompetent) patients.

A study from Guwahati reported 20 NTM (M. fortuitum - M. chelonae complex) out of 25 pus culture specimens from cases of delayed onset of postoperative wound infections. Another study from Saudi Arabia observed 27.1% of total clinical samples to be NTM from extrapulmonary sources. In contrast, a study from Vellore reported 3.9% (173 of 4473) grew NTM from various clinical specimens.^[4] A study from Taiwan reported a significant increase in NTM isolation and a decreasing isolation of Mycobacterium tuberculosis (P < 0.05 for each).^[5]

AFB stains show a variable rate of positivity in cases of NTM. A study reported 95% cases of NTM endophthalmitis being ZN stain positive.^[1],[6] Kalita et al. observed that of all clinical specimens, 80% of the specimens were culture positive of which 40% were positive in ZN-stained direct smears.^[1] This propels the need for an initial diagnostic staining for acid-fast organisms, especially in cases of chronic ulcers, difficult diagnosis, or in cases of microbial cultures showing slow growth.

NTM should be considered in the differential diagnosis of nonhealing ulcers, whether corneal or skin and soft tissue infections.^[7],[8] NTM should be suspected even in those patients with no obvious history of trauma since subsequent treatment with appropriate drugs also prevents morbidity in addition to foregoing the need for invasive surgical intervention. Ayyash et al. reported an orbital infection which was confused for pseudotumor and treated accordingly.^[9] A lapse of 26 weeks occurred before it was diagnosed as NTM and then treated accordingly. Apart from delayed diagnosis and delayed treatment, the chances of economic losses, injudicious usage of drugs, side effects, and continued morbidity add to the burden of the disease. There is no evidence to prove that NTM can persist in a dormant state so as to reactivate at a later date as seen in tuberculosis. In the treatment strategy of the present cases, the first case was started on clarithromycin with tobramycin for the ocular infection.^[10] The patient responded very well with vision 6/6 at 2 weeks. Later, the patient left against medical advice and so was lost to follow-up. The second patient had been started on empirical antibiotics such as amikacin and cefoperazone before the culture report was given.

NTM infections have been associated with immunocompromised people, especially PLHA with CD4 count <100, but we hereby report these two cases who were not predisposed otherwise. There is a need to create awareness among clinicians and the microbiologists to have bilateral discussions so that necessary steps are taken to diagnose and likewise treat NTM and thereby generate more data for our country. Uniform documentation and reporting of culture-proven NTM infections from clinical settings along with the sensitivity profiles is the need of the hour.

Conclusion

A nonhealing wound may present a confusing picture, and in such cases, mycobacterial infection should always be ruled out by proper investigations, especially AFB culture. The present cases emphasize the importance of considering NTM in the differential diagnosis of nonhealing ulcers.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kalita JB, Rahman H, Baruah KC. Delayed post-operative wound infections due to non-tuberculous Mycobacterium. Indian J Med Res 2005;122:535-9.
2.	Bhandari V, Relekar K. An unusual case of nonhealing granulomatous keratitis caused by Mycobacterium chelonae in a healthy middle aged adult. Case Rep Ophthalmol Med 2015;2015:708312.
3.	Mirsaeidi M, Machado RF, Garcia JG, Schraufnagel DE. Nontuberculous mycobacterial disease mortality in the United States, 1999-2010: A population-based comparative study. PLoS One 2014;9:e91879.
4.	Katoch VM. Infections due to non-tuberculous mycobacteria (NTM). Indian J Med Res 2004;120:290-304.
5.	Lai CC, Tan CK, Chou CH, Hsu HL, Liao CH, Huang YT, et al. Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000-2008. Emerg Infect Dis 2010;16:294-6.
6.	Kheir WJ, Sheheitli H, Abdul Fattah M, Hamam RN. Nontuberculous mycobacterial ocular infections: A Systematic review of the literature. Biomed Res Int 2015;2015:164989.
7.	Jesudason MV, Gladstone P. Non tuberculous mycobacteria isolated from clinical specimens at a tertiary care hospital in South India. Indian J Med Microbiol 2005;23:172-5. [PUBMED] [Full text]
8.	Jain S, Sankar MM, Sharma N, Singh S, Chugh TD. High prevalence of non-tuberculous mycobacterial disease among non-HIV infected individuals in a TB endemic country – Experience from a tertiary center in Delhi, India. Pathog Glob Health 2014;108:118-22.
9.	Ayyash II, Weatherhead RG, Jacquemin C. Mycobacterium of an unknown strain causing a primary tumoral process of the orbital roof. Orbit 1999;18:281-6.
10.	Brown-Elliott BA, Nash KA, Wallace RJ Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev 2012;25:545-82.