Ocular mycobacteriosis—dual infection of M. tuberculosis complex with M. fortuitum and M. bovis
- Kusum Sharma†1,
- Natasha Gautam†2,
- Megha Sharma1,
- Mohit Dogra2,
- Priya Bajgai2,
- Basavaraj Tigari2,
- Aman Sharma3,
- Vishali Gupta2,
- Surya Prakash Sharma2 and
- Ramandeep Singh2Email author
© The Author(s). 2017
Received: 21 November 2016
Accepted: 27 December 2016
Published: 13 January 2017
We report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of Mycobacterium tuberculosis complex with Mycobacterium fortuitum and Mycobacterium bovis in an immunosuppressed, non-HIV patient. We did a systematic review of literature on dual infection due to M. tuberculosis and M. fortuitum via MEDLINE and PUBMED and could not find any case reported of causing this kind of dual infection in the eye.
A 38-year-old Indian male patient presented with decreased vision in the left eye for 3 months, diagnosed as tubercular choroidal granuloma with associated retinal angiomatosis proliferans (RAP) lesion. He also had multiple enlarged lymph nodes in the chest, and sternal pus sample was positive for acid-fast bacilli (AFB). M. tuberculosis complex was detected by gene expert. The patient was started on antitubercular treatment (ATT) whereby the lung lesions improved but the ocular lesion showed initial clinical improvement followed by worsening. Twenty-five-gauge diagnostic pars plana core vitreous surgery was done whereby sample demonstrated a large number of AFB on Ziehl-Neelsen stain and auramine-rhodamine stain. The vitreous sample showed growth on routinely inoculated mycobacteria growth indicator tube (MGIT) 960 tubes, and multiplex polymerase chain reaction (PCR), Gene Xpert MTB/ RIF assay (Cepheid, Sunnyvale, CA), and line probe assay (LPA) were positive for ocular tuberculosis. In view of nonresponse to conventional ATT, a suspicion of dual infection of M. tuberculosis complex with a nontubercular mycobacteria was kept and a subculture was made onto the solid Lowenstein-Jensen (LJ) medium from the positive MGIT 960 tubes. Two morphologically distinct types of colonies were obtained on LJ slopes. Subsequently, the two etiological agents were identified as M. fortuitum and M. bovis by PCR from the vitreous sample.
Co-infection of M. tuberculosis complex with nontubercular mycobacterium (NTM) has never been reported from ocular tuberculosis before. In immunosuppressed individuals, who test positive for MTB, not responding to the standard ATT, one needs to have a high index of clinical suspicion to rule out associated NTM infection and initiate appropriate multidrug systemic antibiotic therapy early.
KeywordsMycobacterium tuberculosis Nontubercular mycobacteria PCR Subretinal granuloma Dual infection Mycobacterium tuberculosis complex Antitubercular therapy
Nontubercular mycobacterium (NTM) infections are difficult to identify thus causing a delay in the diagnosis and treatment . The agents causing NTM infections are found ubiquitously in soil, dust, and water. Human infection is thought to be acquired from environmental exposures . In the literature, only nine cases of uveitis caused by NTM have been reported. Of these, five were detected in immunocompromised patients . We report a novel case of subretinal granuloma caused by dual infection with M. tuberculosis complex and M. fortuitum leading to an unfavorable outcome in a non-HIV patient.
Patient was a farmer by occupation. Past history revealed treatment with pulse dose of intravenous steroids followed by oral steroids at 1 mg/kg body weight, dexamethasone intravitreal implant (Ozurdex, Allergan), and co-trimoxazole for presumed ocular toxoplasmosis. This long-term use of systemic steroids at a high dosage leads to an immunosuppressed state thereby leading to a disseminated form of infection. Past investigations like complete hemogram, VDRL, HIV, HBsAg, Toxo IgG /IgM, and Mantoux test were normal. At our center, examination by internist revealed normal examination except for erythematous area with small pustule on the sternal aspect of chest. Contrast-enhanced computed tomography (CECT) of chest showed loculated pericardial effusion in anterior part along with small foci of subsegmental collapse and bronchiectasis in the left upper lobe, paracardiac part of the right medial lobe and left lingual along with few subcentimeter lymph nodes in the right paratracheal chain. Sternal pus sample was drawn which showed acid-fast bacilli (AFB) on Ziehl-Neelsen staining, and Mycobacterium tuberculosis complex (MTBC) was detected by gene expert.
Oral levofloxacin 500 mg twice a day was added, since the rapid growers like M. fortuitum is found to be sensitive to flouroquinolones (third generation) in addition to the ATT . PET scan revealed intense FDG uptake in the affected eyeball and left supraclavicular, mediastinal, right upper, and lower paratracheal and bilateral hilar lymph nodes. In view of the poor response to treatment, he was investigated to rule out immunosuppression. His CD4 count was very low (2.8%, absolute count—51/μl), with absolute lymphocyte count of 1807/μl. Repeat HIV and HIV-1 proviral DNA were negative. Steroids were stopped, and ATT was continued for a total duration of 1 year. However, we were not able to save the eye anatomically and functionally. At 9 months of follow-up, the left eye had no light perception with phthisis bulbi and the other eye was normal. Repeat PET scan revealed no FDG uptake in the previously involved tissues. Oral isoniazid and rifampicin were continued, while oral levofloxacin was stopped.
In a highly TB-endemic country like ours, ocular tuberculosis is relatively not a rare entity and it occurs mainly in the form of posterior uveitis. Early detection, diagnosis, and appropriate conservative management with antitubercular therapy often yield good results in terms of preservation of vision and restoration of anatomical integrity . Our patient had a large tubercular choroidal granuloma, which tested positive on Ziehl-Neelsen staining and PCR, but with a poor clinical outcome despite initiating ATT. An important reason for the poor outcome could be infection due to the multidrug resistant M. tuberculosis, which was ruled out, by the LPA and Gene Xpert in our case. Gupta et al.  hypothesized that puncturing the granuloma/abscess leads to dissemination of the organisms into the vitreous cavity followed by the development of endophthalmitis that may not be amenable to treatment and may eventually require evisceration. Biswas et al.  reported relatively worse outcome in the eyes subjected to pars plana vitrectomy and drainage of the abscess. However, no attempt was made to either drain or puncture the granuloma during pars plana vitrectomy (PPV) in our case. Thus, we re-evaluated our case to find out the possible causes, and the samples that we obtained during PPV were again subjected to cultures and molecular diagnostics. Our patient now tested positive for a NTM along with M. tuberculosis complex on LJ medium, which was confirmed by PCR. Thus, the presence of dual infection and delay in its diagnosis could be the cause for poor outcome in this case. This could have further been worsened by the concomitant use of intravenous steroids, oral steroids, and dexamethasone implant resulting in low CD4 counts and a disseminated form of infection.
NTM infections are rare, mainly seen in the immunocompromised individuals and often leading to dissemination in the absence of appropriate treatment. In the literature, NTM has been shown as a cause for choroiditis in six eyes, iridocyclitis in one eye, and granulomatous panuveitis in two eyes and treatment with steroids was implicated as a risk factor in 42.9% of the cases . There are four groups of NTM, among which, group IV, i.e., the rapid growers (including M. fortuitum), is the one most commonly infecting the eye as was seen in our case. They do not respond to conventional ATT alone and require a prolonged therapy with multidrug parenteral antibiotics .
Our case also highlights the diagnostic role of molecular methods for these infections in routine laboratories for rapid management and better patient outcome. The role of solid culture in identifying presence of dual infection, which would have been otherwise missed on liquid culture alone, is also important in this case, as previously reported from our center .
In conclusion, the diagnosis of NTM infection and the possibility of it occurring along with MTBC infection require a high index of suspicion on the part of the ophthalmologist and a rapid and reliable diagnosis on the part of the microbiologist. The use of immunosuppressant drugs, atypical features, and poor response to ATT are important clinical pointers towards this rare condition. Confirmatory evidences can be obtained from growth on solid culture media followed by appropriate molecular tests. A delay in diagnosis could lead to irreversible damage as was seen in our case, and thus, prompt initiation of multidrug therapy is often needed. Although our patient lost his vision of one eye, the relatively rapid diagnosis and timely institution of oral levofloxacin (third-generation flouroquinolones), along with stoppage of oral steroids, helped in preventing the dissemination of the infection in the body as was shown by the absence of uptake of FDG in various parts of the body on PET scan.
Contrast-enhanced computerized tomography
- LJ medium:
Line probe assay
Mycobacterium tuberculosis complex
Polymerase chain reaction
- PET scan:
Positron emission tomography scan
Retinal angiomatosis proliferans
NG, KS, and RS contributed to patient management, literature review, and preparation of the manuscript. KS and MS were the microbiologists who contributed to the molecular diagnostic methods for patient management. AS, MD, PB, SP, and BT performed the literature review, data collection, and analysis. RS, KS, and VG provided the concept and design, intellectual content, and critical review of the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
An informed consent was taken from patient.
Grant support/proprietary interest
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, or other equity interest, and expert testimony or patent-licensing arrangements) or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.
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