CASE-LETTER
Mycobacterium abscessus as a Cause of Chronic Meningitis: A Rare Clinical Entity ycobacterium abscessus is a rapidly growing nontuberculous mycobacterium (RGM). It is a saprophyte, which is ubiquitous in soil, dust and water in natural ecosystems. In the last 2 decades, it has emerged as a cause of both community-acquired and hospital-acquired infections. This rare pathogen is most frequently associated with skin and soft-tissue infections after injury or surgery, with pulmonary disease in patients suffering from cystic fibrosis and with disseminated disease in immune-compromised patients. Only 3 cases of central nervous system (CNS) infection with this organism have been reported in literature.1 In this Grand Round, we describe a case of chronic meningitis caused by M. abscessus and review the literature on this topic. A 59-year-old man was admitted with presenting complaints of cognitive decline, anorexia with lassitude and low-grade fever for 3 months' duration. His medical history revealed history of right-side ventriculoperitoneal (VP) shunt insertion in 1990 for a clinical diagnosis of tubercular meningitis with hydrocephalus. He had a shunt revision after a year for proximal blockage. He was managed with antitubercular (ATT) drug therapy for 15 months and was asymptomatic for next 16 years. In the year 2008, he sustained multiple lacerated, incised and bite wounds all over his body in a scuffle. He was admitted in altered sensorium and managed conservatively in a tertiary-care hospital. Radiological findings were within normal limits and shunt was functional. After this incident, he suffered gradual global deterioration with cognitive decline, upward gaze paresis, ataxic gait and low-toned voice. Since last 3 months, he had high-grade fever with drowsiness. His neuroradiological evaluation showed features of raised intracranial tension with hydrocephalus. His neurologic status deteriorated after admission and diagnostic shunt tap was performed. The cerebrospinal fluid (CSF) examination was suggestive of ventriculitis. Cytologic analysis revealed increased white blood cell counts with predominant lymphocytes. Biochemical analysis of CSF showed raised protein and normal sugar. Acid-fast staining showed predominant acid-fast bacilli. The CSF sample was cultured on blood agar, MacConkey agar, chocolate agar and Lowenstein-Jensen medium. In 48 hours, culture showed acid-fast bacilli and Gram-negative bacteria identified to be Klebsiella pneumonae sensitive to chloramphenicol and meropenem. The acid-fast bacilli were identified to be M. abscessus by conventional biochemical tests. A blood culture report just before his admission here also revealed growth of M. abscessus sensitive to amikacin and clarithromycin.
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Subsequently, he was kept on intravenous antibiotics (amikacin, clarithromycin and meropenem). The VP shunt was removed because of the suspicion of possible colonization, and right frontal horn external ventricular drainage (EVD) was inserted. After 3 sterile cultures, EVD was removed and shunt was reinserted. After 1 week of procedure, he again developed fever and deterioration in neurologic status. Shunt was exteriorized and later replaced with right temporal Ommaya reservoir and left temporal long-tunnel EVD. The ventriculitis did not respond to antibiotic treatment, as spontaneous mutations affecting the principal targets are reported in M. abscessus.2 He eventually succumbed to the infection despite all possible efforts. (Figure) An RGM is a distinct class of nonpigmented mycobacteria belonging to Runyon group IV, which show growth on solid media within 7 days. The RGM are inherently resistant to first-line ATT.3 The genetic evaluation of 16sRNA gene sequence categorizes RGM as phylogenetically older and distinct from slow-growing mycobacteria. The RGM consists of about 40 recognized species among which main source of human infections are M. abscesus, Mycobacterium chelonae and Mycobacterium fortuitum. These 3 pathogens are responsible for 90% of clinical disease. In the earlier classification system, M. abscessus was classified as a subspecies of M. chelonae but current taxonomy classifies it as a separate species. In comparison to slowgrowing mycobacteria, the RGM are less well known as a cause of morbidity and mortality. M. abscessus is a ubiquitous commensal saprophyte in various natural resources, especially aquatic ecosystems. The RGM is a commensal flora in respiratory, gastrointestinal and urogenital tract. Approximately 55% of water supplies in dialysis centers and 30-78% of soil specimen contain these organisms. Mycobacterial growths between 103-105 CFU/cm2 may be present on some surfaces. The capability of biofilm formation is a survival strategy for these organisms. The species is highly hydrophobic in nature and forms a good amount of biofilm. In fact, their existence in early biofilm in water pipelines makes them a real pioneer in biofilm formation. The favorable conditions for growth include aquatic habitat, moderate temperature, organic sources such as plastic and rubber and continuous flow of water. It is tolerant to high temperatures and chemical disinfectants such as chlorine and gluteraldehyde. Though there are case reports throughout the world, some outbreaks of M. abscessus have also been reported predominantly from American continent suspecting role of environmental factors (Table, Supplemental Digital Content 1). There is no history of human-to-human transmission and most of the outbreaks are reported from faulty sterilization techniques in hospitals or cross-contamination in laboratory settings. The RGM are capable of forming biofilms explaining the long latent period and resistance to routine drug treatment. Among all RGM, M. abscessus is most commonly associated with chronic lung disease, chronic
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AFB & AFB AFB GNB Admission with fever and neurological signs November 9
VP shunt removed and frontal horn EVD done
final outcome
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January 28
EVD was removed and shunt re-inserted.
1 week later
Shunt was exteriorised
Right Temporal Ommaya reservoir placed
Intravenous Anbiocs : Amikacin, Meropenem, Clarithromycin
FIGURE. CSF profile and management during the hospital stay. AFB, acid-fast bacilli; GNB, Gram-negative bacilli.
otitis media and post–trauma settings. The disease has a variable latent period ranging from weeks to years and the course is unpredictable. Characteristic clinical findings are skin nodules and pulmonary infiltrates. Patients with cystic fibrosis are at special risk to acquire pulmonary disease due to M. abscessus. The treatment in such cases should be started without delay in the view of disease severity and therapeutic resistance of the organism. Literature review reveals 19 cases of CNS infection by RGM. Among these, M. abscessus was the identified pathogen in 3 cases (Table, Supplemental Digital Content 1). Among all RGM, M. abscessus is most commonly isolated from pulmonary infections. The first case report of M. abscessus infection was reported in 1953 by Moore and Freirichs, where it was isolated from the synovial fluid and gluteal abscess of the same patient.3 The CNS involvement in M. abscessus is very rare. There are only 3 case reports published in the English-language literature worldwide but none from India.4-6 This case is unique in demanding a discussion on the possible route of inoculation of the organism. The 2 possible ways of infection are during history of trauma in 2008 or nosocomial infection during repeat shunt or Ommaya insertion. Literature reveals outbreaks of M. abscessus in nosocomial settings but predominant organs affected are lungs and skin. In 3 previous cases of CNS infection, the presenting symptomatology is meningitis with variable duration of symptoms ranging from weeks to months. It is difficult to treat M. abscessus infections. The organism is intrinsically resistant to first-line ATT drugs. Drugs that have minimal inhibitory concentrations less
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than the tissue or serum levels are clarithromycin, aminoglycosides, cefoxitin, tigecycline and TMC-207.7 Choice of antibiotic should be based on susceptibility testing and extent of disease. Even after prolonged incubation (14 days), if the strains are sensitive to the tested drugs, it indicates a favorable prognosis especially with the combination therapy.7 The organism has the tendency to accumulate multiple spontaneous mutations that are the key targets for the recommended drugs like aminoglycosides and macrolides. Macrolides are also affected by inducible erm gene mutation.2 These mutations ultimately affect the treatment outcome. As the organism has a tendency of biofilm formation, authors recommend removal of the infected implants namely, VP shunt, Ommaya reservoir or venous catheters. Both intravenous and intrathecal routes should be utilized for effective CSF penetration. The duration of treatment is not yet standardized. However, few case reports recommend more than a year treatment for serious systemic infections. Repeated CSF culture can guide the management. Drugs should be continued for months even after a negative CSF culture. Role of steroids is still not clear; authors of lone survivor in this series have recommended concomitant steroid therapy in patients nonresponsive to antimicrobial therapy or among those with severe chronic meningitis on presentation.4 This case highlights the need of high index of suspicion in diagnosing this rare pathogen. The RGM should be kept in the differential diagnosis of suspected pathogens in patients with history of trauma or hospitalization. The long latent period in this case doubts the role of the particular event in pathogenesis. The difficulty
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Chronic Meningitis by Mycobacterium Abscessus
in diagnosing, relative resistance to drug therapy, doubtful role of steroids, long duration of treatment and poor survival rate lays down responsibility on caregivers for prompt reporting of this infection to prevent crosscontamination. Reports of hospital outbreaks demand rechecking of sterilization measures.
Appendix A. Supplementary Information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/ 10.1016/j.amjms.2016.02.009. Ankita Baidya, MD Manjul Tripathi, MCh Pooja Pandey, MSc *Urvashi B. Singh, MD, PhD Department of Neurosurgery, AIIMS, New Delhi, India *(E-mail:
[email protected]). The authors have no financial or other conflicts of interest to disclose.
REFERENCES
1. Lee MR, Cheng A, Lee YC, et al. CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates. J Antimicrob Chemother 2012;67:222–5. 2. Nessar R, Cambau E, Reyrat JM, et al. Mycobacterium abscessus: a new antibiotic nightmare. J Antimicrob Chemother 2012;67:810–8. 3. Moore M, Freirichs JB. An unusual acid-fast infection of the knee with subcutaneous abscess-like lesions of the gluteal region: report of a case with a study of the organism Mycobacterium abscessus. J Invest Dermatol 1953;20:133–69. 4. Talati NJ, Rouphael N, Kuppalli K, et al. Spectrum of CNS disease caused by rapidly growing mycobacteria. Lancet Infect Dis 2008;8: 390–398. 5. Maniu CV, Hellinger WC, Chu SY, et al. Failure of treatment for chronic Mycobacterium abscessus meningitis despite adequate clarithromycin levels in cerebrospinal fluid. Clin Infect Dis 2001;33:745–8. 6. Liebeskind DS, Ostrzega N, Wasterlain CG, et al. Neurologic manifestations of disseminated infection with Mycobacterium abscessus. Neurology 2001;56:810–3. 7. Koh WJ, Jeon K, Lee NY, et al. Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med 2011;183:405–10.
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