The Pediatric Infectious Disease Journal • Volume 34, Number 2, February 2015
due to pharmacologic respiratory depression. Her gastrointestinal symptoms were resolved by the fourth day after admission. Laboratory data were as follows: leukocyte count, 7400/mL; lymphocyte count, 1800/mL without other alterations. Glucose, 81 mg/dL; ammonium, 51 IU/L and serum electrolytes were in normal range. Venous blood gases showed metabolic acidosis. Urine studies were negative. CSF revealed leukocytes, 5/mL, protein, 21 mg/dL and glucose, 59 mg/dL. An electroencephalogram showed slow and disorganized cerebral activity. Cerebral magnetic resonance imaging and computerized tomography showed no abnormalities. To elucidate the pathogen associated with her neurologic symptoms, CSF was examined at the hospital laboratory by polymerase chain reaction (PCR) following the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology viral meningitis protocol7 and the guidelines on evaluation of encephalitis published by Venkatesan et al.8 PCR for Herpes simplex virus 1–2, enterovirus and respiratory viruses (respiratory syncytial virus, rhinovirus, coronavirus, parainfluenza 1,2,3,4, influenza A including H1N1, influenza B, adenovirus, metapneumovirus and bocavirus) and serology for Mycoplasma pneumoniae were performed in CSF, all of which were negative. A second CSF sample showed no cytologic alterations, negative anti-N-methyl D-aspartate antibodies and neopterin levels of 80 nmol/L (N: 8–43) with normal biopterin. After PICU discharge, she was only treated with valproic acid and she continued with extrapyramidal movements. These symptoms improved after extubation, but residual dysphagia to liquids and mild contraction tremor occurred. She was discharged after 16 days with valproic acid treatment. Suspecting viral encephalitis diagnosis associated with diarrhea upon admission, CSF sample was sent to the Viral Gastroenteritis Unit—Instituto de Salud Carlos III (ISCIII). A NoV genome was detected in 2 different samples of CSF and 1 stool sample by using conventional reverse transcription PCR9 followed by sequence analysis with the reverse transcription PCR products used for NoV genotyping as previously described.10 NoV strain sequences were characterized as GII.4 in all 3 samples.
DISCUSSION This is the first time in Spain and the second worldwide6 that the genome of NoV from the stool sample and the 2 CSF samples were genetically characterized and matched. These results indicate that NoV may be the cause of the encephalitis symptoms described above. Neurologic manifestations associated with norovirus infection in children, particularly benign afebrile seizures had been described in last years,11,12 but the presence of norovirus had been confirmed in the central nervous system.13 The results of this study also support previous findings and contribute additional evidence that NoV may be the cause of viral encephalitis and further research is needed. REFERENCES 1. Junquera CG, de Baranda CS, Mialdea OG, Serrano EB, Sánchez-Fauquier A. Prevalence and clinical characteristics of norovirus gastroenteritis among hospitalized children in Spain. Pediatr Infect Dis J. 2009;28:604–607. 2. Verhoef L, Kouyos RD, Vennema H, et al. Foodborne Viruses in Europe Network. An integrated approach to identifying international foodborne norovirus outbreaks. Emerg Infect Dis. 2011;17:412–418. 3. Kato Z, Manabe T, Teramoto T, Kondo N. Adenovirus infection mimics the cerebellitis caused by rotavirus infection. Eur J Pediatr. 2011;170:405–406. 4. Kimura E, Goto H, Migita A, et al. An adult norovirus-related encephalitis/ encephalopathy with mild clinical manifestation. BMJ Case Rep. 2010;18:2010. 5. Glass RI, Parashar UD, Estes MK. Norovirus Gastroenteritis. N Engl J Med 2009; 361:1776–1785. 6. Ito S, Takeshita S, Nezu A, et al. Norovirus-associated encephalopathy. Pediatr Infect Dis J. 2006;25:651–652. 7. Navarro Marí JM, Pérez Ruiz M, Vicente A. Laboratory diagnosis of lymphocytic meningitis. Enferm Infecc Microbiol Clin. 2010;28(suppl 1):56–61.
© 2014 Wolters Kluwer Health
Norovirus-associated Encephalitis
8. Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;57:1114–1128. 9. Gonzalez-Galan V, Sánchez-Fauquier A, Obando I, et al. High prevalence of community-acquired norovirus gastroenteritis among hospitalized children: a prospective study. Clin. Microbiol. Infect 2011;17:1895–1899. 10. Sánchez-Fauquier A, Wilhelmi I, Roman E, et al. Surveillance of human calicivirus in Spain. Emerg Infect Dis. 2005;11:1327–1329. 11. Medici MC, Abelli LA, Dodi I, Dettori G, Chezzi C. Norovirus RNA in the blood of a child with gastroenteritis and convulsions – a case report. J Clin Virol 2010;48:147. 12. Obinata K, Okumura A, Nakazawa T, et al. Norovirus encephalopathy in a previously healthy child. Pediatr Infect Dis J 2010;29:1057. 13. Kawano G, Oshige K, Syutou S, et al. Benign infantile convulsions associate with mild gastroenteritis: a retrospective study of 30 cases including virological tests and efficacy of anticonvulsants. Brain Dev 2007;29:617.
INTRACRANIAL MYCOBACTERIUM ABSCESSUS INFECTION IN A HEALTHY TODDLER Julie S. Martin, MD,* David Zagzag, MD, PhD,†‡ Maureen Egan, MD,§ Sarah Milla, MD,¶ David Harter, MD,‡ and Jennifer Lighter-Fisher, MD‖ Abstract: We present the first case of pediatric intracranial Mycobacterium abscessus infection in a 16-month-old female with neurofibromatosis type 1. We describe a successful treatment regimen including excisional biopsy combined with high-dose steroids and 16 weeks of triple antimicrobial therapy that resulted in clinical cure and an excellent neurologic outcome. Key Words: M. abscessus, brain/pathology, pediatric, Mycobacterium infections/microbiology/therapy, female, humans Accepted for publication August 13, 2014. From the *Department of Pediatrics, Georgia Regents University/University of Georgia Health Sciences Campus, Athens, GA; †Department of Pathology; ‡Department of Neurosurgery; §Department of Pediatrics, New York University School of Medicine, New York, NY; ¶Department of Pediatric Radiology, Children’s Hospital of Atlanta, Atlanta, GA; and ║Saul Krugeman Division of Pediatric Infectious Diseases and Immunology, New York University School of Medicine, New York, NY. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Julie Martin, MD, Department of Pediatrics, Georgia Regents University/University of Georgia Health Sciences Campus, 1425 Prince Avenue, Athens, GA. E-mail: [email protected]. Copyright © 2014 by Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/INF.0000000000000520
I
t is unusual for rapidly growing mycobacteria to invade the central nervous system (CNS). It has only been reported in immunocompromised hosts, individuals who recently experienced trauma or brain surgery and in those with contiguous spread from middle ear infections.1,2 We describe the clinical features and successful treatment outcome of the first reported case of Mycobacterium abscessus complex CNS infection in a previously healthy toddler.
CASE A 16-month-old female with neurofibromatosis type 1 (NF1) presented with a 3-week history of post-tussive emesis, decreased energy and appetite. No fever was reported until 1 day before admission when she had a temperature of 38.2°C axillary. Her past medical history was unremarkable and she had received all immunizations appropriate for her age. Physical examination on admission was normal. Laboratory evaluation was remarkable for a leukocytosis of 38 × 109/L with 70% neutrophils. She was started on ceftriaxone for suspected pyelonephritis based on urinalysis. A lumbar puncture was subsequently performed because of an acute change in mental status; www.pidj.com | 223
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Martin et al
cerebral spinal fluid (CSF) white blood cells were 11,000 cells/μL with 81% neutrophils, 54 red blood cells/μL, protein level was 191 mg/dL and glucose level was 21 mg/dL. Gram stain was negative. Vancomycin was added to her regimen empirically. Her fever resolved and the vomiting improved. Blood and CSF cultures remained negative. On the sixth day of hospitalization, she became febrile and emesis recurred. Complete blood count demonstrated increased leukocytosis and thrombocytosis. Magnetic resonance imaging (MRI) of the brain revealed a cystic lesion in the left frontal lobe with extension into the lateral ventricle. No sinus or oto-mastoid disease was noted. CSF specimens were negative for acid-fast bacilli by smear and culture. A tuberculin skin test was nonreactive. Metronidazole was empirically added to her regimen for treatment of a presumed bacterial brain abscess. Repeat MRI performed 5 weeks into therapy revealed solidification of the cystic lesion and multiple new areas of enhancement. Multiple enlarged lymph nodes were noted on physical examination. CSF was analyzed for fungus, toxoplasmosis, cysticerosis and treponoma—all were negative. Dilated eye examination was normal. Stool ova and parasites microscopy were negative. Repeat tuberculin skin test and interferon gamma (IFN-γ) release assay were negative. Brain biopsy was nondiagnostic. Follow-up excisional brain biopsy revealed granulomatous findings with mycobacterium on the acid-fast smear. The patient was started on dexamethasone at 6 mg/kg/day, and empiric therapy for presumed tuberculosis. Subsequently, the culture grew Mycobacterium abscessus complex. Therapy was changed to intravenous imipenem and amikacin and oral clarithromycin. High-dose dexamethasone was continued for 4 weeks followed by a prolonged taper. The organism was susceptible to amikacin, clarithromycin, intermediate to imipenem. She was continued on triple antimicrobial therapy for 16 weeks. Follow-up MRI studies showed resolution of mass lesions and decrease in inflammation. One and a half years following the completion of therapy the patient continues to have appropriate growth and development without recurrence of illness. She has persisting yet improving deficits, mild language and motor delay. Immunologic work has been unremarkable.
DISCUSSION Diagnosis of M. abscessus is often challenging. Most patients have an indolent course, with a mean duration of symptoms of 6 weeks before presentation.3 Unlike that observed with Mycobacterium tuberculosis infection, there is often neutrophilic pleocytosis in the CSF. Biopsy findings are nonspecific.4 Diagnosis in our patient was only possible after repeat brain biopsy, which revealed granulomas on pathology and yielded a positive culture. This was despite a high index of suspicion for mycobacterial disease with multiple prior cultures of CSF, blood, urine, feces and prior brain biopsy. The etiology of infection in this case remains elusive. All prior reports on cranial M. abscessus infections have been of adults within 3 clinical scenarios such as immunosuppression, introduction of the organism following surgery or trauma and contiguous spread from oto-mastoiditis.2–4 Host defense against mycobacterial infections depends on the ability of monocytes to produce interleukin (IL)-12 and the activation of T-cells to produce IFN-γ. An IL-12 receptor defect has been reported in conjunction with NF1.5 In our patient, T-cell stimulation assays with BCG showed normal levels of IFN-γ and IL-12, and thus ruled out this immune deficiency. NF1 has been associated with other immune deficiencies such as
224 | www.pidj.com
hypogammaglobulinemia but immune globulin levels were normal in our patient.6 It is possible that the child initially had a brain abscess caused by a more common organism, that is, Staphylococcus aureus (antibiotics prior to lumbar puncture interrupted culture growth), and that the M. abscessus was introduced at the time of neurosurgical intervention. In this case, there was no known breach of sterile technique or subsequent contact with nonsterile water or ice. There have been no controlled clinical trials of treatment. M. abscessus is naturally resistant to conventional first-line antituberculous drugs. The complex hydrophobic cell wall of M. abscessus creates an efficient permeability barrier to most antibiotics. Natural and acquired antibiotic resistance often occurs and relapse of M. abscessus complex is common.4 Clarithromycin has historically been the mainstay of oral therapy but should always be used in a multidrug regimen because inducible resistance to macrolides may occur. The utility of other antimicrobials varies with the organism and resistance testing is recommended for invasive infections. Although M. abscessus is a rare intracranial pathogen and has not previously been reported in the pediatric population, our case highlights several potential risk factors including CNS instrumentation and a potential underlying immune deficiency. The genetic abnormalities associated with NF1 increase the risk for malignancies and myelodysplastic disease and may also predispose to immune deficiency as rare associations have been reported. Thus, there remains a possibility of a yet to be diagnosed immune defect in this patient given her underlying condition. The case provides additional insight as we demonstrate a successful treatment regimen for a pathogen that typically is challenging to treat and carries a poor prognosis. Only half of the reported cases of CNS M. abscessus infection have survived and, among the survivors, all received a prolonged duration clarithromycin-based combination therapy usually in combination with surgical debridement.2 Successful treatment courses range from 4 months to a year._ENREF_5 Steroid administration has also been suggested as an adjunct to treatment. Our patient achieved clinical cure with excisional biopsy of the primary lesions along with 4 weeks of high-dose dexamethasone and 16 weeks of imipenem, amikacin and clarithromycin. REFERENCES 1. Liebeskind DS, Ostrzega N, Wasterlain CG, Buttner EA. Neurologic manifestations of disseminated infection with Mycobacterium abscessus. Neurology. 2001;56:810–813. 2. 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;67:222–225. 3. Talati NJ, Rouphael N, Kuppalli K, Franco-Paredes C. Spectrum of CNS disease caused by rapidly growing mycobacteria. Lancet Infect Dis. 2008;8:390–398. 4. Sungkanuparph S, Sathapatayavongs B, Pracharktam R. Infections with rapidly growing mycobacteria: report of 20 cases. Int J Infect Dis. 2003;7:198–205. 5. Luangwedchakarn V, Jirapongsaranuruk O, NiemeLa JE, et al. A novel mutation of the IL12RB1 gene in a child with nocardiosis, recurrent salmonellosis and neurofibromatosis type I: first case report from Thailand. Asian Pac J Allergy Immunol. 2009;27:161–165. 6. Kilic S, Tezcan I, Sanal O, Ersoy F. Common variable immunodeficiency in a patient with neurofibromatosis. Pediatr Int.. 2001;43:691–693.
© 2014 Wolters Kluwer Health
due to pharmacologic respiratory depression. Her gastrointestinal symptoms were resolved by the fourth day after admission. Laboratory data were as follows: leukocyte count, 7400/mL; lymphocyte count, 1800/mL without other alterations. Glucose, 81 mg/dL; ammonium, 51 IU/L and serum electrolytes were in normal range. Venous blood gases showed metabolic acidosis. Urine studies were negative. CSF revealed leukocytes, 5/mL, protein, 21 mg/dL and glucose, 59 mg/dL. An electroencephalogram showed slow and disorganized cerebral activity. Cerebral magnetic resonance imaging and computerized tomography showed no abnormalities. To elucidate the pathogen associated with her neurologic symptoms, CSF was examined at the hospital laboratory by polymerase chain reaction (PCR) following the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology viral meningitis protocol7 and the guidelines on evaluation of encephalitis published by Venkatesan et al.8 PCR for Herpes simplex virus 1–2, enterovirus and respiratory viruses (respiratory syncytial virus, rhinovirus, coronavirus, parainfluenza 1,2,3,4, influenza A including H1N1, influenza B, adenovirus, metapneumovirus and bocavirus) and serology for Mycoplasma pneumoniae were performed in CSF, all of which were negative. A second CSF sample showed no cytologic alterations, negative anti-N-methyl D-aspartate antibodies and neopterin levels of 80 nmol/L (N: 8–43) with normal biopterin. After PICU discharge, she was only treated with valproic acid and she continued with extrapyramidal movements. These symptoms improved after extubation, but residual dysphagia to liquids and mild contraction tremor occurred. She was discharged after 16 days with valproic acid treatment. Suspecting viral encephalitis diagnosis associated with diarrhea upon admission, CSF sample was sent to the Viral Gastroenteritis Unit—Instituto de Salud Carlos III (ISCIII). A NoV genome was detected in 2 different samples of CSF and 1 stool sample by using conventional reverse transcription PCR9 followed by sequence analysis with the reverse transcription PCR products used for NoV genotyping as previously described.10 NoV strain sequences were characterized as GII.4 in all 3 samples.
DISCUSSION This is the first time in Spain and the second worldwide6 that the genome of NoV from the stool sample and the 2 CSF samples were genetically characterized and matched. These results indicate that NoV may be the cause of the encephalitis symptoms described above. Neurologic manifestations associated with norovirus infection in children, particularly benign afebrile seizures had been described in last years,11,12 but the presence of norovirus had been confirmed in the central nervous system.13 The results of this study also support previous findings and contribute additional evidence that NoV may be the cause of viral encephalitis and further research is needed. REFERENCES 1. Junquera CG, de Baranda CS, Mialdea OG, Serrano EB, Sánchez-Fauquier A. Prevalence and clinical characteristics of norovirus gastroenteritis among hospitalized children in Spain. Pediatr Infect Dis J. 2009;28:604–607. 2. Verhoef L, Kouyos RD, Vennema H, et al. Foodborne Viruses in Europe Network. An integrated approach to identifying international foodborne norovirus outbreaks. Emerg Infect Dis. 2011;17:412–418. 3. Kato Z, Manabe T, Teramoto T, Kondo N. Adenovirus infection mimics the cerebellitis caused by rotavirus infection. Eur J Pediatr. 2011;170:405–406. 4. Kimura E, Goto H, Migita A, et al. An adult norovirus-related encephalitis/ encephalopathy with mild clinical manifestation. BMJ Case Rep. 2010;18:2010. 5. Glass RI, Parashar UD, Estes MK. Norovirus Gastroenteritis. N Engl J Med 2009; 361:1776–1785. 6. Ito S, Takeshita S, Nezu A, et al. Norovirus-associated encephalopathy. Pediatr Infect Dis J. 2006;25:651–652. 7. Navarro Marí JM, Pérez Ruiz M, Vicente A. Laboratory diagnosis of lymphocytic meningitis. Enferm Infecc Microbiol Clin. 2010;28(suppl 1):56–61.
© 2014 Wolters Kluwer Health
Norovirus-associated Encephalitis
8. Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;57:1114–1128. 9. Gonzalez-Galan V, Sánchez-Fauquier A, Obando I, et al. High prevalence of community-acquired norovirus gastroenteritis among hospitalized children: a prospective study. Clin. Microbiol. Infect 2011;17:1895–1899. 10. Sánchez-Fauquier A, Wilhelmi I, Roman E, et al. Surveillance of human calicivirus in Spain. Emerg Infect Dis. 2005;11:1327–1329. 11. Medici MC, Abelli LA, Dodi I, Dettori G, Chezzi C. Norovirus RNA in the blood of a child with gastroenteritis and convulsions – a case report. J Clin Virol 2010;48:147. 12. Obinata K, Okumura A, Nakazawa T, et al. Norovirus encephalopathy in a previously healthy child. Pediatr Infect Dis J 2010;29:1057. 13. Kawano G, Oshige K, Syutou S, et al. Benign infantile convulsions associate with mild gastroenteritis: a retrospective study of 30 cases including virological tests and efficacy of anticonvulsants. Brain Dev 2007;29:617.
INTRACRANIAL MYCOBACTERIUM ABSCESSUS INFECTION IN A HEALTHY TODDLER Julie S. Martin, MD,* David Zagzag, MD, PhD,†‡ Maureen Egan, MD,§ Sarah Milla, MD,¶ David Harter, MD,‡ and Jennifer Lighter-Fisher, MD‖ Abstract: We present the first case of pediatric intracranial Mycobacterium abscessus infection in a 16-month-old female with neurofibromatosis type 1. We describe a successful treatment regimen including excisional biopsy combined with high-dose steroids and 16 weeks of triple antimicrobial therapy that resulted in clinical cure and an excellent neurologic outcome. Key Words: M. abscessus, brain/pathology, pediatric, Mycobacterium infections/microbiology/therapy, female, humans Accepted for publication August 13, 2014. From the *Department of Pediatrics, Georgia Regents University/University of Georgia Health Sciences Campus, Athens, GA; †Department of Pathology; ‡Department of Neurosurgery; §Department of Pediatrics, New York University School of Medicine, New York, NY; ¶Department of Pediatric Radiology, Children’s Hospital of Atlanta, Atlanta, GA; and ║Saul Krugeman Division of Pediatric Infectious Diseases and Immunology, New York University School of Medicine, New York, NY. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Julie Martin, MD, Department of Pediatrics, Georgia Regents University/University of Georgia Health Sciences Campus, 1425 Prince Avenue, Athens, GA. E-mail: [email protected]. Copyright © 2014 by Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/INF.0000000000000520
I
t is unusual for rapidly growing mycobacteria to invade the central nervous system (CNS). It has only been reported in immunocompromised hosts, individuals who recently experienced trauma or brain surgery and in those with contiguous spread from middle ear infections.1,2 We describe the clinical features and successful treatment outcome of the first reported case of Mycobacterium abscessus complex CNS infection in a previously healthy toddler.
CASE A 16-month-old female with neurofibromatosis type 1 (NF1) presented with a 3-week history of post-tussive emesis, decreased energy and appetite. No fever was reported until 1 day before admission when she had a temperature of 38.2°C axillary. Her past medical history was unremarkable and she had received all immunizations appropriate for her age. Physical examination on admission was normal. Laboratory evaluation was remarkable for a leukocytosis of 38 × 109/L with 70% neutrophils. She was started on ceftriaxone for suspected pyelonephritis based on urinalysis. A lumbar puncture was subsequently performed because of an acute change in mental status; www.pidj.com | 223
The Pediatric Infectious Disease Journal • Volume 34, Number 2, February 2015
Martin et al
cerebral spinal fluid (CSF) white blood cells were 11,000 cells/μL with 81% neutrophils, 54 red blood cells/μL, protein level was 191 mg/dL and glucose level was 21 mg/dL. Gram stain was negative. Vancomycin was added to her regimen empirically. Her fever resolved and the vomiting improved. Blood and CSF cultures remained negative. On the sixth day of hospitalization, she became febrile and emesis recurred. Complete blood count demonstrated increased leukocytosis and thrombocytosis. Magnetic resonance imaging (MRI) of the brain revealed a cystic lesion in the left frontal lobe with extension into the lateral ventricle. No sinus or oto-mastoid disease was noted. CSF specimens were negative for acid-fast bacilli by smear and culture. A tuberculin skin test was nonreactive. Metronidazole was empirically added to her regimen for treatment of a presumed bacterial brain abscess. Repeat MRI performed 5 weeks into therapy revealed solidification of the cystic lesion and multiple new areas of enhancement. Multiple enlarged lymph nodes were noted on physical examination. CSF was analyzed for fungus, toxoplasmosis, cysticerosis and treponoma—all were negative. Dilated eye examination was normal. Stool ova and parasites microscopy were negative. Repeat tuberculin skin test and interferon gamma (IFN-γ) release assay were negative. Brain biopsy was nondiagnostic. Follow-up excisional brain biopsy revealed granulomatous findings with mycobacterium on the acid-fast smear. The patient was started on dexamethasone at 6 mg/kg/day, and empiric therapy for presumed tuberculosis. Subsequently, the culture grew Mycobacterium abscessus complex. Therapy was changed to intravenous imipenem and amikacin and oral clarithromycin. High-dose dexamethasone was continued for 4 weeks followed by a prolonged taper. The organism was susceptible to amikacin, clarithromycin, intermediate to imipenem. She was continued on triple antimicrobial therapy for 16 weeks. Follow-up MRI studies showed resolution of mass lesions and decrease in inflammation. One and a half years following the completion of therapy the patient continues to have appropriate growth and development without recurrence of illness. She has persisting yet improving deficits, mild language and motor delay. Immunologic work has been unremarkable.
DISCUSSION Diagnosis of M. abscessus is often challenging. Most patients have an indolent course, with a mean duration of symptoms of 6 weeks before presentation.3 Unlike that observed with Mycobacterium tuberculosis infection, there is often neutrophilic pleocytosis in the CSF. Biopsy findings are nonspecific.4 Diagnosis in our patient was only possible after repeat brain biopsy, which revealed granulomas on pathology and yielded a positive culture. This was despite a high index of suspicion for mycobacterial disease with multiple prior cultures of CSF, blood, urine, feces and prior brain biopsy. The etiology of infection in this case remains elusive. All prior reports on cranial M. abscessus infections have been of adults within 3 clinical scenarios such as immunosuppression, introduction of the organism following surgery or trauma and contiguous spread from oto-mastoiditis.2–4 Host defense against mycobacterial infections depends on the ability of monocytes to produce interleukin (IL)-12 and the activation of T-cells to produce IFN-γ. An IL-12 receptor defect has been reported in conjunction with NF1.5 In our patient, T-cell stimulation assays with BCG showed normal levels of IFN-γ and IL-12, and thus ruled out this immune deficiency. NF1 has been associated with other immune deficiencies such as
224 | www.pidj.com
hypogammaglobulinemia but immune globulin levels were normal in our patient.6 It is possible that the child initially had a brain abscess caused by a more common organism, that is, Staphylococcus aureus (antibiotics prior to lumbar puncture interrupted culture growth), and that the M. abscessus was introduced at the time of neurosurgical intervention. In this case, there was no known breach of sterile technique or subsequent contact with nonsterile water or ice. There have been no controlled clinical trials of treatment. M. abscessus is naturally resistant to conventional first-line antituberculous drugs. The complex hydrophobic cell wall of M. abscessus creates an efficient permeability barrier to most antibiotics. Natural and acquired antibiotic resistance often occurs and relapse of M. abscessus complex is common.4 Clarithromycin has historically been the mainstay of oral therapy but should always be used in a multidrug regimen because inducible resistance to macrolides may occur. The utility of other antimicrobials varies with the organism and resistance testing is recommended for invasive infections. Although M. abscessus is a rare intracranial pathogen and has not previously been reported in the pediatric population, our case highlights several potential risk factors including CNS instrumentation and a potential underlying immune deficiency. The genetic abnormalities associated with NF1 increase the risk for malignancies and myelodysplastic disease and may also predispose to immune deficiency as rare associations have been reported. Thus, there remains a possibility of a yet to be diagnosed immune defect in this patient given her underlying condition. The case provides additional insight as we demonstrate a successful treatment regimen for a pathogen that typically is challenging to treat and carries a poor prognosis. Only half of the reported cases of CNS M. abscessus infection have survived and, among the survivors, all received a prolonged duration clarithromycin-based combination therapy usually in combination with surgical debridement.2 Successful treatment courses range from 4 months to a year._ENREF_5 Steroid administration has also been suggested as an adjunct to treatment. Our patient achieved clinical cure with excisional biopsy of the primary lesions along with 4 weeks of high-dose dexamethasone and 16 weeks of imipenem, amikacin and clarithromycin. REFERENCES 1. Liebeskind DS, Ostrzega N, Wasterlain CG, Buttner EA. Neurologic manifestations of disseminated infection with Mycobacterium abscessus. Neurology. 2001;56:810–813. 2. 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;67:222–225. 3. Talati NJ, Rouphael N, Kuppalli K, Franco-Paredes C. Spectrum of CNS disease caused by rapidly growing mycobacteria. Lancet Infect Dis. 2008;8:390–398. 4. Sungkanuparph S, Sathapatayavongs B, Pracharktam R. Infections with rapidly growing mycobacteria: report of 20 cases. Int J Infect Dis. 2003;7:198–205. 5. Luangwedchakarn V, Jirapongsaranuruk O, NiemeLa JE, et al. A novel mutation of the IL12RB1 gene in a child with nocardiosis, recurrent salmonellosis and neurofibromatosis type I: first case report from Thailand. Asian Pac J Allergy Immunol. 2009;27:161–165. 6. Kilic S, Tezcan I, Sanal O, Ersoy F. Common variable immunodeficiency in a patient with neurofibromatosis. Pediatr Int.. 2001;43:691–693.
© 2014 Wolters Kluwer Health
