A metagenomics-based diagnostic approach for central nervous system infections in hospital acute care setting.
Hasan Mohammad Rubayet,Sundararaju Sathyavathi,Tang Patrick,Tsui Kin-Ming,Lopez Andres Perez,Janahi Mohammad,Tan Rusung,Tilley Peter
The etiology of central nervous system (CNS) infections such as meningitis and encephalitis remains unknown in a large proportion of cases partly because the diversity of pathogens that may cause CNS infections greatly outnumber available test methods. We developed a metagenomic next generation sequencing (mNGS)-based approach for broad-range detection of pathogens associated with CNS infections suitable for application in the acute care hospital setting. The analytical sensitivity of mNGS performed on an Illumina MiSeq was assessed using simulated cerebrospinal fluid (CSF) specimens (n = 9). mNGS data were then used as a training dataset to optimize a bioinformatics workflow based on the IDseq pipeline. For clinical validation, residual CSF specimens (n = 74) from patients with suspected CNS infections previously tested by culture and/or PCR, were analyzed by mNGS. In simulated specimens, the NGS reads aligned to pathogen genomes in IDseq were correlated to qPCR C values for the respective pathogens (R = 0.96; p < 0.0001), and the results were highly specific for the spiked pathogens. In clinical samples, the diagnostic accuracy, sensitivity and specificity of the mNGS with reference to conventional methods were 100%, 95% and 96%, respectively. The clinical application of mNGS holds promise to benefit patients with CNS infections of unknown etiology.
Next-generation sequencing specifies Angiostrongylus eosinophilic meningoencephalitis in infants: Two case reports.
RATIONALE:Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis (AEM) in infants is a very rare but fatal disease. Utilization of genetic assay to detect the cerebral parasite plays an important role for the treatment of the infection. PATIENT CONCERNS:Two infants (<2 years) presented with cough, intermittent fever, mental fatigue, and poor diet. DIAGNOSIS:The patients were under clinical examination and laboratory test including cardiac ultrasound, chest X-ray, blood or cerebrospinal fluid (CSF) cell counting, serum enzyme-linked immunosorbent assay (ELISA), head magnetic resonance imaging (MRI) and next-generation sequencing (NGS) on DNA from CSF. Due to hypereosinophils in patients' peripheral blood and CSF, and abundant DNA sequences from A cantonensis in CSF, the patients were diagnosed with Angiostrongylus eosinophilic meningoencephalitis. INTERVENTIONS:The patients were treated with albendazole to deworm, and methylprednisolone to reduce inflammation. OUTCOME:The patients were completely recovered from AEM without relapse after 10-day treatment. LESSONS:ELISA and MRI are not sufficiently accurate for the diagnosis of AEM in infants. NGS can specify the infection by the cerebral parasite and offers a new effective approach for the early and precise diagnosis of AEM in infants.
A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.
Eerkens Jelmer W,Nichols Ruth V,Murray Gemma G R,Perez Katherine,Murga Engel,Kaijankoski Phil,Rosenthal Jeffrey S,Engbring Laurel,Shapiro Beth
International journal of paleopathology
Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans.
Detection of Listeria monocytogenes in a patient with meningoencephalitis using next-generation sequencing: a case report.
Lan Zi-Wei,Xiao Min-Jia,Guan Yuan-Lin,Zhan Ya-Jing,Tang Xiang-Qi
BMC infectious diseases
BACKGROUND:Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. CASE PRESENTATION:We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. CONCLUSION:To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.
Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing.
Stebner A,Ensser A,Geißdörfer W,Bozhkov Y,Lang R
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
OBJECTIVES:Brain abscesses lead to high mortality despite antibiotic and surgical treatment. Identification of causative bacteria is important to guide antibiotic therapy, but culture-based methods and molecular diagnostics by Sanger sequencing of 16S PCR products are hampered by antibiotic treatment and the often polymicrobial nature of brain abscesses. We have applied 16S-rRNA-based next-generation sequencing (NGS) for metagenomic analysis of intracranial abscess (brain and epidural) and meningitis samples. METHODS:Seventy-nine samples from 54 patients with intracranial abscesses or meningitis were included. DNA was subjected to 16S PCR. Amplicons were analysed with the Illumina MiSeq system, sequence reads were blasted versus the NCBI 16S bacterial database and analysed using MEGAN software. Results were compared to those of gram-staining, culture and Sanger sequencing. RESULTS:The NGS workflow was successful for 51 intracranial abscesses (46 brain and five epidural) and nine meningitis samples. Inclusion of (mono)bacterial meningitis samples allowed us to establish a cut-off criterion for the exclusion of contaminating sequences. In total 86 bacterial taxa were identified in brain abscesses by NGS, with Streptococcus intermedius and Fusobacterium nucleatum as most prevalent species; Propionibacterium and Staphylococcus spp. were associated with epidural abscesses. NGS identified two or more bacterial taxa in 31/51 intracranial abscesses, revealing the polymicrobial nature of these infections and allowing the discrimination of up to 16 bacterial taxa per sample. CONCLUSION:These results extend earlier studies showing that NGS methods expand the spectrum of bacteria detected in brain abscesses and demonstrate that the MiSeq platform is suitable for metagenomic diagnostics of this severe infection.
Reduction of Human DNA Contamination in Clinical Cerebrospinal Fluid Specimens Improves the Sensitivity of Metagenomic Next-Generation Sequencing.
Ji Xin-Chao,Zhou Lin-Fu,Li Chao-Yang,Shi Ya-Jun,Wu Meng-Li,Zhang Yun,Fei Xiao-Fei,Zhao Gang
Journal of molecular neuroscience : MN
Metagenomics next-generation sequencing (mNGS) is increasingly available for the detection of obscure infectious diseases of the central nervous system. However, human DNA contamination from elevated white cells, one of the characteristic cerebrospinal fluid (CSF) features in meningitis patients, greatly reduces the sensitivity of mNGS in the pathogen detection. Currently, effective approaches to selectively reduce host DNA contamination from clinical CSF samples are still lacking. In this study, a total of 20 meningitis patients were enrolled, including 10 definitively diagnosed tuberculous meningitis (TBM) and 10 definite cryptococcal meningitis (CM) cases. To evaluate the effect of reduced human DNA in the sensitivity of mNGS detection, three specimen-processing protocols were performed: (i) To remove human DNA, saponin, a nonionic surfactant, was used to selectively lyse white cells in CSF followed by DNase treatment prior to the extraction of DNA; (ii) to reduce host DNA, CSF was centrifuged to remove human cells, and the supernatant was collected for DNA extraction; and (iii) DNA extraction from the unprocessed specimens was set as the control. We found that saponin processing significantly elevated the NGS unique reads for Cryptococcus (P < 0.01) compared with the control but had no effects for Mycobacterium tuberculosis (P > 0.05). However, detection of centrifuged supernatants improved the NGS unique reads for both TBM and CM compared with controls (P < 0.01). Our results demonstrate that the use of mNGS of centrifuged supernatants from clinical CSF samples in patients with TBM and CM is a simple and effective method to improve the sensitivity of pathogen detection.
Metagenomic Next-Generation Sequencing (mNGS) in cerebrospinal fluid for rapid diagnosis of Tuberculosis meningitis in HIV-negative population.
Yan Liping,Sun Wenwen,Lu Zhenhui,Fan Lin
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
OBJECTIVE:Metagenomic Next-Generation Sequencing (mNGS) has been applied as a novel method of detection pathogens for infectious diseases, but its value in the rapid diagnosis of tuberculous meningitis(TBM)has not been clarified based on large samples. METHODS:A retrospective analysis was conducted on 51 inpatients with suspected TBM who underwent mNGS and four other tests in cerebrospinal fluid (CSF). RESULTS:Among 51 included patients, 45 cases were diagnosed as TBM (38 definite, 5 probable, 2 possible) and 6 cases as non-TBM. Using final diagnosis as reference standard, the sensitivity, specificity, PPV (positive predictive value), and NPV (negative predictive value) of mNGS in CSF for TBM were 84.44%(38/45, 69.94%-93.01%), 100%(6/6, 51.68%-100%), 100%(40/40, 88.57%-100%) and 46.15%(6/13, 20.40%-73.88%). The diagnostic sensitivity of mNGS(84.4%)was significantly higher than that of AFB (0%, P = 0.000), MGIT960 culture(22.2%, P = 0.000), MTB PCR(24.4%, P = 0.000) and Xpert MTB/RIF(40%, P = 0.000). The ROC curve showed that CSF protein quantification and CSF cell count might be valuable in the prediction of NGS positive detection of MTB (Mycobacterium tuberculosis). CONCLUSION:CSF mNGS had high sensitivity, specificity and PPV in the diagnosis of TBM. Patients with a significant increase in CSF cell number and protein quantification might have a higher likelihood of positive MTB detection of NGS.
Value of next-generation sequencing in early diagnosis of patients with tuberculous meningitis.
Lin Aiqing,Cheng Baotao,Han Xiaochun,Zhang Hong,Liu Xiaoli,Liu Xueping
Journal of the neurological sciences
OBJECTIVES:To assess the value of next-generation sequencing (NGS) technology in early diagnosis of patients with tuberculous meningitis (TBM). METHODS:56 patients with clinically suspected TBM who came to Shandong Provincial Chest Hospital from February 2, 2018 to August 2, 2018 were prospectively included, and the clinical diagnosis and treatment outcomes were followed up. NGS was performed for the cerebrospinal fluid specimens submitted for test on the BGISEQ-100 platform of Tianjin Huada Gene Research Institute and the obtained pathogen sequences were compared with the pathogen data to get the final results. The NGS results were positive for detecting the unique matching sequence of the Mycobacterium tuberculosis (MTB) complex and negative for no unique matching sequence. Patients confirmed with TBM should have at least one of the following four items: cerebrospinal fluid MTB culture positive, smear positive, Xpert MTB/RIF test positive, or MTB nucleic acid polymerase chain reaction (PCR) test positive; clinically diagnosed patients were those with clinically suspected TBM and effective anti-tuberculosis treatment; non-TBM patients were those with other pathogenic basis or clinical exclusion of TBM. The sensitivity and specificity of NGS in early diagnosis of TBM were analyzed. RESULTS:22 patients were confirmed with TBM, of which 13 were positive for Xpert MTB/RIF test, 6 were positive for cerebrospinal fluid MTB culture, 5 were positive for MTB nucleic acid PCR test, 12 patients were clinically diagnosed with TBM, and there were 16 cases of non-TBM patients. Among confirmed and clinically diagnosed patients, 20 cases of MTB complex were detected by NGS technology, with a sensitivity of 58.8% (20/34) and specificity of 100% (16/16). Among confirmed patients, the sensitivity of NGS was 63.6% (14/22). Of the 50 specimens that were simultaneously subjected to traditional methods, Xpert MTB/RIF test and NGS, the specificity of the three methods was 100% (16/16) based on clinical diagnosis, and the sensitivity was 29.4% (10/34), 38.2% (13/34), and 58.8% (20/34) respectively. The difference of sensitivity between the first two detection methods and NGS was statistically significant (McNemar test, p = 0.013, x = 5.786 and p = 0.065, x = 3.273). The sensitivity of traditional methods combined with NGS was as high as 82.4% (28/34). CONCLUSIONS:NGS technology could rapidly detect the MTB complex in cerebrospinal fluid with significant sensitivity and specificity, which could be used as an early diagnosis index of TBM. NGS combined with MTB culture could increase the detection rate.
Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis.
Wilson Michael R,Sample Hannah A,Zorn Kelsey C,Arevalo Shaun,Yu Guixia,Neuhaus John,Federman Scot,Stryke Doug,Briggs Benjamin,Langelier Charles,Berger Amy,Douglas Vanja,Josephson S Andrew,Chow Felicia C,Fulton Brent D,DeRisi Joseph L,Gelfand Jeffrey M,Naccache Samia N,Bender Jeffrey,Dien Bard Jennifer,Murkey Jamie,Carlson Magrit,Vespa Paul M,Vijayan Tara,Allyn Paul R,Campeau Shelley,Humphries Romney M,Klausner Jeffrey D,Ganzon Czarina D,Memar Fatemeh,Ocampo Nicolle A,Zimmermann Lara L,Cohen Stuart H,Polage Christopher R,DeBiasi Roberta L,Haller Barbara,Dallas Ronald,Maron Gabriela,Hayden Randall,Messacar Kevin,Dominguez Samuel R,Miller Steve,Chiu Charles Y
The New England journal of medicine
BACKGROUND:Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS:In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS:We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS:Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).
Symptomatic Mycobacterium avium complex infection of the central nervous system. A case report and review of the literature.
Gyure K A,Prayson R A,Estes M L,Hall G S
Archives of pathology & laboratory medicine
Mycobacterium avium complex infections rarely involve the central nervous system, even in patients with widely disseminated disease. We report a case of disseminated M. avium complex infection presenting with central nervous system symptoms in a patient with Hodgkin's disease. Neurologic findings included disorientation, nuchal rigidity, seizures, an extensor plantar response, cerebrospinal fluid studies consistent with meningitis, and eventually, coma and death. Organisms of the M. avium complex were cultured from several sites. Histopathologically, the central nervous system lesions consisted of small aggregates of lymphocytes and macrophages containing acid-fast organisms present in a predominantly perivascular location. In view of the life-threatening nature and potential treatability of this uncommon presentation of M. avium complex infection, we suggest that these organisms be sought in immunocompromised patients presenting with unexplained central nervous system symptoms.
Mycobacterium avium complex infection-related immune reconstitution inflammatory syndrome of the central nervous system in an HIV-infected patient: case report and review.
Lee Yi-Chien,Lu Ching-Lan,Lai Chung-Chih,Tseng Yu-Tzu,Sun Hsin-Yun,Hung Chien-Ching
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
Disseminated Mycobacterium avium complex (MAC) infection involves the central nervous system (CNS) less frequently than tuberculosis, and MAC-related immune reconstitution inflammatory syndrome (IRIS) of the CNS in AIDS patients is even more rarely described. We report a case of MAC-related IRIS of the CNS in an HIV-infected patient who presented with meningoencephalitis and myelitis 2 months after discontinuation of antiMAC therapy, when he had achieved prolonged suppression of HIV replication and restoration of CD4 counts to >100 cells/μL for 1 year. Cases of MAC-related IRIS of the CNS reported in the literature are reviewed.
Mycobacterium fortuitum infection of ventriculoperitoneal shunt.
Midani S,Rathore M H
Southern medical journal
Mycobacterium fortuitum is one of the rapidly growing mycobacteria found in soil, dust, and water. It can be isolated as a normal colonizing organism, but as a pathogen this organism causes mainly skin and soft tissue infection preceded by trauma. A wide variety of infections can occur in individuals with predisposing conditions. Central nervous system infection with M fortuitum is rare, and meningitis occurs after surgery or trauma. We believe that ventriculoperitoneal (VP) shunt infection with this organism has not been reported in the literature. Practitioners should be aware of this rare entity and should suspect it in the presence of cerebrospinal fluid pleocytosis with sterile culture, and after trauma, surgery, or manipulation of the VP shunt hardware. Mycobacterium fortuitum is resistant to most first-line and second-line antituberculous drugs, and treatment should include surgical debridement in addition to prolonged antimicrobial therapy.
Occurrence of overlooked zoonotic tuberculosis: detection of Mycobacterium bovis in human cerebrospinal fluid.
Shah N P,Singhal A,Jain A,Kumar P,Uppal S S,Srivatsava M V P,Prasad H K
Journal of clinical microbiology
The paucibacillary nature of the cerebrospinal fluid (CSF) has been a major obstacle in the diagnosis of human tuberculous meningitis (TBM). This study shows that with molecular techniques direct precise determination to the species level of mycobacterial pathogens can be made. The present report describes the utility of a nested PCR (N-PCR) assay (A. Mishra, A. Singhal, D. S. Chauhan, V. M. Katoch, K. Srivastava, S. S. Thakral, S. S. Bharadwaj, V. Sreenivas, and H. K. Prasad, J. Clin. Microbiol. 43:5670-5678, 2005) in detecting M. tuberculosis and M. bovis in human CSF. In 2.8% (6/212) of the samples, M. tuberculosis was detected, and in 17% (36/212), M. bovis was detected. Mixed infection was observed in 22 samples. Comparative analysis of clinical diagnosis, smear microscopy, and N-PCR in 69 patients (TBM, 25; non-TBM, 44) showed that the sensitivity of N-PCR (61.5%) was greater than that of smear microscopy (38.4%). Determination to the species level is important from the viewpoint of determining the prevalence of these mycobacteria in a community and would influence strategies currently adopted for the prevention of tuberculosis.
A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer.
Eddyani Miriam,Vandelannoote Koen,Meehan Conor J,Bhuju Sabin,Porter Jessica L,Aguiar Julia,Seemann Torsten,Jarek Michael,Singh Mahavir,Portaels Françoise,Stinear Timothy P,de Jong Bouke C
PLoS neglected tropical diseases
BACKGROUND:Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes. METHODOLOGY:We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin. PRINCIPAL FINDINGS:The findings suggest that after surgical treatment-without antibiotics-the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse. CONCLUSIONS:To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.
Whole genome sequencing of Nontuberculous Mycobacterium (NTM) isolates from sputum specimens of co-habiting patients with NTM pulmonary disease and NTM isolates from their environment.
Yoon Jung-Ki,Kim Taek Soo,Kim Jong-Il,Yim Jae-Joon
BACKGROUND:Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. RESULTS:We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients' NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources. CONCLUSIONS:In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.
Comprehensive Determination of and From Targeted Capture Sequencing.
He Ya,Gong Ziying,Zhao Xiaokai,Zhang Daoyun,Zhang Zhongshun
Frontiers in cellular and infection microbiology
Infection of (MTB) and (NTM) challenges effective pulmonary infectious disease control. Current phenotypic and molecular assays could not comprehensively and accurately diagnose MTB, NTM, and drug resistance. Next-generation sequencing allows an "all-in-one" approach providing results on expected drug susceptibility testing (DST) and the genotype of NTM strains. In this study, targeted capture sequencing was used to analyze the genetic backgrounds of 4 MTB strains and 32 NTM pathogenic strains in 30 clinical samples, including 14 sputum specimens and 16 bronchoalveolar lavage fluid samples. Through comparing with other TB diagnostic tests, we proved that targeted capture sequencing could be used as a highly sensitive (91.3%) and accurate (83.3%) method to diagnose TB, as well as MGIT 960. Also, we identified 7 NTM strains in 11 patients; among them, seven patients were MTB/NTM co-affected, which indicated that it was a meaningful tool for the diagnosis and treatment of NTM infection diseases in clinic. However, based on a drug-resistant mutation library (1,325 drug resistance loci), only 9 drug resistance strains and 22 drug resistance loci were discovered, having considerable discordance with the drug-resistant results of MGIT 960. Our finding indicated that targeted capture sequencing approach was applicable for the comprehensive and accurate diagnosis of MTB and NTM. However, from data presented here, the DST results identified by next-generation sequencing (NGS) showed a relatively low consistency with MGIT 960, especially in sputum samples. Further work should be done to explore the reasons for low drug-resistance detection rate of NGS.
Genomic characterization of Nontuberculous Mycobacteria.
Fedrizzi Tarcisio,Meehan Conor J,Grottola Antonella,Giacobazzi Elisabetta,Fregni Serpini Giulia,Tagliazucchi Sara,Fabio Anna,Bettua Clotilde,Bertorelli Roberto,De Sanctis Veronica,Rumpianesi Fabio,Pecorari Monica,Jousson Olivier,Tortoli Enrico,Segata Nicola
Mycobacterium tuberculosis and Mycobacterium leprae have remained, for many years, the primary species of the genus Mycobacterium of clinical and microbiological interest. The other members of the genus, referred to as nontuberculous mycobacteria (NTM), have long been underinvestigated. In the last decades, however, the number of reports linking various NTM species with human diseases has steadily increased and treatment difficulties have emerged. Despite the availability of whole genome sequencing technologies, limited effort has been devoted to the genetic characterization of NTM species. As a consequence, the taxonomic and phylogenetic structure of the genus remains unsettled and genomic information is lacking to support the identification of these organisms in a clinical setting. In this work, we widen the knowledge of NTMs by reconstructing and analyzing the genomes of 41 previously uncharacterized NTM species. We provide the first comprehensive characterization of the genomic diversity of NTMs and open new venues for the clinical identification of opportunistic pathogens from this genus.
Unusual cause of progressively impaired cognitive function: complex meningoencephalitis.
Okazaki Yuji,Higashi Yusuke
BMJ case reports
complex (MAC) is a rare cause of meningoencephalitis. Non-tuberculous mycobacterium meningoencephalitis including MAC meningoencephalitis is an important cause of rapidly progressive dementia. We present a case of MAC meningoencephalitis in an immunosuppressed woman who had progressively impaired cognitive function. An 83-year-old woman who had been taking glucocorticoid for myasthenia gravis developed cognitive dysfunction and visual hallucinations over a period of 2 weeks. Cerebrospinal fluid (CSF) findings were normal, but MAC was positive in CSF culture and and were identified by PCR. She was treated with multiple antimycobacterial agents and her symptoms fully recovered. MAC meningoencephalitis is an unusual cause of progressively impaired cognitive function. The possibility of mycobacterial central nervous system infection cannot be excluded by normal CSF findings.
Mycobacterium fortuitum meningitis associated with an epidural catheter: case report and a review of the literature.
Madaras-Kelly K J,DeMasters T A,Stevens D L
Mycobacterium fortuitum is a rapidly growing organism that has rarely been associated with meningitis. A patient developed M. fortuitum meningitis as the result of a permanent indwelling, contaminated, epidural catheter. Diagnosis and treatment of the disease are difficult in that clinical features may be indolent, and many antimicrobials with activity against M. fortuitum have minimal cerebrospinal fluid penetration. This patient was cured with an antibiotic regimen that consisted of doxycycline, ciprofloxacin, imipenem, and clarithromycin, and removal of the epidural catheter.
Successful treatment of atypical mycobacterial meningitis by fluoroquinolone.
Komachi H,Uchihara T,Saito Y,Takewaki S,Nagai R,Furukawa T
Journal of the neurological sciences
We report a case of restricted meningeal infection by atypical mycobacteria, identified by the polymerase chain reaction, in a non-immunocompromised adult successfully treated by multiple antibiotics including fluoroquinolone. New quinolones should be considered as a therapeutic option for such mycobacterial meningitis.
Mycobacterium fortuitum endocarditis and meningitis after balloon mitral valvotomy.
Kuruvila M T,Mathews P,Jesudason M,Ganesh A
The Journal of the Association of Physicians of India
Mycobacteria rarely cause endocardial infections. We describe the clinical course of a patient who developed endocarditis, and meningitis with Mycobacterium fortuitum following balloon mitral valvotomy. The patient was treated with amikacin and clarithromycin but did not respond. She developed haemolytic anaemia as the terminal event.
Pathogenesis, diagnosis, treatment, and outcome aspects of cerebral tuberculosis.
Katti Muralidhar K
Medical science monitor : international medical journal of experimental and clinical research
Cerebral tuberculosis or tuberculosis of the brain manifests predominantly as tuberculous meningitis followed by tuberculoma, tuberculous abscess, and other concomitant forms such as cerebral miliary tuberculosis, tuberculous encephalopathy, tuberculous encephalitis, and tuberculous arteritis. Different forms of cerebral tuberculosis are mainly caused by Mycobacterium tuberculosis and also by non-tuberculous mycobacteria such as M. avium-intracellulare in human immunodeficiency virus-infected persons. Cerebral tuberculosis is diagnosed based on clinical features, cerebrospinal fluid studies combined with radiological images. Early diagnosis, prompt institution of anti-tubercular treatment, and the clinical stage at which the patient presents are important and deciding factors for final outcome. The present review highlights the pathogenesis, recent strides made in diagnosis, including sensitive and specific molecular diagnostic (immunologic and polymerase chain reaction) tests, treatment, and outcome aspects of cerebral tuberculosis.
Isolated pituitary granuloma by atypical Mycobacterium in a nonimmunosuppressed woman.
Florakis Dimos,Kontogeorgos George,Anapliotou Margarita,Mazarakis Nikos,Richter Elvira,Brück Wolfgang,Piaditis George
A 32-year-old woman presented with a 10-day history of fever (38.0 degrees C), headaches, nausea, vomiting and a 6-month history of diabetes insipidus and amenorrhoea. Two months previously she had undergone a surgical drilling of the right mastoid area because of mastoiditis. Endocrine investigation showed elevated serum prolactin levels, secondary adrenal and gonadal failure and a normal thyroid function. Cranial MRI scan revealed a contrast enhancing intrasellar mass (approximately 2 cm) of heterogeneous appearance with suprasellar extension and thickening of the pituitary stalk. Lumbar puncture was suggestive of aseptic meningitis. The Ziehl-Neelsen stain of cerebrospinal fluid (CSF) and the tuberculin skin test were both negative. The pituitary mass was removed with a transsphenoidal approach. Histological examination demonstrated destruction of the adenohypophysis by epithelioid granulomas with partial caseous necrosis and microabscess formation, suggestive of a mycobacterial infection. A polymerase chain reaction analysis performed on paraffin-embedded tissue was positive for mycobacterial DNA. According to the individual 16S sequence, it was identified as Mycobacterium malmoense, an atypical nontuberculous mycobacterium (NTM). In conclusion, this is the first case of an isolated pituitary granuloma caused by an NTM infection in a nonimmunosuppressed patient.
Nontuberculous mycobacterial infection of the central nervous system in patients with AIDS.
Jacob C N,Henein S S,Heurich A E,Kamholz S
Southern medical journal
Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases. Of these, 15 were caused by Mycobacterium avium-intracellular (MAI), and one was caused by M fortuitum. All patients with MAI infection had widespread dissemination and at least one risk factor for AIDS. Clinical features included weight loss, altered mentation, and seizures. Analysis of cerebrospinal fluid revealed a mildly elevated leukocyte count with lymphocyte predominance and normal protein and glucose values. All direct smears were negative for acid-fast bacilli. In-hospital mortality was 67%. The patient with infection due to M fortuitum had a preexisting diagnosis of AIDS and had a right upper lobe pneumonia and headaches. Cranial CT showed an enlarged infundibulum of the pituitary gland. Results of CSF analysis were essentially normal, and direct smears were negative. He left the hospital against medical advice. Our study indicates that the finding of MAI in the CSF in patients with AIDS is associated with an in-house mortality of 67% indicating a very poor prognosis.
Nontuberculous mycobacterial meningitis: report of two cases and review.
Flor A,Capdevila J A,Martin N,Gavaldà J,Pahissa A
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Nontuberculous mycobacterial meningitis (NTMM) is still a rare disease despite the increase in the number of cases of disseminated mycobacterial infection related to the AIDS epidemic. Moreover, there are doubts as to the clinical relevance of the isolation of mycobacteria other than Mycobacterium tuberculosis from cerebrospinal fluid. After analyzing the clinical and pathological data, we classified the cases of NTMM into three groups: definitive (28 cases), probable (19), and doubtful (5). We found that Mycobacterium avium is the most commonly isolated species (60% of cases). M. avium meningitis presents as a disseminated disease, is usually related to serious underlying conditions (mainly immunosuppression), and is associated with a death rate that approaches 70%. Mycobacterium fortuitum meningitis is associated with previous neurosurgery or back trauma; the prognosis for this infection is better when the concomitant abscesses are drained. The clinical characteristics of Mycobacterium kansasii meningitis are similar to those of M. tuberculosis meningitis, but the mortality related to M. kansasii meningitis is high despite appropriate antibiotic treatment. Herein, we present two cases of NTMM that occurred at our center, and we review 50 additional cases reported in the English-language literature.
[A case of Mycobacterium fortuitum meningitis following surgery for meningioma].
Fujikawa Keita,Suenaga Akihito,Motomura Masakatsu,Fukuda Taku,Ooe Nobuharu,Eguchi Katsumi
Rinsho shinkeigaku = Clinical neurology
A 57-year-old woman had undergone surgery for meningioma. After the surgery, she suffered from repeated fever and headache. One year after surgery, she was admitted to our hospital for further examination. Cerebro-spinal fluid (CSF) findings indicated bacterial meningitis infection. Germ culture, acid-fast bacterium culture, PCR for mycobacteriosis and cryptococcus antigens as well as cytological examination of CSF were checked repeatedly. However, all examinations were negative and etiology was unknown. We treated with many anti-bacterial, anti-fungal and anti-tubercular drugs, but CSF findings were not improved. We repeated CSF examination and finally Mycobacterium fortuitum (M. fortuitum) was isolated. Clarithromycin (CAM) was started for M. fortuitum meningitis. After drug sensitivity testing, levofloxacin (LVFX), which was effective against M. fortuitum, was added to CAM, after which clinical and CSF findings improved dramatically. M. fortuitum rarely causes CNS infection. Several English literatures on M. fortuitum meningitis after traumatic injury and surgery have been published. Its CSF findings distinctly resemble those of bacterial meningitis, but are resistant to the usual antituberculosis drugs. We reported a case of M. fortuitum meningitis associated with surgery for meningioma.
Incidental intraoperative diagnosis of Mycobacterium abscessus meningeal infection: a case report and review of the literature.
Giovannenze Francesca,Stifano Vito,Scoppettuolo Giancarlo,Damiano Fernando,Pallavicini Federico,Delogu Giovanni,Palucci Ivana,Rapisarda Alessandro,Sturdà Cosimo,Pompucci Angelo
PURPOSE:Mycobacterium abscessus, and rapidly growing mycobacteria in general, are rare but increasing causes of central nervous system (CNS) infections. The aim of this study is to highlight the importance of considering these microorganism in the differential diagnosis of CNS infections, obtaining a prompt diagnosis, and improving clinical outcomes. METHODS:Case report and literature review. RESULTS:We report a case of meningeal infection in a patient who underwent decompressive craniectomy after a craniofacial trauma. The diagnosis was made analyzing a sample obtained during a second operation of cranioplasty. A regimen of amikacin, clarithromycin, and imipenem/cilastatin was started. In the following days, the patient experienced a variety of side effects. So, first clarithromycin was replaced with linezolid, then amikacin was stopped and cefoxitin added to the therapy and at the end all the antibiotics were withdrawn. The patient was discharged in good conditions and a clinical interdisciplinary follow-up was started. After 12 months, the patient is still doing well. After a literature analysis, 15 cases of M. abscessus CNS infections were identified. Various modes of acquisition, underlying disease and therapeutic schemes were evident. CONCLUSIONS:Considering the results of the literature analysis and the increasing incidence of M. abscessus, all specialists involved in the management of CNS infection should be aware of the importance of atypical microorganisms in differential diagnosis.
Acute disseminated encephalomyelitis associated with meningitis due to Mycobacterium intracellulare.
Okada Hiroshi,Yoshioka Keiji
Internal medicine (Tokyo, Japan)
A 73-year-old woman was admitted to our hospital because of persistent fever, headache and fatigue for several weeks. On admission, she was diagnosed as having meningitis due to Mycobacterium intracellulare (M. intracellulare) detected in her cerebrospinal fluid (CSF) by polymerase chain reaction. Even though anti-tuberculous therapy improved her CSF findings, her condition was not restored. Brain MRI showed multifocal and asymmetrical increases in T2 signals involving white matter and cortical gray-white junction of cerebral hemispheres, cerebellum and brainstem. Based on the progression of clinical symptoms and radiological features, we diagnosed her illness as acute disseminated encephalomyelitis (ADEM) associated with meningitis due to M. intracellulare. Steroid therapy dramatically improved her condition. This is the first report of ADEM following meningitis due to M. intracellulare in a non-immunocompromized host.
Polymicrobial Intracerebral Abscess Growing Mycobacterium avium Complex and Achromobacter xylosoxidans: Case Report and Literature Review.
Rotter Juliana,Graffeo Christopher S,Perry Avital,Gilder Hannah E,Wilson John W,Link Michael J
BACKGROUND:Mycobacterium avium complex (MAC) and Achromobacter xylosoxidans (AX) are uncommon sources of neurosurgical infections, particularly in immunocompetent hosts. We report the first published case of intracranial AX abscess and polymicrobial AX-MAC abscess, as well as the fourth MAC abscess in a non-immunocompromised patient. METHODS:This case report was conducted via retrospective chart review. A literature review was completed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS:Ten years following mucocele resection, a 60-year-old man presented with sinus congestion and headache. Head imaging revealed a left frontal lesion abutting the cribriform plate and ethmoid roof. The patient had a left frontal craniotomy for abscess drainage. Intraoperative cultures demonstrated polymicrobial growth of AX and MAC, managed with antimicrobial therapy and staged skull base reconstruction. Three cases of MAC abscess and 16 cases of AX ventriculitis or meningitis have been reported in immunocompetent patients. All MAC cerebral abscesses occurred in adults, one of whom succumbed to the infection. Of the 9 AX meningitis cases, 4 occurred in neonates and 2 in pediatric patients. Six of the 7 AX ventriculitis cases occurred after neurosurgical operations at the same hospital from contaminated chlorhexidine basins. Except for the neonates, AX ventriculitis or meningitis patients had undergone neurosurgery or had a history of cranial trauma. There were no reports of polymicrobial AX-MAC intracranial abscess. CONCLUSIONS:AX and MAC are rare causes of intracranial infection. Patients with these pathogens identified in the central nervous system require a multidisciplinary approach for successful management.
Indole Propionic Acid, an Unusual Antibiotic Produced by the Gut Microbiota, With Anti-inflammatory and Antioxidant Properties.
Negatu Dereje Abate,Gengenbacher Martin,Dartois Véronique,Dick Thomas
Frontiers in microbiology
Most antibiotics are produced by soil microbes and typically interfere with macromolecular synthesis processes as their antibacterial mechanism of action. These natural products are often large and suffer from poor chemical tractability. Here, we discuss discovery, mechanism of action, and the therapeutic potentials of an unusual antibiotic, indole propionic acid (IPA). IPA is produced by the human gut microbiota. The molecule is small, chemically tractable, and targets amino acid biosynthesis. IPA is active against a broad spectrum of mycobacteria, including drug resistant and non-tuberculous mycobacteria (NTM). Interestingly, the microbiota-produced metabolite is detectable in the serum of healthy individuals, tuberculosis (TB) patients, and several animal models. Thus, the microbiota in our gut may influence susceptibility to mycobacterial diseases. If a gut-lung microbiome axis can be demonstrated, IPA may have potential as a biomarker of disease progression, and development of microbiota-based therapies could be explored. In addition to its antimycobacterial activity, the molecule displays anti-inflammatory and antioxidant properties. This raises the possibility that IPA has therapeutic potential as both antibiotic and add-on host-directed drug for the treatment of TB in patient populations where disease morbidity and mortality is driven by excessive inflammation and tissue damage, such as TB-associated immune reconstitution inflammatory syndrome, TB-meningitis, and TB-diabetes.
Fatal Disseminated Mycobacterium chelonae Infection in an Immunocompromised Host--A Unique Presentation.
Mankad Sanket,Karthik Rajiv,Rupali Priscilla,Michael Joy S
The Journal of the Association of Physicians of India
Disseminated disease due to rapidly growing non tuberculous mycobacteria especially in the immunocompromised host is being increasingly reported. The usual manifestations of disease being skin and soft tissue infection, post operative wound infection and pulmonary disease. We present a case of a disseminated infection due to Mycobacterium chelonae with features of chronic meningitis and knee joint arthritis in a patient with systemic lupus erythematosus on systemic steroids and mycophenolate. M chelonae was isolated from both synovial and cerebrospinal fluid and anti microbial therapy was initiated as per sensitivity results. However the patient's clinical condition continued to worsen and she succumbed to her illness.
Chronic mycobacterial meningitis due to Mycobacterium chelonae: a case report.
Salmanzadeh Shokrallah,Honarvar Negin,Goodarzi Hamed,Khosravi Azar Dokht,Nashibi Roohangiz,Serajian Amir Arsalan,Hashemzadeh Mohammad
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
We report a case of chronic meningitis due to Mycobacterium chelonae. This organism is a rapidly growing Mycobacterium (RGM) and can be found worldwide in environmental sources such as soil, dust, and water. M. chelonae is an uncommon cause of meningitis; the majority of infections caused by this organism are localized cutaneous or soft tissue infections, and rarely lung infections. The organism is indistinguishable phenotypically, so we applied PCR based on the rpoB gene sequence followed by restriction fragment length polymorphism (RFLP) for molecular identification. The subsequent sequencing of RFLP products revealed 99.7% similarity with M. chelonae.
Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies.
Liew Woei-Kang,Thoon Koh-Cheng,Chong Chia-Yin,Tan Natalie W H,Cheng Duo-Tong,Chan Bianca S W,Ng Michelle S Y,Das Lena,Arkachaisri Thaschawee,Huang Chiung-Hui,Kuan Jyn-Ling,Chai Louis Y A,Koh Mark Jean Aan
Journal of clinical immunology
Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome-like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.
Nontuberculous mycobacterial infections in King Chulalongkorn Memorial Hospital.
Saritsiri Suthee,Udomsantisook Nibhondh,Suankratay Chusana
Journal of the Medical Association of Thailand = Chotmaihet thangphaet
BACKGROUND:Nontuberculous mycobacteria (NTM) can cause infections in both human immunodeficiency virus (HIV)-infected and HIV-noninfected patients. The incidence of NTM infections has been increasing since the acquired immunodeficiency syndrome (AIDS) epidemics. However, the epidemiologic and clinical data of NTM infections in Thailand are limited. OBJECTIVE:Determine the epidemiology, clinical manifestations, treatment, and outcome of NTM infections in King Chulalongkorn Memorial Hospital from January 2000 to December 2003. MATERIAL AND METHOD:One hundred and fourteen patients had positive NTM cultures; however, complete medical records were available in only 103 (90.3%) patients. RESULTS:There were 71 (68.9%) HIV-infected patients, and 38 (87%) of them had the CD4 counts of < 200 cells/microL (range 4-360). Among HIV-infected patients, the most common previous opportunistic infections included tuberculosis (36.6%), Pneumocystis jirovecii pneumonia (25.3%), cryptococcal meningitis (15.5%), penicilliosis (5.6%), and cytomegalovirus infection (5.6%). Most patients presented with prolonged fever (67%), chronic cough (54.4%), lymphadenopathy (52.4%), weight loss (50.5%), or chronic diarrhea (31%). The clinical manifestations included disseminated (17.4%) and localized (82.6%) infections. The localized infection included pulmonary infection (82.3%), followed by gastrointestinal infection (34.1%), skin infection (12.9%), lymphadenitis (8.2%), genitourinary tract infection (2.4%), central nervous system infection (2.4%), and keratitis (1.2%). Mycobacterium avium complex (MAC) was the predominant species (48.5%), followed by M. kansasii (19.4%), and rapidly growing mycobacteria (16.4%). Diffuse reticular infiltration was most commonly observed on chest radiography (53.4%). Abnormal laboratory findings included anemia (48.5%), hyponatremia (42.7%), and elevated alkaline phosphatase (39.8%). The overall mortality rate was 34.8% (45.9% and 11.1% in HIV- and HIV-noninfected patients). CONCLUSION:A diagnosis of NTM infection requires a high index of suspicion in patients especially with AIDS or immunocompromised status who present with prolonged fever, with or without organ-specific symptoms and signs. Therefore, clinical specimens must be sent for mycobacterial cultures for a definite diagnosis, a determination of the species of NTM, and an appropriate management. In addition to four standard antituberculous drugs, clarithromycin should be added for the treatment of MAC in patients with AIDS who presented with disseminated opportunistic infections before obtaining the microbiologic results.
CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates.
Lee Meng-Rui,Cheng Aristine,Lee Yi-Chieh,Yang Ching-Yao,Lai Chih-Cheng,Huang Yu-Tsung,Ho Chao-Chi,Wang Hao-Chien,Yu Chong-Jen,Hsueh Po-Ren
The Journal of antimicrobial chemotherapy
OBJECTIVES:CNS infections caused by non-tuberculous mycobacteria (NTM) are rare and only three cases of CNS infections due to Mycobacterium abscessus complex have been reported. METHODS:We searched the Mycobacteriology Database of the National Taiwan University Hospital and identified patients with CNS infections due to NTM. RESULTS:A total of 15 patients, namely 4 HIV-seropositive patients and 11 HIV-seronegative patients, with CNS infections caused by NTM were identified during 2000-10. All of the HIV-seropositive patients had disseminated Mycobacterium avium complex infections. Among the 11 HIV-seronegative patients, NTM CNS infections were due to M. abscessus complex in 8 patients, M. avium complex in 2 patients and Mycobacterium kansasii in 1 patient. All the six preserved M. abscessus complex isolates were confirmed to be Mycobacterium massiliense by erm(41) PCR and 23S rRNA gene sequence analysis. Among the eight patients with infections due to M. abscessus complex, three had otolaryngological diseases, four had received neurosurgery and one had disseminated disease. Five patients received surgical debridement or intracranial device removal and three patients died of M. abscessus complex CNS infection. Among the five patients who survived, all received clarithromycin-based combination therapy with a median duration of 12 months and four received surgical intervention. All six isolates available for drug susceptibility testing showed uniform susceptibility to clarithromycin and five were susceptible to amikacin. CONCLUSIONS:Our study revealed that M. abscessus complex isolates, particularly M. massiliense, should be considered potential pathogens causing CNS infections. Long-duration clarithromycin-based combination therapy plus surgical intervention may provide the best chance of cure.
Central nervous system infection with non-tuberculous mycobacteria: a report of that infection in two patients with AIDS.
Cai Rentian,Qi Tangkai,Lu Hongzhou
Drug discoveries & therapeutics
Meningitis caused by non-tuberculous mycobacteria (NTM) has a low incidence and is a rare form of NTM infection. In an increasing number of cases, however, disseminated mycobacterial infection is noted in acquired immune deficiency syndrome (AIDS). Described here are two patients with AIDS who were infected with NTM. Both patients eventually died, but one did receive anti-NTM treatment. Non-tuberculous mycobacterial meningitis must be suspected in patients with AIDS who present with prolonged fever and brain symptoms, and anti-NTM drugs should be promptly administered if necessary.
Successful treatment of meningoencephalitis caused by Mycobacterium avium intracellulare in AIDS.
Malessa R,Diener H C,Olbricht T,Böhmer B,Brockmeyer N H
The Clinical investigator
A wide variety of pathologies afflicting the CNS is see in patients infected with the human immunodeficiency virus. We report the case of relapsing meningoencephalitis caused by Mycobacterium avium intracellulare (MAI) in a homosexual male with the acquired immunodeficiency syndrome in whom repeated use of polymerase chain reaction was required to detect MAI-specific DNA in the cerebrospinal fluid. Successful responses to early empirical antibiotic combination treatment, including the drugs clarithromycin and rifabutin, were demonstrated by clinical, EEG, and CSF improvement during an 8-month period. To our knowledge, this study presents the first known patient with the acquired immunodeficiency syndrome effectively treated for MAI meningoencephalitis and suggests that modern antimycobacterial combination therapy may improve the poor prognosis of CNS infections with nontuberculous mycobacteria.
Discontinuation of secondary prophylaxis against disseminated Mycobacterium avium complex infection and toxoplasmic encephalitis.
Zeller Valérie,Truffot Chantal,Agher Rachid,Bossi Philippe,Tubiana Roland,Caumes Eric,Jouan Marc,Bricaire François,Katlama Christine
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
We retrospectively studied outcomes for patients infected with human immunodeficiency virus who received highly active antiretroviral therapy (HAART) and had stopped receiving secondary prophylaxis against toxoplasmic encephalitis (TE) or disseminated Mycobacterium avium complex (MAC) infection. Nineteen patients had a history of TE, and 26 had a history of disseminated MAC infection. The median duration of secondary prophylaxis was 27 months, and the median duration of HAART before discontinuation of secondary prophylaxis was 22 months. Median CD4(+) cell counts at the time of cessation of secondary prophylaxis against TE or disseminated MAC infection were 404 and 105 cells/mm(3), respectively. Plasma virus load was undetectable in 68% of the patients who had a history of TE and in 31% of patients who had a history of disseminated MAC infection. Patients were followed up for a median of 29 months after discontinuation of secondary prophylaxis; no relapses occurred in patients with a history of TE, and 3 relapses occurred in patients with a history of disseminated MAC infection (incidence, 4 relapses per 100 person-years).
Invasion of the brain and chronic central nervous system infection after systemic Mycobacterium avium complex infection in mice.
Wu H S,Kolonoski P,Chang Y Y,Bermudez L E
Infection and immunity
Central nervous system (CNS) infections caused by nontuberculous mycobacteria have been described previously, especially in patients with AIDS. To investigate specific aspects of the pathogenesis of this entity, C57BL bg(+)/bg(-) mice were infected intravenously with Mycobacterium avium, and cultures of blood and brain as well as histopathology examination of brain tissue were carried out at several time points up to 6 months after infection. Low-grade inflammatory changes with small aggregates of lymphocytes and macrophages as well as perivascular cuffing were seen early in the infection. A small number of bacteria could be observed in the parenchyma of the choroid plexus. Six months after infection, numerous bacteria were present within the foamy macrophage of the granulomatous lesions along the ventricle and meninges. None of the mice developed clinical signs of meningitis or encephalitis or even died spontaneously during the period of observation. Use of CD18(-/-) knockout mice indicated that transport of the bacterium within neutrophils or monocytes into the brain is unlikely. Mild chronic CNS infection developed in the mice during sustained systemic M. avium infection, similar to what has been reported in most human cases.
[Multiple infectious intracranial lesions of Mycobacterium genavense in an immunocompromised patient].
Uchino Haruto,Terasaka Shunsuke,Yamaguchi Shigeru,Kobayashi Hiroyuki,Kawai Kagari,Kubota Kanako,Ooe Shinji,Houkin Kiyohiro
Brain and nerve = Shinkei kenkyu no shinpo
Nontuberculous mycobacteria rarely infect the central nervous system. Recently, Mycobacterium genavense, nontuberculous mycobacterium (NTM), has been identified as a significant pathogen in patients. In this report, we describe multiple intracranial lesions caused by M. genavense in an immunocompromised host. A 50-year-old man presented with dysarthria, aphasia, and right hemiparesis. He had a primary immunodeficiency and a M. genavense infection in the thoracic and abdominal lymph nodes. Magnetic resonance imaging revealed multiple intracranial masses in the subcortical regions with extensive perifocal edema. Laboratory investigations and cultures of cerebrospinal fluid provided no evidence of disseminated infection. We obtained a biopsy sample via a small craniotomy using neuronavigation, and NTM infection was confirmed on analysis of the specimen. He was treated with antimycobacterial agents, and the clinical symptoms and radiological findings improved. Although a surgical procedure bears the potential risk of infection, especially in an immunocompromised patient, a brain biopsy was necessary for definitive diagnosis in this case and it aided in the administration of appropriate treatment.
Skin nontuberculous mycobacterial infection in systemic lupus erythematosus: an unusual skin infection mimicking lupus vasculitis.
Touma Zahi,Haddad Amir,Gladman Dafna D,Uleryk Elizabeth M,Urowitz Murray B
Seminars in arthritis and rheumatism
OBJECTIVES:To report 2 cases of skin nontuberculous mycobacteria (NTM) occurring in lupus patients and to systematically review the medical literature addressing skin NTM in lupus. METHODS:We reported 2 cases of skin NTM in lupus patients followed at the Toronto Lupus Clinic. We conducted a systematic review of the literature on NTM in lupus patients. Ovid Medline (1946 to March 12, 2012) and Embase (1980 to March 12, 2012) were searched for relevant publications. RESULTS:Of the 1356 retrieved abstracts, 19 publications were identified and 25 cases of skin NTM were extracted. Skin presentations in this review ranged from papules, plaques, and nodules to ulcerative lesions and abscesses. Skin lesions occurred in the setting of active and inactive lupus and while patients were maintained on steroids and sometimes immunosuppressants. The pathogen species included Mycobacterium chelonae, Mycobacterium haemophilum, Mycobacterium kansasii, Mycobacterium avium, Mycobacterium scrofulaceum, Mycobacterium fortuitum, Mycobacterium marinatum, and Mycobacterium szulgai. The duration of antimycobacterial drugs ranged from 3 to 12 months. Skin excision, drainage, and debridement might be required in some cases. Empirical monotherapy was used initially, and the final choice of antibiotics was based on the susceptibility determined in culture. Overall, the outcomes of the skin lesions resulted in either complete recovery or improvement. CONCLUSIONS:A high index of suspicion in lupus patients is required to diagnose NTM, as the initial presentation of NTM can mimic lupus skin manifestations.
Mycobacterium chimaera Encephalitis Following Cardiac Surgery: A New Syndrome.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
We report the cases of 3 patients with fatal, disseminated Mycobacterium chimaera infections following cardiac surgeries. Progressive neurocognitive decline and death were explained by active granulomatous encephalitis, with widespread involvement of other organs. This syndrome is clinically elusive and, thus, may have caused deaths in prior reported series.
Ventriculoperitoneal Shunt Infection with Mycobacterium abscessus: A Rare Cause of Ventriculitis.
Levy Zachary D,Du Victor,Chiluwal Amrit,Chalif David J,Ledoux David E
BACKGROUND:Mycobacterium abscessus is a rapidly growing atypical mycobacterium implicated in chronic lung disease, otitis media, surgical site infections, and disseminated cutaneous diseases. It is typically seen in patients with some degree of immunosuppression. Only 1 previous case has been reported in the setting of ventriculoperitoneal (VP) shunt infection. We report a case of M abscessus as the causative organism in a VP shunt infection in an immunocompetent adult. CASE DESCRIPTION:A 67-year-old woman required VP shunt placement after aneurysmal subarachnoid hemorrhage complicated by hydrocephalus. Her course was complicated by repeat hospitalization for 2 shunt infections, the second of which did not respond to standard antibiotic therapy. Cultures repeatedly grew M abscessus. The patient continued to decline and eventually died after transfer to the palliative care service. CONCLUSIONS:Nontuberculous mycobacteria are rare, atypical organisms in the setting of VP shunt infection. Patients with ventriculitis secondary to atypical mycobacteria may exhibit drug-resistant cerebrospinal fluid pleocytosis in the face of standard antibiotic regimens.