scholarly journals Pott's Disease? AIDS-Associated Mycobacterium heckeshornense Spinal Osteomyelitis and Diskitis

2014 ◽  
Vol 53 (2) ◽  
pp. 716-718 ◽  
Author(s):  
Robert J. Carpenter ◽  
Paul C. F. Graf
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Acid Fast Bacillus ◽  
Review Of The Literature ◽  
Content Type ◽  
Pott’S Disease ◽  
Adequate Therapy ◽  
Spinal Osteomyelitis

Acid-fast bacillus (AFB) spinal osteomyelitis in a patient with AIDS is often presumed to be caused by reactivatedMycobacterium tuberculosis. However, other AFB pathogens can mimicM. tuberculosisand, to ensure appropriate and adequate therapy, should be considered by clinicians. We present a case of aggressive spinal osteomyelitis caused byMycobacterium heckeshornensein an AIDS patient; a review of the literature is also included.

scholarly journals Epidemiologic Correlates of Pyrazinamide-Resistant Mycobacterium tuberculosis in New York City

2015 ◽  
Vol 59 (10) ◽  
pp. 6140-6150 ◽  
Author(s):  
Dawn Verdugo ◽  
Dorothy Fallows ◽  
Shama Ahuja ◽  
Neil Schluger ◽  
Barry Kreiswirth ◽  
...  
Keyword(s):  
Risk Factors ◽  
New York ◽  
New York City ◽  
Mycobacterium Tuberculosis ◽  
York City ◽  
Clinical Information ◽  
Drug Susceptibility ◽  
Acid Fast Bacillus ◽  
Drug Susceptibility Testing ◽  
Content Type

ABSTRACTPyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors, and molecular epidemiology associated with PZA-resistant (PZAr)Mycobacterium tuberculosisin New York City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by the NYC Department of Health and Mental Hygiene (DOHMH) were genotyped by IS6110-based restriction fragment length polymorphism and spoligotype. Multidrug-resistant (MDR) isolates underwent DNA sequencing of resistance-determining regions ofpncA,rpoB,katG, andfabG1. Demographic and clinical information were extracted from the NYC DOHMH TB registry. During this period, PZArdoubled (1.6% to 3.6%) overall, accounting for 44% (70/159) of the MDR population and 1.4% (75/5511) of the non-MDR population. Molecular genotyping revealed strong microbial phylogenetic associations with PZAr. Clustered isolates and those from acid-fast bacillus (AFB) smear-positive cases had 2.7 (95% confidence interval [CI] = 1.71 to 4.36) and 2.0 (95% CI = 1.19 to 3.43) times higher odds of being PZAr, respectively, indicating a strong likelihood of recent transmission. Among the MDR population, PZArwas acquired somewhat more frequently via primary transmission than by independent pathways. Our molecular analysis also revealed that several historicM. tuberculosisstrains responsible for MDR TB outbreaks in the early 1990s were continuing to circulate in NYC. We conclude that the increasing incidence of PZAr, with clear microbial risk factors, underscores the importance of routine PZA drug susceptibility testing andM. tuberculosisgenotyping for the identification, control, and prevention of increasingly resistant organisms.

scholarly journals Multicenter Evaluation of Anyplex Plus MTB/NTM MDR-TB Assay for Rapid Detection of Mycobacterium tuberculosis Complex and Multidrug-Resistant Isolates in Pulmonary and Extrapulmonary Specimens

2015 ◽  
Vol 54 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Michela Sali ◽  
Flavio De Maio ◽  
Francesca Caccuri ◽  
Federica Campilongo ◽  
Maurizio Sanguinetti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Rapid Detection ◽  
Acid Fast Bacillus ◽  
Isoniazid Resistance ◽  
Predictive Values ◽  
Content Type ◽  
Mdr Tb ◽  
Smear Testing ◽  
Acid Fast Bacillus Smear

The rapid diagnosis of tuberculosis (TB) and the detection of drug-resistantMycobacterium tuberculosisstrains are critical for successful public health interventions. Therefore, TB diagnosis requires the availability of diagnostic tools that allow the rapid detection ofM. tuberculosisand drug resistance in clinical samples. Here, we performed a multicenter study to evaluate the performance of the Seegene Anyplex MTB/NTM MDR-TB assay, a new molecular method based on a multiplex real-time PCR system, for detection ofMycobacterium tuberculosiscomplex (MTBC), nontuberculous mycobacteria (NTM), and genetic determinants of drug resistance. In total, the results for 755 samples (534 pulmonary and 221 extrapulmonary samples) were compared with the results of smears and cultures. For pulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 86.4% and 75.0%, respectively, and the specificities were 99% and 99.4%. For extrapulmonary specimens, the sensitivities of the Anyplex assay and acid-fast bacillus smear testing were 83.3% and 50.0%, respectively, and the specificities of both were 100%. The negative and positive predictive values of the Anyplex assay for pulmonary specimens were 97% and 100%, respectively, and those for extrapulmonary specimens were 84.6% and 100%. The sensitivities of the Anyplex assay for detecting isoniazid resistance in MTBC strains from pulmonary and extrapulmonary specimens were 83.3% and 50%, respectively, while the specificities were 100% for both specimen types. These results demonstrate that the Anyplex MTB/NTM MDR-TB assay is an efficient and rapid method for the diagnosis of pulmonary and extrapulmonary TB and the detection of isoniazid resistance.

scholarly journals Performance of a Highly Sensitive Mycobacterium tuberculosis Complex Real-Time PCR Assay for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting: a Prospective Intervention Study

2018 ◽  
Vol 56 (5) ◽  
Author(s):  
Víctor Vinuesa ◽  
Rafael Borrás ◽  
María Luisa Briones ◽  
María Ángeles Clari ◽  
Vicenta Cresencio ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Real Time ◽  
Real Time Pcr ◽  
Acid Fast Bacillus ◽  
Pcr Assay ◽  
Content Type ◽  
Antituberculosis Treatment ◽  
Low Prevalence ◽  
Acid Fast Bacillus Smear ◽  
Respiratory Specimens

ABSTRACT The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacillus smear microscopy, tested by a real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTi me MTB PCR), and cultured in mycobacterial media. Seventeen patients tested positive by PCR (5 were acid-fast bacillus smear positive and 12 acid-fast bacillus smear negative), and Mycobacterium tuberculosis was recovered from cultures for 12 of them. Patients testing positive by PCR and negative by culture ( n = 5) were treated and deemed to have responded to antituberculosis therapy. There were no PCR-negative/culture-positive cases, and none of the patients testing positive for nontuberculous mycobacteria ( n = 20) yielded a positive PCR result. The data indicated that routine testing of respiratory specimens from patients with presumptive tuberculosis by the RealTi me MTB PCR assay improves the tuberculosis diagnostic yield and may reduce the time to antituberculosis treatment initiation. On the basis of our data, we propose a novel mycobacterial laboratory algorithm for tuberculosis diagnosis.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

scholarly journals Mutation ofRv2887, amarR-Like Gene, Confers Mycobacterium tuberculosis Resistance to an Imidazopyridine-Based Agent

2015 ◽  
Vol 59 (11) ◽  
pp. 6873-6881 ◽  
Author(s):  
Kathryn Winglee ◽  
Shichun Lun ◽  
Marco Pieroni ◽  
Alan Kozikowski ◽  
William Bishai
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Efflux Pump ◽  
Transcriptional Regulator ◽  
Cross Resistance ◽  
Loss Of Function ◽  
Strong Activity ◽  
Content Type ◽  
Novel Drug

ABSTRACTDrug resistance is a major problem inMycobacterium tuberculosiscontrol, and it is critical to identify novel drug targets and new antimycobacterial compounds. We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based agent, MP-III-71, with strong activity againstM. tuberculosis. In this study, we evaluated mechanisms of resistance to MP-III-71. We derived three independentM. tuberculosismutants resistant to MP-III-71 and conducted whole-genome sequencing of these mutants. Loss-of-function mutations inRv2887were common to all three MP-III-71-resistant mutants, and we confirmed the role ofRv2887as a gene required for MP-III-71 susceptibility using complementation. The Rv2887 protein was previously unannotated, but domain and homology analyses suggested it to be a transcriptional regulator in the MarR (multiple antibiotic resistance repressor) family, a group of proteins first identified inEscherichia colito negatively regulate efflux pumps and other mechanisms of multidrug resistance. We found that two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action of MP-III-71 and that mutation ofRv2887abrogates their activity. We also used transcriptome sequencing (RNA-seq) to identify genes which are differentially expressed in the presence and absence of a functional Rv2887 protein. We found that genes involved in benzoquinone and menaquinone biosynthesis were repressed by functional Rv2887. Thus, inactivating mutations ofRv2887, encoding a putative MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective antimycobacterial compound that shows no cross-resistance to existing antituberculosis drugs. The mechanism of resistance ofM. tuberculosisRv2887mutants may involve efflux pump upregulation and also drug methylation.

Progressive neurological deficits with benign intracerebral cysts

1986 ◽  
Vol 65 (5) ◽  
pp. 706-709 ◽  
Author(s):  
Yoko Nakasu ◽  
Jyoji Handa ◽  
Kazuyoshi Watanabe
Keyword(s):  
Histological Examination ◽  
Computerized Tomography ◽  
Cyst Wall ◽  
Benign Lesion ◽  
Ct Scanning ◽  
Neurological Deficits ◽  
Review Of The Literature ◽  
Content Type ◽  
Ct Findings ◽  
Fine Print

✓ Two patients with benign intracerebral cysts are reported and a brief review of the literature is given. Although computerized tomography (CT) scanning is useful in detecting a variety of intracerebral cysts, the CT findings are not specific for any lesion. An exploratory operation with establishment of an adequate route of drainage and a histological examination of the cyst wall are mandatory in the management of patients with a progressive but benign lesion.

scholarly journals A Novel 6-Benzyl Ether Benzoxaborole Is Active against Mycobacterium tuberculosisIn Vitro

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Nipul Patel ◽  
Theresa O'Malley ◽  
Yong-Kang Zhang ◽  
Yi Xia ◽  
Bjorn Sunde ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Liquid Medium ◽  
Inhibitory Concentration ◽  
Solid Medium ◽  
Eukaryotic Cells ◽  
Intracellular Bacteria ◽  
Benzyl Ether ◽  
Content Type ◽  
Resistant Mutants

ABSTRACT We identified a novel 6-benzyl ether benzoxaborole with potent activity against Mycobacterium tuberculosis. The compound had an MIC of 2 μM in liquid medium. The compound was also able to prevent growth on solid medium at 0.8 μM and was active against intracellular bacteria (50% inhibitory concentration [IC50] = 3.6 μM) without cytotoxicity against eukaryotic cells (IC50 > 100 μM). We isolated resistant mutants (MIC ≥ 100 μM), which had mutations in Rv1683, Rv3068c, and Rv0047c.

Spinal cord arteriovenous malformation with an associated lymphatic anomaly

1990 ◽  
Vol 73 (5) ◽  
pp. 768-773 ◽  
Author(s):  
Gary E. Kraus ◽  
Richard D. Bucholz ◽  
Thomas R. Weber
Keyword(s):  
Spinal Cord ◽  
Lymphatic System ◽  
Vascular Lesions ◽  
Dietary Manipulation ◽  
Paravertebral Muscle ◽  
Content Type ◽  
Muscle Fascia ◽  
Spinal Osteomyelitis ◽  
The Central Nervous System ◽  
Spinal Cord Arteriovenous Malformation

✓ Spinal cord arteriovenous malformations (AVM's), like other vascular anomalies of the central nervous system, can be associated with similar vascular lesions of the skin and viscera. A 7-year-old girl, who presented with rapidly progressing paraplegia, was found to have a spinal cord AVM, cutaneous angioma, and a chylous malformation of the lymphatic system. She had previously undergone treatment for a posterior thoracic cutaneous angioma. At surgery, upon incision of the paravertebral muscle fascia, viscous pale fluid was encountered emanating from a foramen in the thoracic lamina. The spinal AVM was resected in spite of concern that the abnormality represented spinal osteomyelitis. Postoperatively, there was full return of function in the lower extremities, along with recurrent episodes of chylothorax, which slowly came under control with dietary manipulation. A review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented, and the association of cutaneous and central angiomas is discussed. Finally, the treatment of chylothorax is delineated.

scholarly journals Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Amy Ellis ◽  
Alexis Balgeman ◽  
Mark Rodgers ◽  
Cassaundra Updike ◽  
Jaime Tomko ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mhc Class Ii ◽  
Nonhuman Primates ◽  
Content Type ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Cynomolgus Macaques ◽  
Mhc Haplotype

ABSTRACT Nonhuman primates can be used to study host immune responses to Mycobacterium tuberculosis. Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited major histocompatibility complex (MHC) genetic diversity, such that MHC-identical animals can be infected with M. tuberculosis. Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 CFU of the M. tuberculosis Erdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFU M. tuberculosis. All animals mounted similar T-cell responses to CFP-10 and ESAT-6. Two epitopes in CFP-10 were characterized, and the MHC class II alleles restricting them were determined. A third epitope in CFP-10 was identified but exhibited promiscuous restriction. The CFP-10 and ESAT-6 antigenic regions targeted by T cells in MCMs were comparable to those seen in cases of human M. tuberculosis infection. Our data lay the foundation for generating tetrameric molecules to study epitope-specific CD4 T cells in M. tuberculosis-infected MCMs, which may guide future testing of tuberculosis vaccines in nonhuman primates.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

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