Non-tubercular Mycobacteria Research Articles

An Atypical Etiology for Granulomatous Mediastinal Lymphadenopathy in an Immunocompetent Adult Male

Abstract Nontuberculous mycobacteria (NTM) are widely distributed microorganisms that have the potential to cause severe illness in humans, especially those with compromised immune systems. In adults, the disease mainly manifests as chronic pulmonary disease. Few case reports are available on lymphadenopathy caused by nontubercular mycobacterium in children, primarily affecting the cervical lymph nodes. However, it is exceptionally rare for an immunocompetent adult to develop mediastinal lymphadenopathy due to NTM infection. We present a case of posttubercular fibrocavitary lung disease with mediastinal adenopathy in an immunocompetent male. The initial clinical suspicion was the reactivation of tuberculosis. However, the cultures from the mediastinal node aspirate obtained by Endo Bronchial Ultra Sound guided Trans Bronchial Needle Aspiration (EBUS-TBNA) and the bronchoalveolar lavage showed growth of nontubercular mycobacterium. Our literature search only revealed a case report discussing mediastinal lymphadenopathy associated with NTM in an immunocompetent individual.

Drug Resistance in Osteoarticular Tuberculosis: A Study From an Endemic Zone.

The present study was undertaken to determine the incidence of drug resistance against anti-tubercular drugs among patients from an endemic zone. Methodology: Forty consecutive clinico-radiologically diagnosed patients of osteoarticular tuberculosis (29: spine, 11: extraspinal) were enrolled. Pus from needle aspiration was taken in 31 cases, tissue following spinal decompression in seven, synovial in one, and sinus edge biopsy in one. The pus/tissue was subjected to acid-fast bacilli (AFB) staining and liquid culture, sensitivity to 13 anti-tubercular drugs (Isoniazid (INH), rifampicin (RIF), kanamycin (KAN), amikacin (AMK,) capreomycin (CAP), ethionamide (ETH), levofloxacin (LEV), moxifloxacin (MOX), linezolid (LNZ), para-amino-salicylic acid (PAS), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFO)) were checked, and histopathological/cytopathological examination and molecular tests were performed. Results: The mean age of patients was 29.07(9-65) years; 21 were female and 19 were male. The diagnostic accuracy for tuberculosis was 20% by AFB smear, 65% by liquid culture, 82.5% by histopathology, and 90% by cartridge-based nucleic acid amplification testing (CBNAAT). All culture-positive isolates were identified as Mycobacterium tuberculosis with no non-tubercular Mycobacterium. The drug resistance detected on CBNAAT was 11.1%, line probe assay (LPA) first line was 15.4%, LPA second line was 4%, and liquid drug susceptibility testing (DST) 11.5%. We detected 15.4% INHresistance, 11.1% RIF, 7.6% LEV, 3.8% MOX and PAS. No resistance was detected against second-line injectable drugs (SLID), ETH, LNZ, BDQ, DLM, and CFO. Conclusions: No single laboratory modality can ascertain the diagnosis in all cases; hence, samples should be sent for all tests in tandem. In the presence of insufficient samples, tissue may be subjected to CBNAAT and histopathology to arrive at tissue diagnosis. In this subset, overall drug resistance incidence was 12.5% (5/40) with one patient each of isolated INH and RIF resistance, one of multidrug-resistance (MDR), and two of pre-extensively drug-resistant (pre-XDR). Primary drug resistance came out to be 11.1% (4/36) with one patient each of isolated INH and RIF resistance, one ofMDR, and one Pre-XDR.

Mucoadhesive Rifampicin-Liposomes for the Treatment of Pulmonary Infection by Mycobacterium abscessus: Chitosan or ε-Poly-L-Lysine Decoration.

Mycobacterium abscessus (Mabs) is a dangerous non-tubercular mycobacterium responsible for severe pulmonary infections in immunologically vulnerable patients, due to its wide resistance to many different antibiotics which make its therapeutic management extremely difficult. Drug nanocarriers as liposomes may represent a promising delivery strategy against pulmonary Mabs infection, due to the possibility to be aerosolically administrated and to tune their properties in order to increase nebulization resistance and retainment of encapsulated drug. In fact, liposome surface can be modified by decoration with mucoadhesive polymers to enhance its stability, mucus penetration and prolong its residence time in the lung. The aim of this work is to employ Chitosan or ε-poly-L-lysine decoration for improving the properties of a novel liposomes composed by hydrogenated phosphatidyl-choline from soybean (HSPC) and anionic 1,2-Dipalmitoyl-sn-glycero-3-phosphorylglycerol sodium salt (DPPG) able to entrap Rifampicin. A deep physicochemical characterization of polymer-decorated liposomes shows that both polymers improve mucoadhesion without affecting liposome features and Rifampicin entrapment efficiency. Therapeutic activity on Mabs-infected macrophages demonstrates an effective antibacterial effect of ε-poly-L-lysine liposomes with respect to chitosan-decorated ones. Altogether, these results suggest a possible use of ε-PLL liposomes to improve antibiotic delivery in the lung.

Synthesis of New Derivatives of Leaf-Eating Ant Toxic Gland Pheromone Compounds and Investigation of their Biological Properties

‌Background: The anti-mycobacterial characteristics of 2-pyrazinoic acid esters have been discovered through recent research. Research has demonstrated that the pyrazine ring and the alkyl part of these compounds interact with the enzyme phytynetase, which in turn inhibits the interaction between NADPH and mycobacterial fatty acids synthase, the enzyme responsible for synthesizing the fatty acids required for the cell wall of mycobacteria. Materials and Methods: Targeted pyrazinoic acid molecules have been synthesized, their structure verified by spectroscopic data, and their anti-mycobacterial activity against Mycobacterium TB H37Rv at a dose of 10 micrograms per milliliter assessed in order to test this theory. Significant anti-mycobacterial capabilities were shown by several compounds, including 3c, 3J, and 3M, which inhibited mycobacterial growth by 45.7%, 45.4%, and 51%, respectively. Findings: The results showed that the compounds exhibited little toxicity and did not inhibit macrophage cell proliferation. Pyrazinamide had significant antibacterial and antifungal activity, despite its lack of fatal action against non-tubercular mycobacteria and both Gram-positive and Gram-negative bacteria. Compound 3B, for example, exhibited excellent antibacterial properties against Gram-positive bacteria, such as S. aureus, with a minimum inhibitory concentration (MIC) of 125 micrograms per milliliter. Conversely, the compounds showed equally potent antibacterial properties against Gram-negative bacteria. Interestingly, compared to Gram-positive bacteria, the ester produced from maltol exhibited greater antibacterial efficacy against Gram-negative bacteria. Compounds synthesized with biodegradable groups also exhibited time-dependent toxicity against K562 leukemia cancer cells in MTT measurements, with compounds 3e and 3J displaying IC50 values of 25 micromolars. Conclusion: After synthesizing pyrazinoic acid monoterpene esters, spectral data was used to confirm their structures. When their biological characteristics were assessed, toxicity studies against K562 leukemia cells produced encouraging results. Through the use of Thio Ester-mediated activation of 2-pyrazinoic acid by 2, 2-dibenzothiazole disulfide and triphenylphosphine, 6-aminopenicillanic acid (6-APA) was coupled with pyrazinoic acid.

Evaluation of Immunohistochemistry Technique for Diagnosis of Extrapulmonary Tuberculosis in Biopsy Tissue Specimen as Compared to Composite Diagnostic Criteria.

Diagnosis of extrapulmonary tuberculosis (EPTB) has been challenging owing to its paucibacillary nature and diverse clinical manifestations. Immunohistochemistry (IHC) on biopsy specimens has presented a new perspective toward improving tuberculosis diagnosis. MPT64 is a unique antigen that has shown high sensitivity and specificity compared to other conventional techniques in its ability to diagnose tuberculosis as well as differentiate it from nontubercular mycobacteria. In this study, we aimed to analyze the utility of anti-MPT64 in the diagnosis of EPTB. In this cross-sectional study, conducted over a period of 1 year, 52 nonrepetitive samples from 52 participants with a presumptive diagnosis of EPTB were collected and processed. The specimens were subjected to Ziehl-Neelsen staining, GeneXpert, tissue culture by mycobacterium growth indicator tube, H and E staining, and IHC with anti-MPT64. The sensitivity and specificity of anti-MPT64 was computed against a composite diagnostic criterion. Fifty-two consecutive participants satisfying the study criteria were recruited. The mean age of the study population was 37.35 ± 18.71 years. Lymph node specimen accounted for majority of the specimen processed (n = 20, 38.5%). The sensitivity of anti-MPT64 in the diagnosis of EPTB was 68.29%, specificity was 90.90%, positive predictive value was 96.55%, and negative predictive value was 43.47%, when composite criteria were considered standard for diagnosis. Immunohistochemical staining by anti-MPT64 is useful in establishing microbiological diagnosis of EPTB on biopsy specimens.

Inhibition of the Niemann-Pick C1 protein is a conserved feature of multiple strains of pathogenic mycobacteria

Mycobacterium tuberculosis (Mtb) survives and replicates within host macrophages (MΦ) and subverts multiple antimicrobial defense mechanisms. Previously, we reported that lipids shed by pathogenic mycobacteria inhibit NPC1, the lysosomal membrane protein deficient in the lysosomal storage disorder Niemann-Pick disease type C (NPC). Inhibition of NPC1 leads to a drop in lysosomal calcium levels, blocking phagosome-lysosome fusion leading to mycobacterial survival. We speculated that the production of specific cell wall lipid(s) that inhibit NPC1 could have been a critical step in the evolution of pathogenicity. We therefore investigated whether lipid extracts from clinical Mtb strains from multiple Mtb lineages, Mtb complex (MTBC) members and non-tubercular mycobacteria (NTM) inhibit the NPC pathway. We report that inhibition of the NPC pathway was present in all clinical isolates from Mtb lineages 1, 2, 3 and 4, Mycobacterium bovis and the NTM, Mycobacterium abscessus and Mycobacterium avium. However, lipid extract from Mycobacterium canettii, which is considered to resemble the common ancestor of the MTBC did not inhibit the NPC1 pathway. We conclude that the evolution of NPC1 inhibitory mycobacterial cell wall lipids evolved early and post divergence from Mycobacterium canettii-related mycobacteria and that this activity contributes significantly to the promotion of disease.

Discovery and Optimization of 6-(1-Substituted pyrrole-2-yl)-s-triazine Containing Compounds as Antibacterial Agents.

Antimicrobial drug resistance is a major health issue plaguing healthcare worldwide and leading to hundreds of thousands of deaths globally each year. Tackling this problem requires discovery and development of new antibacterial agents. In this study, we discovered novel 6-(1-substituted pyrrole-2-yl)-s-triazine containing compounds that potently inhibited the growth of Staphylococcus aureus regardless of its methicillin-resistant status, displaying minimum inhibitory concentration (MIC) values as low as 1 μM. The presence of a single imidazole substituent was critical to the antibacterial activity of these compounds. Some of the compounds also inhibited several nontubercular mycobacteria. We have shown that these molecules are potent bacteriostatic agents and that they are nontoxic to mammalian cells at relevant concentrations. Further development of these compounds as novel antimicrobial agents will be aimed at expanding our armamentarium of antibiotics.

Comparative study of different methods of microscopy followed by a culture method in the detection of mycobacterium tuberculosis in clinically and radiologically suspected cases of pulmonary tuberculosis

To compare the sensitivity of 2 microscopic methods for the diagnosis of Mycobacterium tuberculosis (M.tb) along with culture and drug susceptibility testing to first line drugs.: The cross-sectional study comprises 200 suspected cases of pulmonary tuberculosis both clinically and radiologically in KIMS, Bangalore over a period of 2 years. Samples (sputum/BAL fluid) were collected, processed and stained by Ziehl Neelson (ZN) and Fluorescent methods. Culture and drug susceptibilty testing was done for Streptomycin, Isoniazid, Rifampicin and Ethambutol by Mycobacterium growth indicator tube (MGIT) method after decontamination.Fischer’s test : 1. Out of 200 samples: 1.120 were male and 80 were female; 2. 18 were positive by Ziehl Neelson, 21 by Fluorescent and 28 by culture; 3. Majority of the patients belonged to age group 41-50 years (23%); 4. InMGIT, 26 were M.tb and 2 were Non-tubercular mycobacteria; 5. Out of 26 M.tb isolates, 4 were resistant to streptomycin, 6 to isoniazid, 2 to rifampicin and 9 to ethambutol.1. The sensitivity of Fluorescent staining (64.28%) is higher than that of Ziehl-Neelson (51.7%); 2. In MGIT, 26 were M.tb and 2 were Non tubercular mycobacteria; 3. 2 were Multi-drug resistant- tuberculosis (MDR-TB) This study made us aware of the need for prompt detection, identification and appropriate treatment of Tuberculosis due to the rising incidence of MDR-TB.

Multidrug resistant superbugs in pyogenic infections: a study from Western Rajasthan, India.

Introductionthe crude mortality rate due to infectious diseases in India is approximately 417 per one lakh persons and pyogenic infections are one of the significant contributor. Poor antimicrobial stewardship in India has led to an increase in multidrug resistant superbugs in both community as well as hospital settings. The aim of this study was to identify the bacterial etiology of pyogenic infections and to evaluate their antimicrobial resistance profile.Methodsthis is a retrospective observational study from January, 2018 to December, 2018. A total 1851 samples, collected as a part of patient care were included in this study. Specimens were subjected to culture on Blood agar and MacConkey agar and incubated at 37°C for 48 hours. Species identification was done as per standard laboratory protocol. Antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion according to Clinical and Laboratory Standards Institute guidelines.Resultsof total 1851 samples, culture was positive in 61.54%. A total 70.59%, Gram negative organisms were isolated followed by Gram positive cocci in 45.48%, yeast in 1.05%, coryneform bacteria in 0.79% and in one case, non-tubercular mycobacteria was isolated. Staphylococcus aureus (30.9%) was the predominant organism isolated. Most common multi drug resistant isolates were Klebsiella spp. (74.79%) and Acinetobacter spp. (74.32%).Conclusionthis study gives an insight about the prevalence and common etiology of pyogenic infections along with their antimicrobial resistance profile in north western region of India. This study will contribute in formulating antibiotic stewardship program by selecting the antibiograms of pyogenic isolates.

Modeling Tubercular ESX-1 Secretion Using Mycobacterium marinum.

Pathogenic mycobacteria cause chronic and acute diseases ranging from human tuberculosis (TB) to nontubercular infections. Mycobacterium tuberculosis causes both acute and chronic human tuberculosis. Environmentally acquired nontubercular mycobacteria (NTM) cause chronic disease in humans and animals. Not surprisingly, NTM and M. tuberculosis often use shared molecular mechanisms to survive within the host. The ESX-1 system is a specialized secretion system that is essential for virulence and is functionally conserved between M. tuberculosis and Mycobacterium marinumM. marinum is an NTM found in both salt water and freshwater that is often used to study mycobacterial virulence. Since the discovery of the secretion system in 2003, the use of both M. tuberculosis and M. marinum has defined the conserved molecular mechanisms underlying protein secretion and the lytic and regulatory activities of the ESX-1 system. Here, we review the trajectory of the field, including key discoveries regarding the ESX-1 system. We highlight the contributions of M. marinum studies and the conserved and unique aspects of the ESX-1 secretion system.

Study of the prevalence of Multidrug-Resistant Pulmonary Tuberculosis (MDR-TB) in Western Rajasthan using line probe assay.

Objective:To determine the prevalence of MDR-TB and find out the incidence of drug resistance using molecular diagnostic method. Line probe assay (LPA) is based on the principle of multiplex PCR is used to detect MTB (Mycobacterium tuberculosis) complex as well as its sensitivity to rifampicin and isoniazid.Method:This is a hospital-based prospective observational study. The sputum of MDR-TB suspected patients was subjected to Ziehl-Neelsen staining and smear positive samples were analyzed by LPA. Decontamination and digestion of the samples was done using the NALC- NaOH method (as defined in RNTCP guidelines). DNA extraction was done from the decontaminated samples using Geno Lyse kit. After DNA extraction, detection of MTB complex and rifampicin and/or INH resistance was done with the help of line probe assay (LPA) using GenoType ® MTBDRplus version 2.0.Results:Out of the 156 smear-positive sputum samples, 140 samples had LPA valid results. The most common age group of positive TB samples in this study was 30-40 years (26.42%). Twenty-five samples (17.85%) were found to be rifampicin resistant and 22 (15.71%) samples were found resistant to isoniazid. Sixteen patients (11.42%) were detected MDR. Nine patients (6.42%) were monoresistant to rifampicin and six patients (4.28%) were monoresistant to isoniazid. “Sputum positive retreatment cases” had the highest detection rate for MDR TB.Conclusion:Line probe assay is an economical and time saving method for the detection of MDR-TB and serves as a lifesaving tool for early diagnosis and treatment. This calls for a widespread national use of this assay. The detection of around 10% ZN-positive patients, who were not showing MTB complex in LPA may be a hidden iceberg for non-tubercular mycobacteria.

Infectious versus non-infectious causes of oligoarticular inflammatory arthritis: A prospective study from a tertiary care hospital in north India

Oligoarticular arthritis (inflammation of upto 4 joints) has a wide range of infectious and non-infectious etiologies. The aim of our study was to identify the features which could help in the differentiation of infectious from non-infectious arthritis. The study was prospective and observational, and included 100 patients with oligoarticular inflammatory arthritis. The final diagnosis was made using standard diagnostic criteria and the patients were categorized into infectious and non-infectious groups. Among the 100 patients who were recruited, the following final diagnosis were made: peripheral spondyloarthritis (n = 37), axial spondyloarthritis (n = 11), tuberculosis (n = 19), brucellosis (n = 6), septic arthritis (n = 6), gouty arthritis (n = 5), early rheumatoid arthritis (n = 5), non-tubercular mycobacteria (n = 2), SLE (n = 2), post-chikungunya arthritis (n = 2), acute lymphocytic leukaemia (n = 1), pachydermoperiostosis (n = 1), sarcoidosis (n = 1) and juvenile idiopathoic arthritis (n = 1). The patients were categorized into two groups: infectious (33) and non-infectious (60). The presence of monoarthritis, clinically-significant weight loss, hepatomegaly, splenomegaly and erosive arthritis were significantly more common in the infectious group as compared to the non-infectious group.

Evaluation of QuantiFERON-TB Gold test for the diagnosis of tubercular infection in children

BackgroundTuberculin skin test (Mantoux test) is a known intradermal skin prick test for detection of tubercular infection in children and adult population. A new diagnostic test QuantiFERON-TB (QFT) Gold developed in 2005 and approved by the US Food and Drug Administration has good sensitivity and specificity for diagnosis of tubercular infection. MethodsIn this prospective study, 125 children who were being evaluated for tubercular infection or disease were administered Mantoux test and at the same time a blood sample was drawn for the interferon gamma estimation and evaluated by this new diagnostic assay, i.e., QFT Gold assay. ResultsSensitivity and specificity of QFT test calculated was 96.4% and 81% respectively, whereas the negative predictive value and positive predictive value were 91.9% and 90.9% respectively. The sensitivity and specificity of the Mantoux test was found to be 89.2% and 59.5% respectively. The Cohen Kappa coefficient between the Mantoux test and QFT Gold assay for diagnosis of tubercular infection was found to be 0.627 (95% confidence interval: 0.474–0.779; p = 0.0001) in our study, indicating a good agreement between the two tests. ConclusionQFT Gold assay is an effective tool in diagnosing tuberculosis infection in a pediatric population. False positive reactions with tuberculin skin test are common as there is cross-reactivity with non-tubercular mycobacteria (NTM) and BCG vaccination. Both sensitivity and specificity of QFT test were better than those of the tuberculin skin test. Therefore, it is better than the tuberculin skin test, and the diagnostic yield is better. However, this test should not be used as gold standard for diagnosis of tubercular disease in children.

Opportunistic Infections, Is Non Hodgkin Lymphoma One of the Risk Factors for Mortality?

Background:Opportunistic infections (OI's) are defined as infections that are more frequent or more severe because of immunosuppression. Conditions like HIV infections, Hematopoietic stem cell transplantation, autoimmune diseases like SLE and RA have been established as risk factors for increased mortality in OI. Studies suggest that lymphomas are a risk factor for mortality associated with OI's like Tuberculosis and candida (Silva et al, 2005; Chen et al, 2014) probably due to underlying immunodeficiency and therapeutic exposures inducing prolonged lymphopenia. Data describing association of underlying Non-Hodgkin Lymphoma (NHL) on mortality associated with OI's is limited. Our objective was to study impact of NHL on in‐hospital mortality of patients hospitalized with OI's.Methods:We analyzed data from the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample, between 2010 and 2014 using the ICD-9 codes for Opportunistic infections (OI) which included tuberculosis (010-018), non-tubercular mycobacteria (031), cytomegalovirus (078.5), Herpes Zoster( 053), Candidiasis(112.4), Toxoplasmosis (130), Pneumocystis (136.3), Cryptococcosis(117.5), Listerosis (027.0), Nocardiosis (039), Aspergillosis (117.3) coccidiomycosis (114), histoplasmosis (115), blastomycosis (116.0) . The subset of this cohort with NHL excluding lymphoid leukemias listed as a secondary diagnosis were collected for analysis. Baseline characteristics including age, race, gender, Charlson comorbidity index, and infection with HIV etc. were analyzed for patients with admitted with OI's, with and without underlying diagnosis of NHL. Our primary outcome was in-hospital mortality. Characteristics associated with in‐hospital mortality were identified using multivariable logistic regression.ResultsBetween 2010 and 2014, a total of 1,81,016 admissions were identified with a primary diagnosis of OI. A total of 4442 admissions had an underlying diagnosis of NHL. Mean age of patients hospitalized with OI's with NHL, was higher (65.4 ±0.52 years vs 58.9±0.14years, p<0.05 ), and 54.7% of the patients were males. Racial distribution of the patients with NHL was similar to those suggested in previous studies (Li et sl, 2016), with 73.19% patients being whites. Patient's median income, hospital bed-size and teaching status of hospital all were found to be significant risk factors (p<0.05) for mortality. When adjusted for the above mentioned factors, as well as HIV or Transplant status of patients, NHL was found to be an independent factor for mortality with an odds ratio of 1.34 (p=0.03).ConclusionOI's constitute a major cause of morbidity and mortality in immunocompromised patients. There is limited data from a nationwide analysis which evaluates association of opportunistic infections and lymphoma as an independent marker of mortality. Our study suggests that NHL is an independent risk factor for mortality in patients who were admitted in the hospital for OI's. Further studies should be considered to the role of primary prophylaxis for conditions like PCP to avoid morbidity and mortality associated with these conditions. This will help reduce health care cost burden associated with such hospitalizations. DisclosuresNo relevant conflicts of interest to declare.

Mycobacterium tuberculosis and non-tubercular mycobacterium infection in women with unexplained infertility from eastern India

Genital tuberculosis (GTB) is an important cause of female infertility, especially in developing countries. The positive results of polymerase chain reaction (PCR) in endometrial GTB in the absence of tubal damage raise the possibility of the detection of sub-clinical or latent disease, with doubtful benefits of treatment. This study aims to evaluate the Mycobacterium tuberculosis (MTB) and Non-tubercular Mycobacterium (NTM) infection by using Real-PCR technique in the menstrual blood samples of 120 unexplained infertile women. In this cross-sectional study, 120 infertile women with unexplained infertility aged 20-35 yr old and normal hysterosalpingography findings were taken. Menstrual blood in the first 12 hr of menstruation containing the endometrial tissues from each participant was tested for MTB and NTM by Real-Time PCR. Among the selected 120 patients, only two were found to be positive for MTB infection. All remaining participants were negative for MTB infection. All participants were negative for NTM infection at the endometrium. Although, studies have indicated that PCR is a useful method in diagnosing early GTB disease in infertile women with no demonstrable evidence of tubal or endometrial involvement, our study showed that GTB is not the major problem in women with unexplained infertility.

Extrapulmonary infections associated with nontubercular mycobacteria in immunocompetent patients: A study of two cases

Nontuberculous mycobacteria (NTM) or atypical mycobacteria are abundantly found in the environment. Extrapulmonary infections are most commonly caused by Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium, and Mycobacterium kansasii. Risk factors for infection include both accidental/surgical trauma, all procedures involving implants, retained biomaterial. The isolation rate of NTM from India has been reported ranging from 0.5% to 8.6%. We report two culture-proven cases of infection caused by NTM. The present cases emphasize the importance of considering NTM in the differential diagnosis of nonhealing ulcers whether corneal or skin and soft tissue infections. The following core competencies are addressed in this article: Medical knowledge, Patient care.

An extremely rare association of Sweet's syndrome with active pulmonary tuberculosis

Sweet's syndrome is a skin manifestation of various systemic infections, drugs, malignancies and autoimmune disorders. There are very few case reports describing the relationship between Sweet's syndrome and non-tubercular mycobacterium infection. Further development of Sweet's syndrome secondary to mycobacterium tuberculosis (active pulmonary tuberculosis) is extremely uncommon and this is the second well established case reported from India. Here we report a forty eight year old man who presented with multiple erythematous and tender plaques over neck, palms and sides of soles. He also had high grade fever, headache, myalgias, cough, chest pain and difficulty in breathing. With clinical possibilities of (1) Sweet's syndrome with pulmonary involvement and (2) Sweet's syndrome secondary to pulmonary infection, we send the skin biopsy for histopathological examination and also advised routine laboratory plus imaging investigations to find out the underlying cause. Clinical and lab parameters together with the biopsy report fulfilled the diagnostic criteria for Sweet's syndrome. Further chest X-ray findings, demonstration of acid fast bacilli of mycobacterium tuberculosis on sputum smear microscopy and MGIT report confirmed the diagnosis of pulmonary tuberculosis. Patient was put on colchicine and standard anti-tubercular drugs. Significant improvement was noticed in skin lesions within five days of treatment and no recurrence has been seen for the past six months.

Line probe assay for detection of Mycobacterium tuberculosis complex: An experience from Central India.

Background & objectives:Mycobacterium tuberculosis complex may sometimes not be detected in sputum samples of suspected multidrug-resistant tuberculosis (MDR-TB) patients by line probe assay (LPA) even though they are smear positive for acid-fast bacilli (AFB). This retrospective analysis was attempted to understand and document our experience with LPA for detection of M. tuberculosis complex and diagnosis of MDR-TB under programmatic conditions.Methods:One thousand two hundred and ninety four sputum samples of MDR-TB suspects that were smear positive for AFB, and received from February to November 2013, were tested by LPA for the presence of M. tuberculosis complex and resistance to isoniazid (INH) and rifampicin as per the diagnostic mandate of an accredited reference laboratory. As per the mandate, those samples that were negative for M. tuberculosis complex were cultured, and the growth again tested by LPA. A retrospective analysis of the results was carried out.Results:M. tuberculosis complex could be detected in 1217 (94.04%) but not in 77 (5.9%) of smear-positive sputum samples. Of the 1217 positive samples, 232 (19.1%) were MDR, 130 (10.6%) were rifampicin monoresistant and 101 (8.3%) were INH monoresistant. Seven hundred and fifty four (61.9%) strains were found to be pansensitive. Overall, 5.1 per cent of the sputum samples were negative for M. tuberculosis complex by LPA and culture. In at least 10 (0.77%) sputum samples smear positive for AFB, M. tuberculosis complex could not be identified by LPA though M. tuberculosis was present, as evidenced by culture positivity.Interpretation & conclusions:LPA is a robust technique for diagnosis of drug-resistant TB that has provided the basis for rapid and effective control of drug-resistant TB in India. While the reasons for concomitantly negative LPA and culture results of smear-positive sputum samples from MDR-TB suspects may be many, the possible presence of non-tubercular mycobacteria in these samples and the likelihood of inappropriate therapy in these patients cannot be ruled out. Addition of culture to the diagnostic algorithm may enhance the diagnostic yield.

Rapid Screening of MDR-TB in Cases of Extra Pulmonary Tuberculosis Using Geno Type MTBDRplus.

BackgroundDrug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes.MethodsA total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method.ResultsOf 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours.ConclusionThe problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and due attention on patients should be given. Routine use of Geno Type MTBDRplus assay for the diagnosis of MDR-EPTB can substantially reduce the time between diagnosis and drug therapy. Culture along with Geno Type MTBDRplus assay could be a solution for rapid and accurate diagnosis of MDR-TB in low bacillary non sputum specimens.

Multiple lumps in the breast due to Mycobacterium fortuitum

Although breast tissue is the most resistant to tuberculosis, its incidence is increasing worldwide. High incidence of breast tuberculosis is presumed in India. The rapidly growing nontubercular mycobacteria, such as Mycobacterium fortuitum and Mycobacterium chelonae, are of increasing clinical importance because infections due to these organisms are often hospital acquired. The true incidence of M. fortuitum is unknown but it has been estimated to be between 4 and 6 cases per one million people. It causes skin or soft tissue infections following trauma or surgery. Breast infection with M. fortuitum is very uncommon. The most common clinical presentation of breast tuberculosis is a painless lump. Multiple lumps are rarely reported. The culture and molecular studies are the keystone for differentiation of various mycobacterium species. We report one such case of a 25-year-old female presenting with multiple painless lumps due to M. fortuitum infection in the left breast.