Clinico-radiological and bronchoscopic predictors of microbiological yield in sputum negative tuberculosis in Pakistan

To determine association of clinico-radiological factors and radiological activity with diagnostic yield in sputum-smear negative tuberculosis (TB). Prospective observational study in Military Hospital Rawalpindi from July to December 2018. Adult patients having no contraindications to bronchoscopy were included. HIV positive patients and those on anti-tuberculosis therapy for more than one week were excluded. High-Resolution Computed tomography (HRCT) findings were classified based on active and inactive tuberculosis features. Washings were sent for Acid-Fast Bacillus (AFB) smear, GeneXpert assay and cultures. Out of 215 patients, 42.3% (91) were diagnosed with microbiological or histological evidence of TB. On univariate analysis, cavitation (p-value <0.001), soft-tissue nodules (p-value 0.04), and endobronchial mucosal changes (p-value 0.02) were associated with culture positivity. Presence of cavitation (OR= 4.10; CI= 2.18,7.73; p-value<0.001) was the only independent predictor of microbiological yield. Diagnostic yield was 70%, 50%, 12.5% and 8.6% in patients with definitely active, probably active, indeterminate and inactive tuberculosis HRCT features respectively. Sensitivity, specificity, positive predictive value and negative predictive value of HRCT active TB were 95.38% (95% CI 87.10 -99.04), 48.00 % (95% CI 39.78 -56.30), 44.29% (95% CI 40.31 -48.33), 96.00 % (95%CI 88.70 -98.66) respectively. There was no significant association between age groups, smoking status and gender with diagnosis of tuberculosis in our study. Radiological activity and certain visualized bronchoscopic changes were associated with good diagnostic performance and can be used as predictive factors in diagnosis of active smear negative tuberculosis.

Efficacy of GeneXpert in Diagnosing Smear Negative Pulmonary Tuberculosis and Comparison to Culture

Objectives: Aim of present study is to observe the efficiency of GeneXpert MTB/RIF Assay in comparison to MTB culture on Lowenstein Jensen media in diagnosis of smear negative pulmonary tuberculosis cases. Methods: This descriptive study was carried out in The University of Lahore in collaboration with King Edward Medical University/Mayo Hospital Lahore 11th September, 2020 to 10th April 2021. Smear negative for acid fast bacilli patients enrolled for anti TB treatment were the target population. After taking informed consent, patients were asked to submit first morning sputum sample for culture on Lowenstein Jensen Medium and GeneXpert. Results: A total of 345 smear negative TB patients were diagnosed clinically and/or on the basis of radiological findings with mean age of 38.28±17.93,consisting of 47.5% male and 52.5% females recruited in this study. History of TB contact was present among 41.4% patients whereas history of smoking and diabetes remained to be 27.2% and 17.4% respectively. Culture showed significantly higher rate (35.1%) (p-value <0.05) of detection of MTB as compared to GeneXpert (21.5%). A sensitivity of 56.01% was calculated for GeneXpert whereas for culture on LJ medium it was 60.63%. Conclusion: Sensitivity of GeneXpert MTB/RIF Assay is a bit low in diagnosing the SNPT patients as compared to the culture but still registers itself as a handsome tool in terms of promptness and definite detection of MTB complex. Further provision of rifampicin susceptibility is bonus in same time.

Xpert MTB/RIF use is associated with earlier treatment initiation and culture conversion among patients with sputum smear-negative multidrug-resistant tuberculosis

Background While rapid molecular diagnostic tests for tuberculosis (TB) have decreased detection time of M. tuberculosis and drug resistance, whether their use improves clinical care and outcomes is uncertain. To address these knowledge gaps, we evaluated whether use of the Xpert MTB/RIF assay impacts treatment and clinical outcome metrics among patients treated for sputum smear-negative multidrug-resistant (MDR)-TB. Methods A retrospective cohort of adult patients initiating treatment for sputum smear-negative MDR-TB at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia from 2011-2016. The Xpert MTB/RIF was introduced in Georgia in 2010 and implemented into programmatic use in 2014. Exposure was availability of an Xpert result at time of diagnosis. Time to second-line treatment initiation, sputum culture conversion, and end-of-treatment outcomes were determined from. Time to event was compared using a Cox proportional hazards model. Results Among 151 patients treated for sputum smear-negative MDR-TB (96% culture positive), the Xpert was utilized in the clinical management of 78 (52%) patients and not used in 73 (48%). An adjusted analysis controlling for potential confounders found that patients in the Xpert group had shorter median time to second-line treatment (13 vs. 56 days, adjusted hazard ratio [aHR]10.21, p&lt;0.0001) and culture conversion (61 vs. 93 days, aHR 1.93, p&lt;0.001). There was no difference in treatment outcomes. Conclusions Use of the Xpert in the management of sputum smear-negative MDR-TB decreases time to second-line therapy and sputum culture conversion, providing evidence of its clinical impact and supporting its programmatic utility.

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study

Background Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. Methods To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). Results 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. Conclusion These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial

OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001).CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

Diagnostic Value of Bronchoalveolar Lavage Examination in Sputum Negative Patients for AFB in Suspected Pulmonary Tuberculosis

Background: Pulmonary tuberculosis (PTB) is one of the most common infections worldwide, more commonly among the developing countries like Bangladesh. So its early detection and prompt treatment was a challenge and the burden of diagnostic challenge was higher if the patients smear negative for Acid Fast Bacilli (AFB). Objective: Evaluate the diagnostic value of Bronchoalveolar lavage (BAL) for diagnosis of suspected Pulmonary Tuberculosis (PTB) whose sputum for AFB smear neagtive. Materials and Methods: A cross-sectional observational reserach was undertaken where 50 patients were included on the basis of specific inclusion and exclusion criteria. All patients who had negative smear for AFB but highly suspected for PTB underwent fibreoptic bronchoscopy to collect Bronchoalveolar lavage (BAL) fluid for diagnostic testing in the form of BAL for AFB and mycobacterial culture in Lowenstein Jensen medium. Results: The Male predominacy 29 (58%) was obserevd among the smear negative PTB patients. Clinically more than seventy percent (72%) presents with fever then cough with sputum and haemoptysis 62% and 32% respectively. Radiological cavitation 33 (66%) was the most common x-ray findings. After analysis of BAL for AFB about 31 (62%) patient found positive and on culture about mycobacterial growth found in 29 (58%) patients. Conclusion: Bronchoalveolar lavage had a superior diagnostic value in patients with smear negative suspected pulmonary tuberculosis. KYAMC Journal.2021;12(02): 84-87