scholarly journals Turnaround Time for Microbiological Testing of Tuberculosis in Routine Clinical Practice and Time to Patient Initiation on Treatment, Iganga Hospital, Uganda: 2012-2017

2021 ◽  
Author(s):  
Angella Musewa ◽  
Lilian Bulage ◽  
Joseph Frank Maganda ◽  
Alex Riolexus Ario
Keyword(s):  
Clinical Practice ◽  
Treatment Initiation ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Routine Clinical Practice ◽  
Smear Microscopy ◽  
Reference Laboratory ◽  
Time To Initiation ◽  
Mdr Tb ◽  
Microbiological Testing

Abstract Background: Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (Mtb) that is resistant to atleast isoniazid and rifampicin. Delayed diagnosis and treatment initiation lead to increased transmission and poor clinical outcomes. Although GeneXpert MTB/RIF detects Mtb and rifampicin resistance within 2 hours, the TB control program needs to understand the turnaround time (TAT) from specimen collection to treatment initiation and its impact on treatment outcomes for patients with Rif-resistant TB in Uganda. We quantified the TAT overall and at each step of the process for diagnosis of Rif-resistant TB in routine clinical practice and time to initiation on appropriate treatment over a 5-year period.Methods: We conducted a retrospective study in Iganga General Hospital, Eastern Uganda. Both Rif-resistant and MDR TB cases are recorded in the same register. We abstracted data from the MDR-TB clinic and laboratory registers (Form 2A and 096B) at Iganga Hospital, 2012-2017, including dates for smear microscopy, Xpert MTB/RIF, initiating MDR-TB patients on treatment after the Xpert MTB/RIF test, and dates for Drug Susceptibility Testing (DST). We performed descriptive and survival analysis to estimate the TAT for microbiological testing and time to initiation on treatment among MDR-TB patients.Results: Overall, we analyzed sixty-three (63) records, including specimens from Iganga Hospital patients and referrals from other health facilities. Of 63 records, 81% (51/63) had microscopy results, 97% (61/63) had Xpert MTB/RIF results, and 98% (62/63) had DST results. The median TAT for smear microscopy was the same day or within 1 day for 38/51 (75%) of the patients, ranging from 2-31 days for the rest. TAT for Xpert MTB/RIF results was the same day or within 1 day for 45/61 (75%), while the rest ranged from 2-183 days. Treatment initiation was within 28 days for 30/61 (50%). Reporting results for DST, took a median time of 13 days (IQR: 10-40 days) with an overall range of 0-334 days. Conclusion: Prompt Xpert MTB/RIF testing and result reporting allows timely treatment initiation. We recommend timely release of DST results by the National Tuberculosis Reference Laboratory or decentralization of DST services so as to mitigate delays and improve patient re-evaluation.

scholarly journals Discordance of the Repeat GeneXpert MTB/RIF test for Rifampicin Resistance Detection among Patients Initiating MDR-TB Treatment in Uganda

2020 ◽  
Author(s):  
Willy Ssengooba ◽  
Jean Iragena ◽  
Kevin Komakech ◽  
Iginitius Okello ◽  
Joanitah Nalunjogi ◽  
...  
Keyword(s):  
Treatment Initiation ◽  
Sputum Sample ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Smear Microscopy ◽  
First Line ◽  
Tb Treatment ◽  
Mulago National Referral Hospital ◽  
Mdr Tb ◽  
National Referral Hospital

Abstract We recruited all patients with Xpert Rifampicin-Resistant (RR)-TB detected, referred to the MDR-TB ward at Mulago National Referral Hospital, Kampala, Uganda for MDR-TB treatment initiation between September 2017 and October 2019. Using baseline samples collected for patients screened for STREAM 2 trial, smear microscopy, repeat Xpert test and first-line MTBDRplus assay were done. Culture-based drug-susceptibility testing was done on discordant samples. We analysed for factors associated with discordant results and false RR as determined as no RR detected by at least two of the methods used (reference standard). Of 126/130 patients who had results of repeat Xpert, 97 (77.0%) had M. tuberculosis detected of which 81 (83.5%) had RR-detected, 1 (1.0%) indeterminate. A total of 10/96 (10.4%) patients were rifampicin susceptible by at least two of the methods. Having false Xpert RR was associated with low bacillary load measured by high cycle threshold (Ct) value i.e. low (Ct 22–28) and very low (Ct > 28) of the initial Xpert test 0.09 (0.05; 0.01–1.08) and 0.02 (0.01; 0.01–0.35) respectively. Our results show that a repeat Xpert test on another sputum sample for patients with initial low M. tuberculosis detected RR-detected, would exclude 10% of the TB patients from unnecessary MDR-TB treatment initiation.

scholarly journals PHARMACOKINETIC STUDY OF BEDAQUILINE AMONG INDIAN MDR-TB PATIENTS IN CLINICAL SETTINGS

2021 ◽  
Author(s):  
Vamshikrishna Gone ◽  
Shalini Thakur ◽  
Nithya Valupadasu ◽  
Yashaswini Akoju ◽  
Bhuvana Chandra Pasupuleti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Routine Clinical Practice ◽  
Multi Drug Resistance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Clinical Settings ◽  
Diseased Person ◽  
Mdr Tb ◽  
Us Fda

Bedaquiline, a novel drug was approved for the treatment of multi-drug resistance tuberculosis (MDR-TB) by the US FDA in 2012. It is majorly caused because of the transmission of multi-resistant strain from a diseased person to a healthy individual and by genetic factors. Safety, efficacy, and bactericidal activity of Bedaquiline were reported in various studies, but the pharmacokinetic analysis of Bedaquiline in clinical settings was unclear. This study serves as evidence for the physicians regarding the pharmacokinetic data and managing drug therapy and for better patient outcome in routine clinical practice. This study is conducted in a total of 58 patients with newly diagnosed, smear-positive, MDR-TB patients who received Bedaquiline as per RNTCP guidelines. Plasma samples were collected after the Bedaquiline administration. The patient samples were analyzed. The pharmacokinetic data were drawn by using software kinetic-2000, version 5.03.The observed Cmax was 2523.08 ng/mL, Tmax was reached at 4 hrs, AUC(0-24) was 21727.1 ng *hr/mL, AUMC (0-24) was 222953.8 ng *hr2/mL. Whereas the half-life of the drug was found at 7 .02 hrs and mean residence time (MRT) was found to be 10.25 hrs respectively. The data was even on the 14th day of therapy. The Cmax is shown to be 5937.1ng/mL reaching the Cmax at about 5 hours. While the AUC(0-24) was found to be 65780 ng *hr/mL. Conclusively, pharmacokinetic parameters were evaluated and found to be within the desired limits with minimal changes. This method can be further used for the quantification of Bedaquiline in routine clinical practice.

scholarly journals Discordance of the Repeat GeneXpert MTB/RIF test for Rifampicin resistance detection among patients Initiating MDR-TB treatment in Uganda

2021 ◽  
Author(s):  
Willy Ssengooba ◽  
Jean de Dieu Iragena ◽  
Kevin Komakech ◽  
Iginitius Okello ◽  
Joanitah Nalunjogi ◽  
...  
Keyword(s):  
Drug Susceptibility ◽  
Cross Sectional Study ◽  
Drug Susceptibility Testing ◽  
Resistance Rate ◽  
Rifampicin Resistance ◽  
P Value ◽  
Smear Microscopy ◽  
Cross Sectional ◽  
Tb Treatment ◽  
Mdr Tb

Abstract Background The Global Laboratory Initiative (GLI) guidelines recommend to repeat GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low-pretest probability of rifampicin-resistance (RR). Design/Methods In a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/MDR-TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra and MTBDRplus assays were done on sputum specimens. Culture-based drug-susceptibility testing (DST) were done on discordant specimens. We analysed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA or culture DST (reference comparator). Results A total of 126/130 patients had repeat XpertMTB/RIF results of which, 97 (77.0%) had M. tuberculosis detected of whom, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%) whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%). Low bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results, aOR (p-value: 95%CI), 0.04 (0.01; 0.00-0.37) and 0.02 (0.01; 0.01-0.35) respectively. Conclusion Our findings show a high false-positive rifampicin resistance rate in low TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti MDR-TB therapy.

scholarly journals The fourth national anti-tuberculosis drug resistance survey in Peru

2020 ◽  
Vol 24 (2) ◽  
pp. 207-213
Author(s):  
N. Quispe ◽  
L. Asencios ◽  
C. Obregon ◽  
G. E. Velásquez ◽  
C. D. Mitnick ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Contact Tracing ◽  
Sputum Smear ◽  
Reference Laboratory ◽  
First Line ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Previously Treated

BACKGROUND: Peru has one of the highest burdens of multidrug-resistant tuberculosis (MDR-TB), but universal drug susceptibility testing (DST) has not yet been achieved.OBJECTIVE: To estimate the proportion of drug resistance among smear-positive TB patients in Peru.DESIGN: From September 2014 to March 2015, we performed a national drug resistance survey of patients aged ≥15 years; TB was diagnosed based on sputum smear positivity. We performed DST at the National Reference Laboratory of the Peruvian National Institute of Health, Lima, Peru, using the proportion method in Middlebrook 7H10 agar for four first-line drugs and six second-line drugs, and the Wayne method for pyrazinamide.RESULTS: Of the 1908 new and 272 previously treated patients included in the analysis, 638 (29.3%) patients had resistance to at least one first-line drug. MDR-TB was diagnosed in 7.3% of new and 16.2% of previously treated patients (P < 0.001). There were five (0.2%) patients with extensively drug-resistant TB.CONCLUSION: MDR-TB has increased to 7.3% in new patients from 5.3% in the previous survey, indicating that resistance to anti-tuberculosis drugs is increasing in Peru. Ongoing community transmission of resistant strains highlights an urgent need for early diagnosis, optimised treatment and effective contact tracing of MDR-TB patients.

scholarly journals Diagnostic Accuracy and Turnaround Time of the Xpert MTB/RIF Assay in Routine Clinical Practice

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77456 ◽  
Author(s):  
Nakwon Kwak ◽  
Sun Mi Choi ◽  
Jinwoo Lee ◽  
Young Sik Park ◽  
Chang-Hoon Lee ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Diagnostic Accuracy ◽  
Turnaround Time ◽  
Routine Clinical Practice

scholarly journals Is deployement of diagnostic test alone enough? Comprehensive package of interventions to strengthen TB laboratory network: three years of experience in Burkina Faso

2021 ◽  
Author(s):  
Riccardo Alagna ◽  
Adjima Combary ◽  
Elisa Tagliani ◽  
Léon Tinnoga Sawadogo ◽  
Tandaogo Saouadogo ◽  
...  
Keyword(s):  
Burkina Faso ◽  
Technical Assistance ◽  
Critical Role ◽  
Laboratory Data ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Smear Microscopy ◽  
Laboratory System ◽  
Mdr Tb ◽  
One Year

Abstract BackgroundsThe laboratory plays a critical role in tuberculosis (TB) control by providing testing for diagnosis, treatment monitoring, and surveillance at each level of the health care system. Weak accessibility to TB diagnosric services still represents a big concern in many limited resources’ countries. Here we report the experience of Burkina Faso in implementing a comprehensive intervention packages to strengthen TB laboratory capacity and diagnostic accessibility.MethodsThe intervention lasted from October 2016 to December 2018 and focused on two main areas: i) development of strategic documents and policies; ii) implementation of TB diagnostic technology. National TB laboratory data were collected between 2016 and 2018 and evaluated according to five programmatic TB laboratory indicators: i) Percentage of notified new and relapse TB cases with bacteriological confirmation; ii) Percentage of notified new and relapse TB cases tested by Xpert MTB/RIF; iii) Percentage of notified, bacteriologically confirmed TB cases with a drug susceptibility testing (DST) result for rifampin; iv) Percentage of notified MDR-TB cases on the estimated number of MDR-TB cases; v) The ration between the number of smear microscopy and Xpert MTB/RIF tests. We compared these indicators between a one year (2016-2017) and two years (2016-2018) timeframe.ResultsFrom 2016 to 2018, the percentage of bacteriologically confirmed cases increased from 67% to 71%. The percentage of new and relapse TB cases notified tested by Xpert MTB/RIF increased from 18% in 2016 to 46% in 2018 and the percentage of bacteriologically confirmed cases with an available DST result for rifampicin increased from 27% in 2016 to 66% in 2018.. The percentage of notified MDR-TB cases on the estimated number of MDR-TB cases in 2018 increased from 43% in 2016 to 78% in 2018. In 2018, the ratio between the number of smear microscopy and Xpert MTB/RIF tests decreased from 53% in 2016 to 21% in 2018. ConclusionWe demonstrated that the implementation of a comprehensive package of laboratory strengthening interventions led to a significant improvement of all indicators. External technical assistance played a key role in speeding up the TB laboratory system improvement process.

Clinical interpretation of drug susceptibility tests in tuberculosis

2020 ◽  
Vol 16 ◽  
Author(s):  
Rafael Laniado-Laborín
Keyword(s):  
Drug Resistance ◽  
Drug Regimen ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Therapeutic Decisions ◽  
Mdr Tb ◽  
Frequent Mutations ◽  
Susceptibility Tests

: Prompt and accurate diagnosis of drug resistance is essential for optimal treatment of drug-resistant tuberculosis. However, only 20% of the more than half a million patients eligible for the treatment of MDR-TB/RR-TB receive an appropriate drug regimen. Drug-resistant TB regimens must include a sufficient number of effective medications, a significant challenge for clinicians worldwide, as most are forced to make therapeutic decisions without any, or very little information on drug susceptibility testing. Although phenotypic DST is still commonly regarded as the gold standard for determining M. tuberculosis susceptibility to antituberculosis drugs, it has several limitations, mainly its prolonged turnaround time. Molecular methods based on M. tuberculosis genomic DNA sequencing have been developed during the past two decades, to identify the most common mutations involved in drug resistance. The Xpert®MTB/RIF is a real-time polymerase chain reaction that offers results in less than two hours and has an overall sensitivity for rifampin resistance of 96% and 98% specificity. Line probe assays (LPAs) are commercial DNA strip-based tests for detecting the most frequent mutations responsible for resistance to rifampin, isoniazid, fluoroquinolones, and second-line injectable drugs. Discrepancies between phenotypic and genotyping methods are a problem that the clinician will face in everyday practice. However, any resistance result (with any type of test) in a person with risk factors for harboring resistant microorganisms should be considered initially resistant while the results of complementary tests are available.

scholarly journals Epidemiological profile of patients with rifampicin-resistant tuberculosis: an analysis of the Uganda National Tuberculosis Reference Laboratory Surveillance Data, 2014–2018

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gloria Bahizi ◽  
Robert Kaos Majwala ◽  
Stevens Kisaka ◽  
Abdunoor Nyombi ◽  
Kenneth Musisi ◽  
...  
Keyword(s):  
Laboratory Data ◽  
Drug Susceptibility Testing ◽  
Surveillance Data ◽  
Reference Laboratory ◽  
Tb Control ◽  
Resistant Tuberculosis ◽  
National Tuberculosis ◽  
Mdr Tb ◽  
Laboratory Surveillance ◽  
Previously Treated

Abstract Background Drug-resistant tuberculosis (DR-TB), including rifampicin-resistant tuberculosis (RR-TB) and multidrug-resistant tuberculosis (MDR-TB, or RR-TB with additional isoniazid resistance), presents challenges to TB control. In Uganda, the GeneXpert test provides point-of-care testing for TB and rifampicin resistance. Patients identified with RR-TB receive culture-based drug susceptibility testing (DST) to identify additional resistance, if any. There are few data on the epidemiological profiles of current DR-TB patients in Uganda. We described patients with RR-TB in Uganda and assessed the trends of RR-TB to inform TB control interventions. Methods We identified patients with RR-TB whose samples were referred for culture and DST during 2014–2018 from routinely-generated laboratory surveillance data at the Uganda National Tuberculosis Reference Laboratory. Data on patient demographics and drug sensitivity profile of Mycobacterium tuberculosis isolates were abstracted. Population data were obtained from the Uganda Bureau of Statistics to calculate incidence. Descriptive epidemiology was performed, and logistic regression used to assess trends. Results We identified 1474 patients whose mean age was 36 ± 17 years. Overall incidence was 3.8/100,000 population. Males were more affected by RR-TB than females (4.9 vs. 2.7/100,000, p ≤ 0.01). Geographically, Northern Uganda was the most affected region (IR = 6.9/100,000) followed by the Central region (IR = 5.01/100,000). The overall population incidence of RR-TB increased by 20% over the evaluation period (OR = 1.2; 95% CI 1.15–1.23); RR-TB in new TB cases increased by 35% (OR = 1.35; 95% CI 1.3–1.4) and by 7% in previously-treated cases (OR = 1.07; 95% CI 1.0–1.1). Of the 1474 patients with RR-TB, 923 (63%) were culture-positive of whom 670 (72%) had full DST available. Based on the DST results, 522/670 (78%) had MDR-TB. Conclusion Between 2014 and 2018, the incidence of RR-TB increased especially among newly-diagnosed TB patients. We recommend intensified efforts and screening for early diagnosis especially among previously treated patients. Mechanisms should be in put to ensure that all patients with RR-TB obtain DST.

scholarly journals Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 208 ◽  
Author(s):  
Tuelo Mogashoa ◽  
Pinkie Melamu ◽  
Brigitta Derendinger ◽  
Serej D. Ley ◽  
Elizabeth M. Streicher ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility Testing ◽  
World Health ◽  
Fluoroquinolone Resistance ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Second Line ◽  
Mdr Tb ◽  
Line Drug

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (M.tb) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates. A total of 66 M.tb isolates received at the National Tuberculosis Reference Laboratory between March 2012 and October 2013 with resistance to isoniazid, rifampicin or both were analyzed in this study. The genotypes of the M.tb isolates were determined by spoligotyping and second-line drug susceptibility testing was done using the Hain Genotype MTBDRsl line probe assay version 2.0. The treatment outcomes were defined according to the Botswana national and World Health Organization (WHO) guidelines. Of the 57 isolates analyzed, 33 (58%) were MDR-TB, 4 (7%) were additionally resistant to flouroquinolones and 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs. The most common fluoroquinolone resistance-conferring mutation detected was gyrA A90V. All XDR-TB cases remained smear or culture positive throughout the treatment. Our study findings indicate the importance of monitoring drug resistant TB cases to ensure rapid detection of second-line drug resistance.

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