scholarly journals Effectiveness of Shorter Treatment Regimen in Multidrug-Resistant Tuberculosis Patients in Pakistan: A Multicenter Retrospective Record Review

2021 ◽  
Author(s):  
Abudl Wahid ◽  
Nafees Ahmad ◽  
Abdul Ghafoor ◽  
Abdullah Latif ◽  
Fahad Saleem ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Retrospective Record Review ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Record Review

In Pakistan, the treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter treatment regimen (STR), that is, 4–6 months of amikacin, moxifloxacin (Mfx), ethionamide, clofazimine (Cfz), pyrazinamide (Z), ethambutol (E), and high-dose isoniazid, followed by 5 months of Mfx, Cfz, Z, and E, was initiated in 2018. However, there is a lack of information about its effectiveness in Pakistani healthcare settings. Therefore, this retrospective record review of MDR-TB patients treated with STR at eight treatment sites in Pakistan aimed to fill this gap. Data were analyzed using SPSS 23. Multivariate binary logistic regression (MVBLR) analysis was conducted to find factors associated with death and treatment failure, and lost to follow-up (LTFU). A P-value < 0.05 was considered statistically significant. Of 912 MDR-TB patients enrolled at the study sites, only 313 (34.3%) eligible patients were treated with STR and included in the current study. Of them, a total of 250 (79.9%) were cured, 12 (3.8%) completed treated, 31 (9.9%) died, 16 (5.1%) were LTFU, and four (1.3%) were declared as treatment failures. The overall treatment success rate was 83.7%. In MVBLR analysis, patients’ age of 41–60 (odds ratio [OR] = 4.9, P-value = 0.020) and > 60 years (OR = 3.6, P-value = 0.035), being underweight (OR = 2.7, P-value = 0.042), and previous TB treatment (OR = 0.4, P-value = 0.042) had statistically significant association with death and treatment failure, whereas patients’ age of > 60 years (OR = 5.4, P-value = 0.040) and previous TB treatment (OR = 0.2, P-value = 0.008) had statistically significant association with LTFU. The treatment success rate of STR was encouraging. However, to further improve the treatment outcomes, special attention should be paid to the patients with identified risk factors.

scholarly journals National treatment outcome and predictors of death and treatment failure in multidrug-resistant tuberculosis in Ethiopia: a 10-year retrospective cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e040862
Author(s):  
Habteyes Tola ◽  
K Holakouie-Naieni ◽  
Mohammad Ali Mansournia ◽  
Mehdi Yaseri ◽  
Dinka Fikadu Gamtesa ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Treatment Failure ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
The Past ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ObjectivesTreatment success rate in patients treated for multidrug-resistant tuberculosis (MDR-TB) is low, but predictors of treatment failure and death have been under-reported. Thus, we aimed to determine the national proportion of treatment success rate in the past 10 years and factors that predict treatment failure and death in patients with MDR-TB in Ethiopia.SettingA retrospective cohort study with a 10-years follow-up period was conducted in 42 MDR-TB treatment-initiating centres in Ethiopia.ParticipantsA total of 3395 adult patients with MDR-TB who had final treatment outcome and who were treated under national TB programme were included. Data were collected from clinical charts, registration books and laboratory reports. Competing risk survival analysis model with robust standard errors (SE) was used to determine the predictors of treatment failure and death.Primary and secondary outcomesTreatment outcome was a primary outcome whereas predictors of treatment failure and death were a secondary outcome.ResultsThe proportion of treatment success was 75.7%, death rate was 12.8%, treatment failure was 1.7% and lost to follow-up was 9.7%. The significant predictors of death were older age (adjusted hazard ratio (AHR)=1.03; 95% CI 1.03 to 1.05; p<0.001), HIV infection (AHR=2.0; 95% CI 1.6 to 2.4; p<0.001) and presence of any grade of anaemia (AHR=1.7; 95% CI 1.4 to 2.0; p<0.001). Unlike the predictors of death, all variables included into multivariable model were not significantly associated with treatment failure.ConclusionIn the past 10 years, although MDR-TB treatment success in Ethiopia has been consistently favourable, the proportion of patients who died is still considerable. Death could be attributed to advanced age, HIV infection and anaemia. Prospective cohort studies are necessary to further explore the potentially modifiable predictors of treatment failure.

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim
Keyword(s):  
Success Rate ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Treatment Success Rate ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

scholarly journals Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China

2016 ◽  
Vol 60 (8) ◽  
pp. 4786-4792 ◽  
Author(s):  
Xubin Zheng ◽  
Rongrong Zheng ◽  
Yi Hu ◽  
Jim Werngren ◽  
Lina Davies Forsman ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Classification And Regression Tree ◽  
Second Line ◽  
Cart Analysis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTOur study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined forM. tuberculosisisolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.

scholarly journals Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

2020 ◽  
pp. 00537-2020
Author(s):  
Philipp du Cros ◽  
Khamraev Atadjan ◽  
Tigay Zinaida ◽  
Tleubergen Abdrasuliev ◽  
Jane Greig ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Fluoroquinolone Resistance ◽  
Second Line ◽  
Serious Adverse Events ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

BackgroundIn 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility.

scholarly journals Effectiveness and Safety of Shorter-Term Regimen (STR) for Multidrug-Resistant Tuberculosis (MDR-TB) Treatment: A Systematic Review of Cohort Studies

2021 ◽  
Author(s):  
Putu Nandika Tungga Yudanti Mahardani ◽  
Dyah Kanya Wati ◽  
Azriel Siloam ◽  
Ni Putu Ayu Savitri ◽  
Arya Krisna Manggala
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Cohort Studies ◽  
Success Rate ◽  
Multidrug Resistant ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Gastrointestinal Problems ◽  
Mdr Tb

The multidrug-resistant tuberculosis (MDR-TB) remains a significant public health burden in term of the successful TB treatment because of the lack awareness of TB drugs administration. Patients infected with MDR-TB are resistant to isoniazid (INH) and rifampicin (RMP) due to genotypic mutation, thus could not adequately treated by the first-line regimen standards. The management of MDR-TB using Short-Term Regimen (STR) is a crucial topic to be discussed due to low success rate of conventional therapy and its long duration. This systematic review aims to further examine the effectiveness and safety of STR to manage MDR-TB. In this systematic review, various cohort studies were searched using standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). The keywords were arranged based on Problem, Intervention, Comparison, and Outcome (PICO). Key terms consisted of multidrug-resistant tuberculosis and short regimen therapy. Seven cohort studies were selected from 314 studies. STR has better therapeutic efficacy and shorter duration than the 2011 WHO regimen for MDR-TB with therapy success rates for each study above 50%. The most effective regimen according to studies in this review is kanamycin-high dose isoniazid-clofazimine-ethambutol-prothionamide- pyrazinamidegatifloxacin (KM-INH-CFZ-EMB-PTH-PZA-GFX) in the intensive phase for 4 months and clofazimine-ethambutol-pyrazinamide-gatifloxacin-prothionamide (CFZ-EMBPZA-GFX-PTH) in the continuation phase for 8 months. The four most reported side effects were gastrointestinal problems, ototoxicity, dysglycemia, and liver problems. In conclusion, STR provides good effectiveness in MDR-TB treatment, in terms of treatment success rate and short therapy duration. Therapy with STR is relatively safe, with minimal side effects that can be tolerated in the majority of individuals.

scholarly journals An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

2020 ◽  
Author(s):  
Wenwen Sun ◽  
Qin Tang ◽  
Jie Wang ◽  
Jinhui Yang ◽  
Fangyou Yu ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Success Rate ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
P Value ◽  
Prospective Clinical Study ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
A Prospective Study

Abstract Background: MDR-TB（multidrug-resistant tuberculosis） remains the challenge with low success rate of treatment. Pasiniazid had been applied in China for two decades, but relevant clinical studies are rare. To verify the efficacy and safety of a regimen containing pasiniazid on MDR-TB, a prospective clinical study was conducted in China. Methods: Patients with MDR-TB satisfied with inclusion criteria were prospectively enrolled into the study from 2017 June to 2018 Dec, given the regimen and followed up, observed the treatment outcome and adverse effect of drugs made up the regimen.Results: A total of 114 patients diagnosed as MDR Pulmonary tuberculosis(MDR-PTB) were enrolled into the study and given the regimen with six months of Capremycin(Cm), Levofloxacin(Lfx), Cycloserine(Cs), Protionamide(Pto), Pyrazinamide(Z) and Pasiniazid（Pa）, followed by 12 months of LfxCsPtoZPa. The overall treatment success rate in all enrolled patients was 79.8% (91/114) while it was significantly higher in newly treated MDR-PTB (91.7%, 33/36) than that in retreated MDR-PTB(74.4%，58/78, p value was 0.03); Patients infected with strains resistant to fluoroquinolones impacted the treatment outcome (P<0.05) while other drugs did not (P >0.05). Pasiniazid was taken safely without adverse reaction during the course of treatment.Conclusions: The long term of anti-MDR-PTB regimen containing Pasiniazid was proved to be effective, safe and inexpensive although it contained injectable agents. This regimen is suited to be applied in areas with poor resource and high TB burden.

scholarly journals Molecular Evaluation of Fluoroquinolone Resistance in Serial Mycobacterium tuberculosis Isolates from Individuals Diagnosed with Multidrug-Resistant Tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01663-20
Author(s):  
Melisa Willby ◽  
Paige Chopra ◽  
Darrin Lemmer ◽  
Katherine Klein ◽  
Tracy L. Dalton ◽  
...  
Keyword(s):  
Treatment Success ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Personal Genome ◽  
Genotypic Resistance ◽  
Phenotypic Resistance ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTFluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Differing levels of resistance are associated with specific mutations within the quinolone-resistance-determining region (QRDR) of gyrA. We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PETTS) with baseline FQ resistance (FQR) or acquired FQ resistance (FQACQR) using an Ion Torrent Personal Genome Machine (PGM) to a depth of 10,000× and reported single nucleotide polymorphisms in ≥1% of reads. FQR isolates harbored 15 distinct alleles with 1.3 (maximum = 6) on average per isolate. Eighteen alleles were identified in FQACQR isolates with an average of 1.6 (maximum = 9) per isolate. Isolates from 78% of FQACQR individuals had mutant alleles identified within 6 months of treatment initiation. Asp94Gly was the predominant allele in the initial FQ-resistant isolates followed by Ala90Val. Seventy-seven percent (36/47) of FQACQR group patients had isolates with FQ resistance alleles prior to changes to the FQ component of their treatment. Unlike the individuals treated initially with other FQs, none of the 21 individuals treated initially with levofloxacin developed genotypic or phenotypic FQ resistance, although country of residence was likely a contributing factor since 69% of these individuals were from a single country. Initial detection of phenotypic resistance and genotypic resistance occurred simultaneously for most; however, phenotypic resistance occurred earlier in isolates harboring mixtures of alleles of very low abundance (<1% of reads), whereas genotypic resistance often occurred earlier for alleles associated with low-level resistance. Understanding factors influencing acquisition and evolution of FQ resistance could reveal strategies for improved treatment success.

scholarly journals Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

2016 ◽  
Vol 48 (4) ◽  
pp. 1160-1170 ◽  
Author(s):  
Carole D. Mitnick ◽  
Richard A. White ◽  
Chunling Lu ◽  
Carly A. Rodriguez ◽  
Jaime Bayona ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Failure Detection ◽  
Multidrug Resistant ◽  
Survival Models ◽  
Smear Microscopy ◽  
Monitoring Method ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

scholarly journals Predicting the Outcomes of New Short-Course Regimens for Multidrug-Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modeling

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Tan N. Doan ◽  
Pengxing Cao ◽  
Theophilus I. Emeto ◽  
James M. McCaw ◽  
Emma S. McBryde
Keyword(s):  
Treatment Duration ◽  
Treatment Success ◽  
Empirical Evaluation ◽  
Multidrug Resistant ◽  
Pharmacodynamic Modeling ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb

ABSTRACT Short-course regimens for multidrug-resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug bedaquiline (BDQ) may have the potential to shorten MDR-TB treatment to less than 6 months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modeling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modeling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (4 months) while still maintaining a very high treatment success rate (100% for daily BDQ for 2 weeks, or 95% for daily BDQ for 1 week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes, then we anticipate clear cost savings and a subsequent improvement in the efficiency of national TB programs.

scholarly journals Clinical Profile and Treatment Evaluation of Rifampicin-Resistant and Multidrug-Resistant Tuberculosis Patients at Dr. Kanujoso Djatiwibowo Public Hospital, Balikpapan

2018 ◽  
Vol 38 (3) ◽  
pp. 135-142
Author(s):  
Randy Adiwinata ◽  
Josephine Rasidi ◽  
Maurits Marpaung
Keyword(s):  
Success Rate ◽  
Public Hospital ◽  
Multidrug Resistant ◽  
Clinical Profile ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Lost To Follow Up

Background: Rifampicin-resistant (RR-TB) and multidrug-resistant tuberculosis (MDR-TB) remains a major health problem worldwide and in Indonesia also become a challenge in total eradication of tuberculosis. Dr. Kanujoso Djatiwibowo Public Hospital (RSKD) Balikpapan is one of the two referral hospitals in East Kalimantan for evaluation and initiation of MDR-TB treatment. The objective of this study is to evaluate clinical profile and treatment of RR-TB and MDR-TB patients at RSKD. Methods: A retrospective cross-sectional study was conducted using data from eTB manager database and medical record of RR-TB and MDR-TB at RSKD from January 2013 to October 2016. Results: Twenty eight RR-TB and MDR-TB patients, most of them were female (53.6%), belong to 35-44 age group (28.6%), housewife (25%), graduated from senior high school (42,9%), malnutrition (28.6%), and relapse cases (50%). Diabetes mellitus and anemia were found in 42,9% and 44.4% of the patients, respectively. The most resistant pattern is rifampicin-resistant TB (57,1%) followed by rifampicin and isoniazid resistant. The most common side effect of TB treatment was gastrointestinal complaints (44.4%). The success rate of MDRTB treatment at RSKD was 20%, followed by 20% mortality, 50% of lost to follow up, 10% of treatment failure, and there are 8 patients still ongoing therapy. Conclusion: Most of the RR-TB and MDR-TB cases were relapse cases. Counseling, education, and support for the patients undergoing MDR-TB treatment are strongly needed to increase success rate and decreasing number of lost to follow up.

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