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

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.

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Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0314 ◽

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.

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

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1134 ◽

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.

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Treatment outcome among cases of multidrug-resistant tuberculosis (MDR TB) in Western India: A prospective study

Journal of Infection and Public Health ◽

10.1016/j.jiph.2015.11.011 ◽

2016 ◽

Vol 9 (4) ◽

pp. 478-484 ◽

Cited By ~ 8

Author(s):

Sangita V. Patel ◽

Kapil B. Nimavat ◽

Patel B. Alpesh ◽

Lipy K. Shukla ◽

Kalpita S. Shringarpure ◽

...

Keyword(s):

Treatment Outcome ◽

Prospective Study ◽

Multidrug Resistant ◽

Western India ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

A Prospective Study

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03008-15 ◽

2016 ◽

Vol 60 (8) ◽

pp. 4786-4792 ◽

Cited By ~ 14

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.

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Patient- and provider-related factors in the success of multidrug-resistant tuberculosis treatment in Colombia

Revista Panamericana de Salud Pública ◽

10.26633/rpsp.2021.74 ◽

2021 ◽

Vol 45 ◽

pp. 1

Author(s):

Gloria Mercedes Puerto Castro ◽

Fernando Nicolás Montes Zuluaga ◽

Jacqueline Elizabeth Alcalde-Rabanal ◽

Freddy Pérez

Keyword(s):

Treatment Outcome ◽

Treatment Success ◽

Multidrug Resistant ◽

Insurance Scheme ◽

Related Factors ◽

Successful Treatment Outcome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Nursing Professionals

Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusion. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians’ and nurses’ knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

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Socio-demographic determinants of treatment outcome in multidrug resistant tuberculosis cases registered under Programmatic management of drug resistant tuberculosis services in Amritsar, Punjab

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20192345 ◽

2019 ◽

Vol 6 (6) ◽

pp. 2688

Author(s):

Manisha Nagpal ◽

Sarthak Chawla ◽

Priyanka Devgun ◽

Naresh Chawla

Keyword(s):

Treatment Outcome ◽

Treatment Success ◽

Public Health Problem ◽

Educational Status ◽

Multidrug Resistant ◽

Major Public Health Problem ◽

Cross Sectional ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Background: Multidrug resistant tuberculosis (MDR-TB) has become a major public health problem. It is associated with significant morbidity and mortality. The treatment success rate worldwide is around 50%.Methods: This cross-sectional study was conducted on all MDR-TB patients who were registered and being treated under PMDT services in Amritsar district from 1st April 2014 to 31st March 2015. The treatment outcome with their socio-demographic determinants was ascertained. Data management and analysis was done by using Microsoft excel and SPSS.Results: Out of 87 MDR-TB patients, 57 (65.5%) were males and 30 (34.4%) were females. The various treatment outcomes observed were- 30 (34.5%) cured, 19 (21.8%) treatment completed, 18 (20.7%) died, 13 (14.9%) defaulted, 4 (4.6%) shifted to XDR TB regime and 3 (3.4%) failure.Conclusions: On statistical analysis, it was observed that age (p=0.000), marital status (p=0.024), educational status (p=0.011) and occupation (p=0.002) were significantly associated with the treatment outcome. Other factors like sex, type of family and socio-economic status did not affect the treatment outcome.

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

BMJ Open ◽

10.1136/bmjopen-2020-040862 ◽

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.

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KAMI-PMO TB (EDUKASI DAN PENDAMPINGAN PENGAWAS MENELAN OBAT TB) DALAM PENGENDALIAN MDR TB

Jurnal Bakti Masyarakat Indonesia ◽

10.24912/jbmi.v3i2.9475 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Mareta Dea Rosaline ◽

Santi Herlina

Keyword(s):

Multidrug Resistant ◽

T Test ◽

P Value ◽

Test Analysis ◽

Pulmonary Tb ◽

Drug Ingestion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Paired T Test

Tuberculosis control in Indonesia is still not optimal. The problem of MDR TB (Multidrug-Resistant Tuberculosis) is an obstacle to controlling TB in Indonesia. MDR TB is caused by no response from TB germs to treatment isoniazid and rifampicin, anti-tuberculosis drugs. TB incidence rate in Serang district ranks second in Banten Province after Tangerang. The number of pulmonary TB cases is due to the lack of public knowledge and awareness about pulmonary TB disease. To reduce the adverse effects of MDR TB requires the involvement of cadres or family members who controlling drug ingestion (PMO). The form of activities carried out through the formation of cadres to care for TB through the KAMI-PMO TB (Education and Assistance for TB Medication Supervisors) in Desa Baros, Kabupaten Serang. The purpose is to increase the commitment, ability, and knowledge of cadres as coordinator of PMO (Drug Swallow Supervisor) to control MDR TB. The method of implementing activities is counseling, demonstrations, and assistance to cadres. The media used were PPT, WE-PMO TB Booklet, and educational videos. The result of the training was an increase in the ability of cadres in providing PMO counseling by 87%. The Paired T-Test analysis results showed a p-value of 0.000, which means that the training conducted affected cadres' knowledge of PMO TB. In conclusion, education and assistance to cadres have a good influence in increasing knowledge and abilities. The expected result is TB care cadres can provide aid and become the coordinator of TB PMO (Drug Ingestion Supervisor). ABSTRAK:Pengendalian Tuberculosi di Indonesia masih belum optimal.Permasalahan MDR TB (Multidrug Resistant Tuberculosis) merupakan hambatan pengendalian TB di Indonesia. MDR TB disebabkan tidak ada respon kuman TB terhadap pengobatan isoniazid dan rifampizin yang merupakan obat anti tuberculosis. Angka kejadian TB di kabupaten Serang menempati urutan kedua di Provinsi Banten setelah Tangerang, dan banyaknya kasus TB Paru dikarenakan pengetahuan dan kesadaran masyarakat tentang penyakit TB Paru masih kurang. Untuk mengurangi dampak buruk MDR TB dibutuhkan keterlibatan peran serta kader peduli TB atau anggota keluarga yang berperan dalam pengawasan menelan obat (PMO). Bentuk kegiatan yang dilakukan sebagai bentuk pemberdayaan masyarakat melalui pembentukan kader peduli TB melalui KAMI-PMO TB (Edukasi dan Pendampinga Pengawas Menelan Obat TB) di Desa Baros Kabupaten Serang. Tujuan dari pengabdian masyarakat adalah meningkatkan komitmen, kemampuan dan pengetahuan kader sebagai koordinator PMO (Pengawas Menelan Obat) dalam upaya pengendalian MDR TB. Metode pelaksanaan kegiatan adalah penyuluhan, demontrasi, dan pendampingan kader. Media yang digunakan yaitu PPT, Booklet KAMI-PMO TB , dan video edukasi. Hasil dari kegiatan adalah meningkatnya kemampuan kader dalam memberikan penyuluhan PMO cukup tinggi sebesar 87%. Hasil analisis uji Paired T- Test didapatkan nilai p value 0,000 yang artinya ada pengaruh pelatihan yang dilakukan terhadap pengetahuan kader tentang PMO TB. Kesimpulannya edukasi dan pendampingan kepada kader memiliki pengaruh yang baik dalam meningkatkan pengetahuan dan kemampuan, sehingga hasil yang diharapkan kader peduli TB dapat melakukan pendampingan pada pasien TB dan menjadi koordinator PMO (Pengawas Menelan Obat) TB dalam upaya pengendalian MDR TB

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Genotypic Resistance of Pyrazinamide but Not Minimum Inhibitory Concentration Is Associated With Longer Time to Sputum Culture Conversion in Patients With Multidrug-resistant Tuberculosis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1509 ◽

2020 ◽

Author(s):

Johanna Kuhlin ◽

Lina Davies Forsman ◽

Mikael Mansjö ◽

Michaela Jonsson Nordvall ◽

Maria Wijkander ◽

...

Keyword(s):

Treatment Outcome ◽

Minimum Inhibitory Concentration ◽

Inhibitory Concentration ◽

Multidrug Resistant ◽

Sputum Culture ◽

Sputum Culture Conversion ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Culture Conversion

Abstract Background Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Methods Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992–2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Results Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73–1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. Conclusions In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.

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