High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

Naz, Farah; Ahmad, Nafees; Wahid, Abdul; Ahmad, Izaz; Khan, Abdullah; Abubakar, Muhammad; Khan, Shabir Ahmed; Khan, Amjad; Latif, Abdullah; Ghafoor, Abdul

doi:10.1186/s12879-021-06935-6

Cited by 13 publications

(11 citation statements)

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“…For patients with no resistance to any SLD and no documented history of SLD use for ≥ 1 month, LTR comprised of at least 8 months treatment with amikacin (Am)/kanamycin (Km)/ capreomycin (Cm) + levofloxacin (Lfx) + ethionamide (Eto) + cycloserine (Cs) + pyrazinamide (Z) and 12 months treatment with Lfx + Eto + Cs + Z. If a patient had resistance to any SLD or had documented history of SLD use for ≥ 1 month, it was suggested to add para-amino salicylic acid (PAS) to the abovementioned regimen (WHO, 2011;Naz et al, 2021). However, LTR had the drawbacks of poor treatment success rate, 56% globally and 45%-76.9% in various individual cohorts around the world (Ahuja et al, 2012;Carroll et al, 2012;Jain et al, 2014;Sagwa et al, 2014;Ahmad et al, 2015;Hoa et al, 2015;Aibana et al, 2017;Alene et al, 2017;El Hamdouni et al, 2019;Khan et al, 2019;Leveri et al, 2019;Atif et al, 2020;Lan et al, 2020;Phu et al, 2020), acquisition of additional drug resistance during treatment, prolonged treatment duration (≥20 months), being expensive and high incidence of clinically significant adverse events (Ahuja et al, 2012;Carroll et al, 2012;Jain et al, 2014;Sagwa et al, 2014;Ahmad et al, 2015;Hoa et al, 2015;Aibana et al, 2017;Alene et al, 2017;El Hamdouni et al, 2019;Khan et al, 2019;Leveri et al, 2019;Atif et al, 2020;Phu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

et al. 2022

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Objective: To compare the effectiveness of second line injectables containing shorter (duration 9–12 months) and longer treatment regimens (LTR, duration ≥ 20 months) among multidrug-resistant tuberculosis (MDR-TB) patients with no documented resistance and history of treatment with any second-line anti-TB drug (SLD) for ≥ 1 month.Methods: This was an observational cohort study of MDR-TB patients treated at eight PMDT units in Pakistan. Patients’ data from baseline until treatment outcomes were collected from Electronic Nominal Recording and Reporting System. The treatment outcomes of “cured” and “treatment completed” were grouped together as successful, whereas “death,” “treatment failure,” and “lost to follow-up” were collectively grouped as unsuccessful outcomes. Time to sputum culture conversion (SCC) was analyzed using the Kaplan–Meier method and the differences between groups were compared through the log-rank test. Multivariate Cox proportional hazards and binary logistic regression analyses were used to find predictors of time to SCC and unsuccessful treatment outcomes. A p-value < 0.05 was considered statistically significant.Results: A total 701 eligible MDR-TB patients [313 treated with shorter treatment regimen (STR) and 388 treated with LTR at eight centres in Pakistan were evaluated]. Time to achieve SCC was significantly shorter in STR group [mean: 2.03 months, 95% confidence interval (CI):1.79–2.26] than in LTR group (mean: 2.69 months, 95% CI: 2.35–3.03) (p-value<0.001, Log-rank test). Treatment success was higher in STR (83.7%) than in LTR (73.2%) group (p-value <0.001) due to high cure (79.9% vs. 70.9%, p-value = 0.006) and low death (9.9% vs. 18.3%, p-value = 0.002) rates with STR. Treatment with STR emerged the only predictor of early SCC [adjusted Hazards ratio (aHR) = 0.815, p-value = 0.014], whereas, patient’s age of 41–60 (OR = 2.62, p-value<0.001) and >60 years (OR = 5.84, p-value<0.001), baseline body weight of 31–60 (OR = 0.36, p-value = 0.001) and >60 kg (OR = 0.23, p-value <0.001), and treatment with LTR (OR = 1.88, p-value = 0.001) had statistically significant association with unsuccessful treatment outcomes.Conclusion: STR exhibited superior anti-microbial activity against MDR-TB. When compared LTR, treatment with STR resulted in significantly early SCC, high cure, and lower death rates among MDR-TB patients who had no documented resistance and history of treatment with any SLD ≥ 1 month.

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Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

et al. 2022

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“…The causes of DR-TB include poor adherence to treatment, the use of low-quality medicine in the private sector, diagnostic delays, unsupervised therapy, and inadequate follow-up [5]. According to reports, DR-TB was discovered in 3-4% of new pulmonary cases and 18-21% of previously treated patients [6]. Furthermore, there is scarce data on extra-pulmonary drug-resistant tuberculosis in the literature.…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Multidrug-Resistant Tuberculosis Affecting the Pleura

Jamal¹,

Imran²,

Khan³

et al. 2022

Cureus

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The majority of cases with tuberculous pleuritis have negative acid-fast bacilli (AFB) on smear microscopy, making the diagnosis difficult. This case report is based on the successful diagnosis and management of an extra-pulmonary (EP) multidrug-resistant tuberculosis (MDR-TB) patient with a history of lymphoma. Initial tests revealed a right-sided pleural effusion and thickening of the pleura. The closed pleural biopsy, pleural fluid histopathology, culture, and drug sensitivity testing (DST) report revealed Mycobacterium tuberculosis with isoniazid and rifampicin resistance. Based on the DST report, the patient was labeled as a case of MDR-TB and successfully managed with an individualized drug-resistant TB (DR-TB) regimen. With initial negative microscopy and GeneXpert MTB/RIF (Sunnyvale, CA: Cepheid Inc.) reports, this case demonstrated that DR-TB could exist even in the absence of risk factors. Furthermore, it also unveils the importance of line probe assays (LPAs) and culture in identifying MDR-TB. Lymphocytic/exudative pleural effusions and pleural biopsy specimens should be subjected early on to investigations like Xpert/MTB RIF, cultures, and genotypic DST to timely diagnose and treat DR-TB.

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“…At these laboratories, DST against anti-TB drugs was carried out using Agar proportion method on enriched Middlebrook 7H10 medium (BBL; Beckton Dickinson, Sparks, MD, United States) at the following concentrations: RIF (1 µg/ml), INH (0.2 µg/ml), streptomycin (2 µg/ml), ethambutol (EMB) (5 µg/ml), AM (4 µg/ml), KM (5 µg/ml), CM (4 µg/ml), ethionamide (ETO) (5 µg/ml), ofloxacin (OFX) (2 µg/ml) and LFX (1 µg/ml). Whereas, DST for pyrazinamide (PZA) at a concentration of 100 µg/ml was done by using BACTEC Mycobacterial Growth Indicator Tube (MGIT, BD, Sparks, MD, USA) [ 10 , 13 , 22 – 24 ]. Upon availability of DST results, patients diagnosed with XDR-TB were shifted to individualized treatment regimens (ITRs).…”

Section: Methodsmentioning

confidence: 99%

“…ENRS is a combined excel sheet of the following four main TB recoding and reporting registers (i) basic management unit TB register, (ii) second-line TB treatment register (iii) laboratory register for smear microscopy and Xpert MTB/Rif and (iv) laboratory register for culture, Xpert MTB/RIF and DST. ENRS contains information about the patients’ sociodemographic characteristics like age, gender, marital status, residence and smoking, history of TB treatment, treatment centre, duration, regimen and outcome of previous episode of TB treatment, presence of any concurrent medical condition, history of any SLD used, results of Xpert MTB/Rif and LPA, phenotypic DST results, monthly weight, sputum smear microscopy and culture results, treatment regimen for DR-TB and treatment outcomes [ 10 , 13 , 25 ]. We retrieved the abovementioned data from ENRS through a purpose developed data collection form.…”

Section: Methodsmentioning

confidence: 99%

“…A new bacteriological response term bacteriological conversion defined as “a situation in a patient with bacteriologically confirmed TB where at least two consecutive cultures for DR-TB and drug susceptible-TB or smears for drug susceptible-TB, taken on different occasions at least 7 days apart, are negative” has been recently introduced for assessing the effectiveness of anti-TB treatment [ 12 ]. However, as in routine management of DR-TB, sputum smear and culture are done on monthly basis [ 13 ], therefore, sputum culture conversion (SCC) defined as “two successive negative culture specimen obtained at the space of at least one month following a baseline positive culture” [ 14 , 15 ] plays a cardinal role in observing the treatment response, predicting the effectiveness of the regimen, identifying the constraints and deciding about the treatment duration and treatment outcomes of DR-TB patients [ 14 , 16 – 18 ]. In addition to clinical settings, SCC remains the most commonly used surrogate marker for evaluating the efficacy of anti-TB drugs in clinical trials [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study

et al. 2022

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Background There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. Methods This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan–Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. Results A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47–3.53), than those who did not (median: 10 months, 95% CI: 5.24–14.76) (p-value < 0.001, Log-rank test). Patient’s age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7–50.2), 69.9% (95%CI: 61.7–77.2) and 84.9% (95%CI: 78.1–90.3), specificities were respectively, 82.8% (95%CI: 76.9–87.6), 74.6% (95%CI: 68.2–80.4) and 69.4% (95%CI: 62.6–75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7–70.8), 72.7% (95%CI: 67.7–77.2) and 75.8% (95%CI: 71.0–80.1). Conclusion In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

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High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

Cited by 13 publications

References 30 publications

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country

A Rare Case of Multidrug-Resistant Tuberculosis Affecting the Pleura

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study

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