scholarly journals Multidrug-Resistant Tuberculosis during Pregnancy: Two Case Reports and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Minakshi Rohilla ◽  
Bharti Joshi ◽  
Vanita Jain ◽  
Jasvinder Kalra ◽  
G. R. V. Prasad

Multidrug-resistant tuberculosis (MDR-TB) is identified from the time of introduction of antituberculosis treatment and is a known worldwide public health crisis affecting women of reproductive age group. Management issues raised by pregnant women with MDR tuberculosis are challenging due to the limited clinical experience available with the use of second line drugs. We hereby report two cases of MDR-TB during pregnancy: one patient was on second line drugs, while another one was evaluated and diagnosed to have MDR-TB in last trimester. At 6 months of follow-up both mothers and babies are doing well. The approach to such cases along with review of the literature is discussed.

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.


2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Agibothu Kupparam Hemanth Kumar ◽  
Alok Kumar ◽  
Thiruvengadam Kannan ◽  
Rakesh Bhatia ◽  
Dipti Agarwal ◽  
...  

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Solomon Weldegebreal Asgedom ◽  
Mebrahtu Teweldemedhin ◽  
Hailay Gebreyesus

Background. Multidrug-resistant tuberculosis (MDR-TB) has continued to be a challenge for tuberculosis (TB) control globally. Ethiopia is one of the countries with high MDR-TB burden. Objective. The main purpose of this study was to determine the prevalence of MDR-TB and associated factors in Ethiopia. Methods. A systematic review of the literatures on prevalence of MDR-TB and associated factors was conducted in the country. Results. In our electronic search, 546 citations were depicted. Among the total 546 citations described, a total of 22 articles met eligibility criteria and were included in the review article. According to our review, the prevalence of MDR-TB ranged from 0 to 46.3%. The average mean rate of MDR-TB in Ethiopia was found to be 12.6±15.9%. The overall prevalence of MDR-TB in all TB cases was estimated to be 1.4%. From a total of 3849 patients studied, 527 had MDR-TB. Previous exposure to antituberculosis treatment was the most commonly identified risk factor of MDR-TB in Ethiopia. Conclusion. Despite relative decline in incidence of MDR-TB, the distribution and prevalence of MDR-TB continued to be a serious challenge for TB control in Ethiopia. Previous exposure to antituberculosis treatment was also the most common risk factor for MDR-TB. Therefore, strong TB and MDR-TB treatment along with tight introduction of follow-up strategies should be applied for better TB control.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Maria Musso ◽  
Silvia Mosti ◽  
Gina Gualano ◽  
Paola Mencarini ◽  
Rocco Urso ◽  
...  

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
C. Padmapriyadarsini ◽  
Mrinalini Das ◽  
Sharath Burugina Nagaraja ◽  
Mahalakshmi Rajendran ◽  
Richard Kirubakaran ◽  
...  

Background. Preventive therapy for child contacts of multidrug-resistant tuberculosis (MDR-TB) patients is poorly studied, and no consensus about the role and the rationale of chemoprophylaxis has been reached. Objective. To conduct systematic review with an aim to determine the effectiveness of TB preventive therapy in reducing the incidence of TB disease in pediatric contacts of MDR-TB patients. Methods. We conducted a literature search for randomized control trials, cohort studies, and case reports of chemoprophylaxis for pediatric contacts of MDR-TB patients in PubMed, EMBASE, Cochrane Databases of Systematic Reviews, metaRegister of Controlled Trials, and other clinical registries through March 2017, using appropriate search strategy. In addition we searched abstracts from international conferences and references of published articles and reviews. Results. Of the 153 references assessed from various databases, seven studies were identified as relevant after adaption of eligibility criteria and assessed for systematic review. Of these, only two studies contributed data for the pooled meta-analysis. Conclusions. Though the available evidences suggest that the chemoprophylaxis for child contacts of MDR-TB patients is beneficial, data to support or reject preventive therapy is very limited. Further clinical research, in Tb endemic settings like India, needs to be performed to prove the beneficial effect of chemoprophylaxis for pediatric contacts of MDR-TB.


2021 ◽  
Author(s):  
Stellah George George Mpagama ◽  
Happiness C Mvungi ◽  
Peter M Mbelele ◽  
Hadija H Semvua ◽  
Alphonce A Liyoyo ◽  
...  

Abstract Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality . N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm , an interventional arm of NAC 900mg daily , and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania . The minimum anticipated sample size is 66 ; with 22 participants in each arm. ADR monitoring will be performed at baseline and daily follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, and electrocardiogram. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis . Adverse drug events will be analysed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model. Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress , it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations. Trial registration: PACTR202007736854169 Registered 03 July 2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12163


2016 ◽  
Vol 60 (8) ◽  
pp. 4786-4792 ◽  
Author(s):  
Xubin Zheng ◽  
Rongrong Zheng ◽  
Yi Hu ◽  
Jim Werngren ◽  
Lina Davies Forsman ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
René Rodríguez-Gutiérrez ◽  
Adrian Rendon ◽  
Maximiliano Barrera-Sánchez ◽  
Kevin Erick Gabriel Carlos-Reyna ◽  
Neri Alejandro Álvarez-Villalobos ◽  
...  

Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients’ health.Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion.Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment.Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2±3.6months) adrenocortical function was restored in all cases.Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat insufficient stimulated cortisol levels in the setting of MDR-TB.


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