The spectrum of adverse events in the treatment of multidrug-resistant tuberculosis among people receiving antiretroviral therapy

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

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Epidemiological analysis of factors influencing the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-eao-1504 ◽

2021 ◽

Vol 11 (5) ◽

pp. 989-993

Author(s):

A. V. Kukurika ◽

E. I. Yourovskaya ◽

V. A. Lyakhimets

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Viral Hepatitis ◽

Combined Treatment ◽

Miliary Tuberculosis ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Viral Hepatitis C ◽

Cd4 Lymphocytes

The epidemiological significance of combined forms of especially dangerous infections has not been studied enough, unlike mono-infections. Currently, there is a tendency towards an increase in the incidence of multidrug-resistant tuberculosis. The formation of severe forms of the disease is caused by other widespread infections, such as chronic viral hepatitis and HIV. Polymorbid conditions distort the clinical manifestations of tuberculosis, reduce the effectiveness of anti-tuberculosis therapy and worsen the prognosis of the disease. Risk factors among patients in this category need analysis to carefully monitor patients and ensure infection control. Objective is to analyze the factors affecting the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis. Materials and methods. Cases of the combined pathology of multiresistant tuberculosis, HIV infection and viral hepatitis with a dominant diagnosis of tuberculosis are analyzed. Results and discussion. The influence of the immunological status on the course of combined pathology was revealed. Since all the patients under study had clinical stage 4 of HIV infection, tuberculosis developed as an opportunistic infection. Severe immunosuppression (CD4 < 200 cells/ml) contributed to the progression of the generalized tuberculosis process. Long-term immunodeficiency was an unfavorable factor; in the overwhelming majority of cases, antiretroviral therapy was prescribed only after tuberculosis was detected. The dependence of the clinical form of tuberculosis on the level of CD4-lymphocytes was noted: isolated lesion of the chest organs prevailed in patients with a level of CD4-lymphocytes more than 200 cells/ml, generalization of TB process — with CD4 less than 200 cells/ml. Patients with miliary tuberculosis had a higher mortality rate compared to patients with other clinical forms, regardless of antiretroviral therapy. It was revealed that socially disoriented young people with viral hepatitis C prevailed in the structure of patients, the prevalence of which was due to the influence of aggravating factors, such as alcohol and drug abuse, and stay in prisons. Against the background of combined treatment, there was no significant effect of viral hepatitis on the course of polymorbid conditions and the effectiveness of the therapy.

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Neuropsychiatric reactions induced by cycloserine in the treatment of multidrug-resistant tuberculosis: what an Indian female patient tells us

BMJ Case Reports ◽

10.1136/bcr-2019-230993 ◽

2019 ◽

Vol 12 (12) ◽

pp. e230993 ◽

Cited By ~ 2

Author(s):

Enrica Intini ◽

Girija Kishore ◽

Luca Richeldi ◽

Zarir F Udwadia

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Health Crisis ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Group B

Multidrug-resistant tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people affected by drug-resistant tuberculosis. To implement tuberculosis control, in 2018, WHO recommended cycloserine as one of the Group B drugs. Following this recommendation, cycloserine should be generally included in the starting line-up in the longer regimen for the treatment of multidrug-resistant tuberculosis. However, neurological toxicity associated with this drug concerns clinicians and limits its use. In this paper, we present a case of a 48-year-old woman with a diagnosis of multidrug-resistant tuberculosis treated with cycloserine, who developed psychiatric adverse events after 3 months of administration. This case shows the need for close psychiatric follow-up to promptly detect adverse events in patients receiving regimens for multi-drug resistant tuberculosis.

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Adverse Events Associated With the Treatment of Multidrug-Resistant Tuberculosis

American Journal of Therapeutics ◽

10.1097/01.mjt.0000433951.09030.5a ◽

2016 ◽

Vol 23 (2) ◽

pp. e521-e530 ◽

Cited By ~ 37

Author(s):

Shanshan Wu ◽

Yuelun Zhang ◽

Feng Sun ◽

Mingting Chen ◽

Lin Zhou ◽

...

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Doing No Harm? Adverse Events in a Nation-Wide Cohort of Patients with Multidrug-Resistant Tuberculosis in Nigeria

PLoS ONE ◽

10.1371/journal.pone.0120161 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0120161 ◽

Cited By ~ 16

Author(s):

Yohanna Kamabi Avong ◽

Petros Isaakidis ◽

Sven Gudmund Hinderaker ◽

Rafael Van den Bergh ◽

Engy Ali ◽

...

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Adverse Events Associated with Treatment of Multidrug-Resistant Tuberculosis in China: An Ambispective Cohort Study

Medical Science Monitor ◽

10.12659/msm.904682 ◽

2017 ◽

Vol 23 ◽

pp. 2348-2356 ◽

Cited By ~ 11

Author(s):

Yang Zhang ◽

Shanshan Wu ◽

Yinyin Xia ◽

Ni Wang ◽

Lin Zhou ◽

...

Keyword(s):

Cohort Study ◽

Adverse Events ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis

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Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis

European Respiratory Journal ◽

10.1183/13993003.01799-2016 ◽

2016 ◽

Vol 49 (3) ◽

pp. 1601799 ◽

Cited By ~ 58

Author(s):

Lorenzo Guglielmetti ◽

Marie Jaspard ◽

Damien Le Dû ◽

Marie Lachâtre ◽

Dhiba Marigot-Outtandy ◽

...

Keyword(s):

Adverse Events ◽

Multidrug Resistant ◽

Favourable Outcome ◽

Serious Adverse Events ◽

Term Outcome ◽

Long Term Outcome ◽

Cardiac Side Effects ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.

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