Rifampicin-resistant tuberculosis (RR-TB) is largely underdetected in Indonesia. Xpert MTB/RIF (Xpert) has recently been introduced, prioritizing patients at risk of RR-TB, followed by phenotypic drug-susceptibility (DST) if rifampicin resistance is detected. This study investigated Xpert-based management of presumptive RR-TB cases under routine practice in West Java, Indonesia. We examined all records of patients tested with Xpert in the referral hospital for West Java in 2015–2016. We measured loss across a limited cascade of care, time to Xpert diagnosis and the commencement of initial second-line treatment, and identified factors associated with diagnostic and treatment delay. Additionally, we analyzed the appropriateness of treatment according to DST results. Of 3415 patients with presumptive RR-TB, 3215 (94%) were tested by Xpert, of whom 339 (10.5%) were diagnosed as RR-TB. 288 (85%) of 339 RR-TB patients started initial second-line TB treatment, with 48 (14%) patients being lost between diagnosis and pre-treatment assessment. Second-line treatment was commenced at a median of 41 days (IQR 29–70) after RR-TB diagnosis. Delays in both diagnosis and treatment initiation were observed in 104 (52%) of 201 RR-TB patients with identifiable referral date. Rural residence was associated with delay to diagnosis (adjusted OR 2.7; 95%CI 1.5–5.2) and treatment initiation (adjusted OR 2.0; 1.2–3.4). Of 162 patients with available DST result, 107 (66%) had multidrug-resistant tuberculosis (MDR-TB) and 32 (20%) had either pre-extensively drug resistant (pre-XDR) or extensively drug resistant tuberculosis (XDR-TB). We estimated that with the current algorithm 41% of pre-XDR or XDR-TB patients are diagnosed, and 33% of them started on an appropriate treatment regimen. Many patients with Xpert-diagnosed RR-TB either do not start MDR-TB treatment or encountered diagnostic and treatment delays under programmatic conditions in Indonesia, and most pre-XDR and XDR-TB cases remain undiagnosed. Further expansion and ongoing quality improvement of RR-TB services are urgently needed.

Drug-resistant tuberculosis (DR-TB) requires prolonged and complex therapy which is associated with several adverse drug reactions (ADR). The burden of ADR can affect the quality of life (QoL) of patients that consists of physical, mental, and social well-being, and influences the beliefs and behaviors of patient related to treatment. This article reviews the burden of ADR and its association with QoL and adherence. We used PubMed to retrieve the relevant original research articles written in English from 2011 to 2021. We combined the following keywords: “tuberculosis,” “Drug-resistant tuberculosis,” “Side Effect,” “Adverse Drug Reactions,” “Adverse Event,” “Quality of Life,” “Adherence,” “Non-adherence,” “Default,” and “Loss to follow-up.” Article selection process was unsystematic. We included 12 relevant main articles and summarized into two main topics, namely, 1) ADR and QoL (3 articles), and 2) ADR and therapy adherence (9 articles). The result showed that patients with ADR tend to have low QoL, even in the end of treatment. Although it was torturing, the presence of ADR does not always result in non-adherence. It is probably because the perception about the benefit of the treatment dominates the perceived barrier. In conclusion, burden of ADR generally tends to degrade QoL of patients and potentially influence the adherence. A comprehensive support from family, community, and healthcare provider is required to help patients in coping with the burden of ADR. Nevertheless, the regimen safety and efficacy improvement are highly needed.

Purpose: The coronavirus disease (COVID-19) outbreak has created a global health crisis. Secondary pulmonary bacterial infection is a COVID-19 complication, increasing morbidity and mortality. This study aimed to determine the pathogens, antibiotic susceptibility patterns, and risk factors for mortality in hospitalized COVID-19 patients. Patients and Methods: This retrospective study used secondary data from patients’ electronic medical records at Hasan Sadikin General Hospital and Santo Borromeus Hospital between March 2020 and March 2021. Overall, 2230 hospitalized COVID-19 patients were screened, and 182 of them who were hospitalized ≥ 48 hours with a procalcitonin level of ≥ 0.25 ng/mL were enrolled. Culture examination was performed on sputum samples to determine pathogen and antibiotic susceptibilities. Univariate and multivariate analyses were used to determine mortality-related risk factors in hospitalized COVID-19 patients. Results: The prevalence of secondary pulmonary bacterial infections in COVID-19 patients was 8.2%, with 161/182 pathogen growth from sputum samples. Mainly gram-negative bacteria (64.8%) were present, including Acinetobacter baumannii (31.9%), Klebsiella pneumoniae (19.8%), and Pseudomonas aeruginosa (8.8%). High rate of multidrug-resistant (MDR) pathogens was found among isolate (45.9%), ie carbapenem-resistance A.baumannii (CR-Ab) was 84.2%, extended-spectrum β-lactamase (ESBL) among K. pneumoniae was 61.1%. Secondary infection of MDR pathogens was associated with a higher risk of mortality (AOR 5.63, p = 0.001). Other associated factors were age ≥ 60 years, ventilator use, and female gender. Conclusion: Gram-negative bacteria are the predominant pathogens causing secondary pulmonary bacterial infection in COVID-19 patients, implying nosocomial infection. High resistance to first-line antimicrobial drugs was observed in Gram-negative bacteria and Gram-positive bacteria. High rate of MDR pathogens was found among isolate and was associated with a significant risk of mortality.

Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10–50 µL) within a few seconds (2–4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland–Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.

Multidrug-resistant tuberculosis (MDR-TB) is an infectious disease caused by Mycobacterium tuberculosis which is resistant to at least isoniazid and rifampicin. This disease is a worldwide threat and complicates the control of tuberculosis (TB). Long treatment duration, a combination of several drugs, and the adverse effects of these drugs are the factors that play a role in the poor outcomes of MDR-TB patients. There have been many studies with repurposed drugs to improve MDR-TB outcomes, including clofazimine. Clofazimine recently moved from group 5 to group B of drugs that are used to treat MDR-TB. This drug belongs to the riminophenazine class, which has lipophilic characteristics and was previously discovered to treat TB and approved for leprosy. This review discusses the role of clofazimine as a treatment component in patients with MDR-TB, and the drug’s properties. In addition, we discuss the efficacy, safety, and tolerability of clofazimine for treating MDR-TB. This study concludes that the clofazimine-containing regimen has better efficacy compared with the standard one and is also well-tolerated. Clofazimine has the potential to shorten the duration of MDR-TB treatment.

The metabolic system and immunology used to be seen as distinct fields of study. Recent developments in our understanding of how the immune system operates in health and disease have connected these fields to complex systems. An effective technique for identifying probable abnormalities of metabolic homeostasis brought on by disease is metabolomics, which is defined as the thorough study of small molecule metabolic intermediates within a biological system that collectively make up the metabolome. A prognostic metabolic biomarker with adequate prognostic accuracy for tuberculosis progression has recently been created. The rate-limiting host enzyme for the conversion of tryptophan to kynurenine, indoleamine 2,3-dioxygenase (IDO), is greatly elevated in the lungs of tuberculosis disease patients. Targeted study on tryptophan in tuberculosis disease indicates that such decreases may also resembled this upregulation. Although tuberculosis diagnosis has improved with the use of interferon release assay and tuberculosis nucleic acid amplification, tuberculosis control is made difficult by the lack of a biomarker to diagnose active tuberculosis disease. We hope that the reader of this work can develop an understanding of the advantages of metabolomics testing, particularly as a sort of testing that can be used for both diagnosing and monitoring a patient’s response to treatment for tuberculosis.