Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction:A case report and review of literature

BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.

Interferon-gamma release assays as a tool for differential diagnosis of gastrointestinal tuberculosis

In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.

psk1 virulence gene-induced pulmonary and systemic tuberculosis in a young woman with normal immune function:A case report

BACKGROUND Tuberculosis is a chronic infectious disease and an important public health pro-blem.Despite progress in controlling tuberculosis,the incidence of tuberculosis in China is still very high,with 895000 new cases annually.This case report des-cribes the investigation of a case of severe disseminated tuberculosis in a young adult with normal immune function,conducted to ascertain why a Mycobacterium tuberculosis(M.tuberculosis)strain caused such severe disease.CASE SUMMARY A previously healthy 28-year-old woman presented to our hospital with a 1-mo-nth history of fever and fatigue.She was diagnosed with severe disseminated pulmonary tuberculosis,spinal tuberculosis with paravertebral abscesses,and tuberculous meningitis.M.tuberculosis was isolated from bronchoal-veolar lavage fluid.She was treated with standard antituberculous therapy and underwent debridement,bone graft,and internal fixation surgery for spinal tuberculosis.She responded to therapy and regained her ability to walk following the surgery.We analysed the whole-genome sequence of the strain and designated it BLM-A21.Additional M.tuberculosis genomes were selected from the Virulence Factor Database(http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Mycobacterium)for comparison.An evolutionary tree of the BLM-A21 strain was built using PhyML maximum likelihood software.Further gene analysis revealed that,except for the pks1 gene,BLM-A21 had similar virulence genes to the CDC 1551 and H37Rv strains,which have lower dissemination.CONCLUSION We speculate that the pks1 virulence gene in BLM-A21 may be the key virulence gene responsible for the wide-spread dissemination of M.tuberculosis infection in this previously healthy adult with normal immune function.

Revisiting tuberculosis as a cause of gastric outlet obstruction:Insights from a case report

Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.

Perianal tuberculous ulcer with active pulmonary,intestinal and orificial tuberculosis:A case report

BACKGROUND Orificial tuberculosis is a rare type of tuberculosis,which is easy to be misdiagnosed,and can cause great damage to the perianal skin and mucosa.Early diagnosis can avoid further erosion of the perianal muscle tissue by tuberculosis bacteria.CASE SUMMARY Here,we report a case of disseminated tuberculosis in a 62-year-old male patient with a perianal tuberculous ulcer and active pulmonary tuberculosis,intestinal tuberculosis and orificial tuberculosis.This is an extremely rare case of cutaneous tuberculosis of the anus,which was misdiagnosed for nearly a year.The patient received conventional treatment in other medical institutions,but specific treatment was delayed.Ultimately,proper diagnosis and treatment with standard anti-tuberculosis drugs for one year led to complete cure.CONCLUSION For skin ulcers that do not heal with repeated conventional treatments,consider ulcers caused by rare bacteria,such as Mycobacterium tuberculosis.

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Recognizing and addressing the challenges of gastrointestinal tuberculosis

In this editorial,we comment on the article by Ali et al published in the recent issue of the World Journal of Clinical Cases.This case report shed light on a particularly rare manifestation of this disease-primary gastrointestinal tuberculosis(GTB)presenting as gastric outlet obstruction.GTB presents diagnostic challenges due to its nonspecific symptoms and lack of highly accurate diagnostic algorithms.This editorial synthesizes epidemiological data,risk factors,pathogenesis,clinical presentations,diagnostic methods,and therapies to raise awareness about GTB.GTB constitutes 1%-3%of all tuberculosis cases globally,with 6%-38%of patients also having pulmonary tuberculosis.Pathogenesis involves various modes of Mycobacterium tuberculosis complex entry into the gastrointestinal system,with the terminal ileum and ileocecal valve commonly affected.Clinical presentation varies,often resembling other intra-abdominal pathologies,necessitating a high index of suspicion.Diagnostic tools include a combination of biochemical,microbiological,radiological,and endoscopic assessments.Antitubercular medication remains the cornerstone of treatment,supplemented by surgical intervention in severe cases.Multidisciplinary management involving gastroenterologists,surgeons,pulmonologists,and infectious disease specialists is crucial for optimal outcomes.Despite advancements,timely diagnosis and management challenges persist,underscoring the need for continued research and collaboration in addressing primary GTB.

Primary extrapulmonary tuberculosis diagnosis warrants extraprecautious pulmonary tuberculosis exclusion workup

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis(an uncommon extrapulmonary tuberculosis condition)utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction.The diagnosis chiefly relied on high-end examinations,like computed tomography scans and histopathological evaluation of postoperatively resected bowel tissue,which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition.Given the geographic locations where the patient had been(and/or treated),pivotal consideration of tuberculosis-associated endemicities in those regions,like human immunodeficiency virus(HIV)infection,might have improved the case description.The obtainment of HIV-relevant histories,like intravenous drug use and sexual practice,are good places to start.The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radiohistopathological resemblance with pulmonary Mycobacterium tuberculosis.Altogether,this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative,comprehensive,systematic,and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Clinical effects of detailed nursing management interventions on medication adherence and disease perception in patients with drugresistant tuberculosis

BACKGROUND Tuberculosis(TB)is a chronic respiratory infectious disease that considerably jeopardizes human health,and there is no effective vaccine suitable for its prevention in the entire population.AIM To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant(DR-)TB using detailed nursing management.METHODS In total,114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study.Patients in the control group(n=57)were managed with conventional nursing care,while those in the observation group(n=57)were managed with detailed nursing care.Medication adherence,disease awareness scores,medication safety,and nursing satisfaction were compared between the two groups after the intervention.RESULTS The post-intervention medication compliance rate was 91.23%in the observation group and 75.44%in the control group,with the former being 15.79%higher than the latter(P<0.05).There was no statistically significant difference in the disease awareness scores between the two groups before the intervention;the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention(P<0.05).The incidence of gastrointestinal reactions,joint swelling and pain,hearing loss,electrolyte disorders,and liver and kidney function abnormalities were lower in the observation group than those in the control group.The total nursing satisfaction of the observation group was higher than that of the control group(P<0.05).CONCLUSION Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence,enhance awareness of the disease,ensure safety of medication,and improve satisfaction with nursing care.

Diabetes and tuberculosis:An emerging dual threat to healthcare

Tuberculosis(TB)remains a huge global healthcare challenge even in the 21^(st) century though the prevalence has dropped in developed countries in recent decades.Diabetes mellitus(DM)is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM.The coexistence of both diseases in the same individual also aggravates disease severity,complications,and chance of treatment failure because of gross immune alterations posed by DM as well as TB.Various complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and DM,some of which remain unknown even today.It is highly important to identify the risk factors for TB in patients with DM,and vice versa,to ensure early diagnosis and management to prevent complications from this ominous coexistence.In their research study published in the recent issue of the World Journal of Diabetes,Shi et al elaborate on the factors associated with the development of TB in a large cohort of DM patients from China.More such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

Organizing pneumonia secondary to pulmonary tuberculosis:A case report

BACKGROUND Organizing pneumonia secondary to pulmonary tuberculosis is rare.Moreover,the temporal boundary between pulmonary tuberculosis and secondary organizing pneumonia has not been defined.We report a case of secondary organizing pneumonia associated with pulmonary tuberculosis occurring after nine months of antituberculosis treatment.CASE SUMMARY A 54 years old man,previously diagnosed with pulmonary tuberculosis and tuberculous pleurisy,underwent nine months of antituberculosis treatment.Follow-up lung computed tomography revealed multiple new subpleural groundglass opacities in both lungs,and a lung biopsy confirmed organizing pneumonia.Treatment continued with anti-tuberculosis agents and hormone therapy,and subsequent dynamic pulmonary computed tomography exams demonstrated improvement in lesion absorption.No disease recurrence was observed after corticosteroid therapy discontinuation.CONCLUSION When treating patients with active pulmonary tuberculosis,if an increase in lesions is observed during anti-tuberculosis treatment,it is necessary to consider the possibility of tuberculosis-related secondary organizing pneumonia,timely lung biopsy is essential for early intervention.

Unveiling the Threat: Case Reports of Extra-Pulmonary Tuberculosis among Sanctuary Chimpanzees

Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.

Community Caregivers’ Experiences and Programmatic Strategies to Improve Active Case Finding in Community Tuberculosis Care in Botswana 2016-2021

Background: The community tuberculosis care program was started to reduce the impact of TB and increase successful treatment outcomes, thus contributing to meeting WHO targets on TB. According to the Botswana Ministry of Health, community tuberculosis care was introduced with the main goal of reducing tuberculosis-related morbidity and mortality among communities through the expansion of direct observed therapy and community involvement to community settings. The community caregivers were to support tuberculosis patients throughout their treatment period until they were cured or had completed their treatment. Settings: Two major cities of Botswana, Francistown and Gaborone, with more than twenty-two health clinics offering tuberculosis care. Objective: To investigate community caregivers’ experiences and identify programmatic strategies to improve active TB case findings under the community TB care (CTBC) program in Botswana during 2016-2021. Methods: We adopted a descriptive qualitative research design, followed by convenience purposive sampling. We obtained consent and interviewed 40 participants who met the inclusion criteria, 16 out of 73 in Gaborone and 24 out of 38 from Francistown. Results: We interviewed 40 caregivers with a mean age of 43.4 years. Accepting the caregiving role was identified as the main experience by more than two thirds of the caregivers. While at least more than two-fifth felt obligated to care for the patient at home due to personal relations. More than half of the respondents found caregiving difficult or frustrating due to some challenges encountered during the caregiving role. Behavioral modifications were suggested under different subthemes as strategies to improve active case finding. [-rId13-]Conclusion: Acceptance was the major experience in CTBC. Intensification of known programmatic strategies was suggested by caregivers to improve tuberculosis active case finding in CTBC.

INF-γ and IL-2 Profile as Therapeutic Markers in Tuberculosis Patients at the Jamot Hospital of Yaounde-Cameroon

Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment cannot permit to distinguish active ATB from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), secreted by activated T cells, is involved in immune response against Mycobacterium tuberculosis. This could be involved in the follow up of treatment response. The aim of our study was to determine IFN-γ and IL2 cytokines profiles of patients under antituberculosis treatment. Materials and Methods: A six months’ cross-sectional study was conducted at the Jamot Hospital of Yaoundé, from May to August 2021. Sociodemographic and clinical data as well as 5 mL of blood were collected from each participant. INF-γ and IL-2 were determined using indirect Enzyme linked Immuno-Sorbent Assay (ELISA) according to the manufacturer’s recommendations and spectrum exam in combination with radiography and GeneXpert were used as standard. P-values Results: The results showed that men were more infected 14/61 (31.8%) with a high presence in active and resistant TB groups. The mean age was 41.3 ± 13.1 years with a 95% CI = [38.2 - 44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6 ± 160.6 pg/mL and 26.6 ± 13.0 pg/mL in ATB patients, 251.1 ± 30.9 pg/mL and 21.4 ± 9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3 ± 93.3 pg/mL and 17.9 ± 9.4 pg/mL in cured patients, 15.1 ± 8.4 pg/mL and 5.3 ± 2.6 pg/mL in participants presumed healthy (p γ and IL-2rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful for the follow-up of anti-tuberculosis patients, particularly in the both cytokines association case.

Surgical Management of Mitral Valve Infective Endocarditis with Accidental Finding of Open Pulmonary Tuberculosis

Objective: This case report aimed to highlight intersections of TB and Cardiovasular diseases which carry high morbidity and mortality rates. Methods: We are reporting the surgical management of forty seven years female who had back ground history of IDDM (Insulin dependent diabetic Mellitus), ESRD (End stage renal disease) on HD (haemodialysis) also she had left subclavian artery stenosis, and paroxysmal atrial fibrillation. She was diagnosed with mitral valve infective endocarditis and found accidently to have an open pulmonary tuberculosis (TB) on the day before surgery. Results: She was started on first line anti-TB treatment. She was isolated in her private room and airborne precautions measures applied. The patient underwent a tissue Mitral Valve replacement and tricuspid valve repair annuloplasty. Special precautions were applied in Theatre and on cardiopulmonary bypass Machine guided by KAMC-J disinfection protocol. The patient made good recovery postoperatively. She was discharged well on day 7 post operatively. Conclusion: Intersections of TB and cardiovasular diseases carry high morbidity and mortality rates. Early diagnosis and early anti tuberculosis treatment can surely improve the patient prognosis. Our decontamination and disinfective procedures are recommended. Cases like this should be monitored long term for the development of further cardiovascular complication.

Prevalence of Latent Tuberculosis Infection [LTBI] in Prison Officers: A Systematic Review and Meta-Analysis

This study aimed to perform a systematic review and meta-analysis to determine the LTBI prevalence in prison officers worldwide. A systematic search was performed in PubMed, WoS, Embase, and BVS, including all articles related to LTBI prevalence and risk factors. After critical evaluation and qualitative synthesis of the identified articles, a meta-analysis was used. Five studies carried out between 2012 and 2022 were included, with a total sample size of 1718 prison officers. The overall LTBI prevalence was 50% [95% confidence interval [CI]: 48% - 52%;n = 816], with high heterogeneity between studies. Smoking [OR = 1.76;CI 95% = 1.26 - 2.46] and males [OR = 2.08;CI 95% = 1.31 - 3.31] were positively related to a higher LTBI prevalence among prison officers. Thus, preventive measures and the rapid and accurate diagnosis of new cases should be emphasized to ensure tuberculosis control, especially among risk groups such as prison officers.

Investigation of the Clinical Diagnostic Significance of the T-Cell Test for Tuberculosis combined with Erythrocyte Sedimentation Test in Pulmonary Tuberculosis

Objective:To investigate the clinical diagnostic significance of peripheral blood T-cell test(T-spot test)for tuberculosis(TB)infection combined with erythrocyte sedimentation rate(ESR)in pulmonary TB.Methods:41 patients with a clinical diagnosis of TB during hospitalization from January 2020 to April 2023 in our hospital were selected as the experimental group,and 45 patients without TB(bronchopneumonia patients)were selected as the control group.The diagnostic specificity,sensitivity,and accuracy of the T-spot TB test,ESR test,and the combined test of the two were calculated respectively.Results:The sensitivity,specificity,and accuracy of the T-spot TB test combined with ESR for the diagnosis of TB in the experimental group were significantly higher than the individual results of the T-spot TB test and ESR test alone(P<0.05).Conclusion:The T-spot TB test combined with the ESR test for TB diagnosis has greater clinical value than carrying out the tests individually.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.