Treatment Of Drug-resistant Tuberculosis Research Articles

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

BackgroundHepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.Case presentationThe 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.ConclusionEnhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China

BackgroundPretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug.MethodsTo investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020.ResultsWe observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes.ConclusionsOur results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Drug Targets, Current and Future Therapeutics for the Treatment of Multi Drug Resistant Tuberculosis with their Clinical Applications: A Critical Review

Abstract: Multi drug-resistant or extensive drug resistance Mycobacterium tuberculosis poses numerous challenges for health care workers and for public health authorities. Treating multidrug resistant or extensive drug resistance tuberculosis continues to be a difficult task, as a longer regimen is associated with a higher number of adverse drug events and economic burden and has a significant negative effect on health care resources. Many trials and observational studies were conducted. Few studies are underway to develop the universal regimen and improve the outcomes related to multi or extensive drug resistance tuberculosis with a shorter regimen duration. The current review will discuss which drug inhibits what target, their synthesis, genetic aspects, repurposed drugs, novel drugs, and extensive trials for the treatment of multi or extensive drug resistance tuberculosis.

Quantification of isoniazid in tablets for tuberculosis treatment by thin layer chromatography with smartphone image capture and ImageJ analysis

Isoniazid (INH) oral dosage tablets are an antibacterial medication commonly used to treat tuberculosis (TB). While this medication can be highly effective in managing and curing TB, manufacturing of poor-quality INH products can lead to the proliferation of drug resistant TB strains – particularly in low- and middle-income countries (LMICs). It is therefore imperative that reliable methods of quality screening of INH tablets are available for areas that have limited access to traditional testing resources. In this study, a thin layer chromatography (TLC) procedure for INH identification is validated in conjunction with smartphone image capture and open-source image analysis software to provide an alternative quantitative quality screening method for INH tablets, primarily intended for applications in LMICs. The method assessed two individual tablet formulations: 100 mg and 300 mg INH, each from different manufacturers. The modified TLC procedure used for the study was based on a validated high-performance thin layer chromatography method for the determination of rifampicin, INH, and pyrazinamide in a fixed dosage tablet. Quantitation was performed by visualizing and photographing TLC plates using a UV lamp, 3D-printed light box, and Apple iPhone SE 2nd Generation (2020) and Google Pixel 4a (5G) smartphones, and images were then analyzed using ImageJ Fiji software. The processed images’ pixel data were used to create a calibration curve from the INH standard spots to determine the concentration of an INH sample spot. Linearity, range, accuracy, repeatability and intermediate precision, specificity, and robustness were evaluated. The method was linear in the range of 0.150–0.450 mg mL−1, with coefficients of determination ≥0.98. The overall accuracy of the method was 99.2 % with an RSD of 2.4 % for image sets captured using the Apple iPhone, and 99.7 % with an RSD of 3.3 % for image sets captured using the Google Pixel. The pooled standard deviations for repeatability and intermediate precision were 2.27 % and 3.25 %, respectively, for the iPhone and 2.62 % and 3.74 %, respectively, for the Pixel. The method demonstrated sufficient specificity and robustness. The results of this method validation suggest that this procedure may provide a feasible alternative to traditional testing as a low-cost means of quality screening in LMICs.

Evaluating the biomolecular interaction between delamanid/formulations and human serum albumin by fluorescence, CD spectroscopy and SPR: Effects on protein conformation, kinetic and thermodynamic parameters

Delamanid is an anti-tuberculosis drug used for the treatment of drug-resistant tuberculosis. Since delamanid has a high protein bound potential, even patients with low albumin levels should experience high and rapid delamanid clearance. However, the interaction between delamanid and albumin should be better controlled to optimize drug efficacy. This study was designed to evaluate the binding characteristics of delamanid to human serum albumin (HSA) using various methods: fluorescence spectroscopy, circular dichroism (CD), surface plasmon resonance (SPR), and molecular docking simulation. The fluorescence emission band without any shift indicated the interaction was not affected by the polarity of the fluorophore microenvironment. The reduction of fluorescence intensity at 344nm was proportional to the increment of delamanid concentration as a fluorescence quencher. UV-absorbance measurement at the maximum wavelength (λmax, 280nm) was evaluated using inner filter effect correction. The HSA conformation change was explained by the intermolecular energy transfer between delamanid and HSA during complex formation. The study, which was conducted at temperatures of 298K, 303K, and 310K, revealed a static quenching mechanism that correlated with a decreased of bimolecular quenching rate constant (kq) and binding constant (Ka) at increased temperatures. The Ka was 1.75–3.16 × 104M−1 with a specific binding site with stoichiometry 1:1. The negative enthalpy change, negative entropy change, and negative Gibbs free energy change demonstrated an exothermic-spontaneous reaction while van der Waals forces and hydrogen bonds played a vital role in the binding. The molecular displacement approach and molecular docking confirmed that the binding occurred mainly in subdomain IIA, which is a hydrophobic pocket of has, with a theoretical binding free energy of −9.33kcal/mol. SPR exhibited a real time negative sensorgram that resulted from deviation of the reflex angle due to ligand delamanid-HSA complex forming. The binding occurred spontaneously after delamanid was presented to the HSA surface. The SPR mathematical fitting model revealed that the association rate constant (kon) was 2.62 × 108s−1M−1 and the dissociation rate constant (koff) was 5.65 × 10−3 s−1M−1. The complexes were performed with an association constant (KA) of 4.64 × 1010 M−1 and the dissociation constant (KD) of 2.15 × 10−11 M. The binding constant indicated high binding affinity and high stability of the complex in an equilibrium. Modified CD spectra revealed that conformation of the HSA structure was altered by the presence of delamanid during preparation of the proliposomes that led to the reduction of secondary structure stabilization. This was indicated by the percentage decrease of α-helix. These findings are beneficial to understanding delamanid-HSA binding characteristics as well as the drug administration regimen.

Epidemiology and outcomes of drug-resistant tuberculosis cases notified in a low-resource district in Kerala, India 2017–2021 – A 5-year retrospective analysis

Objectives: Kasaragod district reports the highest drug-resistant tuberculosis (DR-TB) case notification rates in Kerala. We conducted a cross-sectional study in Kasaragod to describe the DR-TB cases notified from January 2017 to December 2021 and to identify the factors associated with unfavorable treatment outcomes in DR-TB patients. Materials and Methods: We analyzed the programmatic data from the “Nikshay portal” (a web-based patient management information system for [TB] under the National TB Elimination Program), DR-TB treatment cards, and treatment registers available with the district TB center for all the DR-TB patients notified during the study period. We described the DR-TB cases by year, local self-government area (the local administrative setup), age, gender, income level, and treatment outcomes. We compared sociodemographic, anthropometric, and clinical factors among the DR-TB patients with favorable (cured and treatment completed) and unfavorable (died, lost to follow-up, and treatment failure) treatment outcomes. Results: From January 2017 to December 2021, 128 DR-TB cases were notified from Kasaragod. Annual notification rates varied from 1.4 to 3.4/100,000 population with the highest notification in 2019. The proportion of new TB cases notified tested for drug sensitivity rose from 22% in 2017 to 86% in 2021. Seven of 41 local self-government areas had not notified DR-TB cases during 2017–2021. The notification was higher in inter-state border areas and the coastal belt of the district. The notification of DR-TB cases was highest among the 45–59 age group (17/100,000), followed by the 60 above group (11/100,000). Males and those living below the poverty line had higher notification rates. Among the outcomes evaluated 118 DR-TB patients, 89 (75.4%) had favorable outcomes, whereas the remaining 24.6% had unfavorable outcomes (death 18 [15.3%], loss to follow-up 7 [6%], and treatment failure 4 [3.4%]). Age more than 45 years adjusted odds ratio (aOR) 3.1 (95% confidence interval [CI] 1.1–8.8), income category below the poverty line aOR 6 (95% CI 1.2–28.6), admitted at least twice during treatment aOR 9.2 (95% CI 2.8–30.3), and body mass index at diagnosis <18.5 kg/m2 aOR 3 (95% CI 1.1–10.3) were found to be significantly associated with unfavorable treatment outcomes. Conclusion: DR-TB notifications have increased in the Kasaragod district from 2017 to 2021, with a high burden among males aged 45 years and above. The favorable treatment outcome is better than the national and state average. Regular monitoring and follow-up of multidrug-resistant patients with low incomes, above 45 years, and underweight may improve the final treatment outcomes.

Discordance in Phenotypic and Genotypic Susceptibility Testing for Streptomycin Due to Nonsynonymous/Nonsense/Deletion Frame-Shift Mutations in gidB among Clinical Mycobacterium tuberculosis Isolates in Kuwait

Objective: Increasing reports of resistance to newer antituberculosis drugs have prompted the search for other alternative drugs. Streptomycin (STR) could be used for the treatment of drug-resistant tuberculosis if susceptibility of Mycobacterium tuberculosis isolate to STR could be accurately detected. We performed phenotypic and genotypic drug susceptibility testing (DST) of 118 M. tuberculosis isolates for STR. Materials and Methods: Fifty pansusceptible and 68 multidrug-resistant M. tuberculosis (MDR-TB) isolates were used. Phenotypic DST for STR, rifampicin, isoniazid, and ethambutol was performed by mycobacteria growth indicator tube 960 System. Genotypic DST was done by GenoTypeMTBDRplus assay for rifampicin and isoniazid and by PCR-sequencing of rpsL, rrs, and gidB genes for STR. MDR-TB isolates were genotyped by spoligotyping. Results: Phenotypic DST identified 50 isolates susceptible to all four drugs (pansusceptible). Sixty-one of 68 MDR-TB isolates were resistant to STR. Genotypic testing for rifampicin and isoniazid yielded expected results. Fifty pansusceptible and 7 STR-susceptible MDR-TB isolates contained no mutation in rpsL or rrs, while 47, 2, and 1 STR-resistant isolate contained rpsL, rrs, and rpsL + rrs mutations, respectively. Of the remaining 11 STR-resistant MDR-TB, 9 isolates contained deletion frame-shift/nonsynonymous mutations in gidB. Surprisingly, 13 pansusceptible isolates also contained deletion frame-shift/nonsense/nonsynonymous mutations in gidB. Also, 30 of 68 MDR-TB but only 2 of 50 pansusceptible isolates belonged to the Beijing genotype. Conclusions: Our data show that, like rifampicin, ethambutol, and pyrazinamide, STR also exhibits discordant phenotypic and genotypic DST results for some M. tuberculosis isolates. Hence, STR should be included in therapy regimens only if both phenotypic and genotypic resistance testing indicate susceptibility to avoid amplification of resistance and drug toxicity.

QT-Interval Prolongation in the Treatment of Drug-Resistant Tuberculosis

The review analyzes the research articles, guidelines, and clinical trial results on the effect of fluoroquinolones, bedaquiline, nitroimidazoles, and clofazimine on QTc prolongation. The importance of timely and regular monitoring of cardiotoxicity and the importance of continuing clinical trials for the discovery of anti-tuberculosis drugs with a satisfactory safety profile are presented.

Multidrug-resistant tuberculosis.

Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid. Collectively, these subgroups are referred to as drug-resistant TB (DR-TB). All forms of DR-TB can be as transmissible as rifampicin-susceptible TB; however, it is more difficult to diagnose, is associated with higher mortality and morbidity, and higher rates of post-TB lung damage. The various forms of DR-TB often consume >50% of national TB budgets despite comprising <5-10% of the total TB case-load. The past decade has seen a dramatic change in the DR-TB treatment landscape with the introduction of new diagnostics and therapeutic agents. However, there is limited guidance on understanding and managing various aspects of this complex entity, including the pathogenesis, transmission, diagnosis, management and prevention of MDR-TB and XDR-TB, especially at the primary care physician level.

Strategy of the Host-Directed Therapy for Tuberculosis: the Importance of Interferon-Gamma in the Pathogenesis and Therapy of Tuberculosis Infection

The review analyzes of 69 publications and discusses treatment of drug-resistant tuberculosis from the standpoint of the influence on immune mechanisms that limit progression of inflammation and damage to lung tissue. Interferon-gamma is the most significant cytokine in tuberculosis infection pathogenesis. The article describes genotypic and phenotypic features of interferon-gamma production in various clinical forms of pulmonary tuberculosis. It presents the data supporting the therapeutic use of recombinant interferon-gamma and results of its clinical use as adjuvant treatment additionally to chemotherapy. It demonstrates the prospects for immunotherapy with Ingaron, the drug manufactured in Russia, for patients with multiple drug-resistant pulmonary tuberculosis.

IDF23-0433 The effect of diabetes on mortality during drug-resistant tuberculosis treatment: a study from Indonesia

IDF23-0433 The effect of diabetes on mortality during drug-resistant tuberculosis treatment: a study from Indonesia

Drug-Resistant Tuberculosis: Development Mechanisms and Methods of Molecular Genetic Diagnosis

The widespread occurrence of drug-resistant tuberculosis is an important public health challenge. To better understand this phenomenon, the article summarizes current ideas on the development of mechanisms of Mycobacterium tuberculosis resistance to antituberculosis drugs. Special attention is paid to the mechanism of acquired resistance based on mutations in the genes encoding antituberculosis drug targets or enzymes that translate pro-drug into its active form; the effect of these mutations on fitness of the pathogen is in the focus of the article. It emphasizes the leading role of molecular genetic methods for diagnosing M. tuberculosis drug resistance and importance of these methods for preventing the expansion of the pathogen’s resistance range and the spread of resistant clones in the population. A comparison of sequencing and PCR-based methods capacities led to a conclusion that at the current stage of technological development it is reasonable to use each of these approaches for specific purposes: domestic PCR-based tests — for diagnosis, and sequencing — for basic research of M. tuberculosis evolution and epidemiological monitoring. Promising areas of M. tuberculosis resistance research were proposed to develop new approaches for diagnosis and treatment of drug-resistant tuberculosis and to provide effective personalized therapy.

Why do patients with DR-TB do not complete their treatment? Findings of a qualitative study from Pakistan

BackgroundOne of the major reasons for unsuccessful treatment outcomes among patients with drug-resistant tuberculosis (DR-TB) is the high rate of loss to follow-up (LTFU). However, in Pakistan, no qualitative study...

T-wave morphology abnormalities in the STREAM stage 1 trial

ABSTRACT Background Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation. Research design and methods STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1–4), and late (weeks 12–36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate). Results Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25). Conclusions T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment. Trial Registration The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190

Usability of simplified audiometry and electrocardiogram during treatment of drug-resistant tuberculosis in Mozambique: a qualitative study

BackgroundIn 2021, there were approximately 450,000 cases of drug-resistant tuberculosis (DR-TB) worldwide. The treatment of DR-TB historically included expensive and toxic injectable drugs leading to adverse effects including ototoxicity and Electrocardiogram (ECG) abnormalities. This study described the perspectives of healthcare providers and people with DR-TB on the usability of simplified audiometry and ECG for monitoring treatment adverse effects.MethodsA qualitative study was conducted in December 2019 across four provinces in Mozambique, namely Maputo, Gaza, Zambézia, and Nampula. Sixteen outpatient primary care health facilities equipped with simplified Audiometry and/or ECG devices (specifically, SHOEBOX Audiometer® and/or SmartHeart Pro ECG®) installed for at least 6 months before the study initiation were selected. The data was collected using in-depth interviews (IDI) and Focus Group Discussions (FGD) techniques. Interviews were audio-recorded, transcribed verbatim in Portuguese, coded, and analyzed using Nvivo 12 software®. We generated two themes and fit our results into a conceptual framework consisting of three domains in the implementation of technological innovations in health.ResultsA total of 16 healthcare providers and 91 people undergoing treatment for DR-TB were enrolled in the study. Most people with DR-TB had experienced audiometry testing and demonstrated a good understanding of the assessments. Conversely, while most healthcare providers demonstrated robust knowledge of the importance of both audiometry and ECG assessments, they were not confident in managing ECG devices and interpreting the results.ConclusionsWhile healthcare providers demonstrated a consolidated understanding of the importance of audiometry, the limited number of devices and lack of training were constraints, impeding optimal usage and service delivery.

Gaps in the Diagnosis and Treatment of Drug-resistant Tuberculosis in Mexico

Objective: The study aimed to determine the critical gaps in the care of drug-resistant tuberculosis to implement strategies for its elimination. Material and Methods: Cases with various resistance profiles that were presented to the National Advisory Group for Drug Resistance during the years 2019-2022 have been described. Results and Discussion: 104 cases were included in this study. 41% of the patients had diabetes (41%) as a comorbidity. There have been observed delays in the reporting of rapid molecular tests; with the Xpert MTB/RIF, delays of 6.33 days have been reported. There have also been observed delays in the request for phenotypic drug susceptibility tests; from the time of initial diagnosis, patients have been found to receive their first drug susceptibility test, on average, after 20 months. The bacteriological follow-up during the treatment with monthly culture has been found to only be carried out in 8% of the cases. In the contact investigation, only 16% of the listed contacts had been studied for infection or active disease. Conclusion: The elimination of these gaps requires the decentralization of susceptibility tests for fluoroquinolones, shortening the times between the diagnosis of drug resistance and the start of treatment, a close clinical and bacteriological follow-up, and an exhaustive investigation of contacts.

Global adoption of 6-month drug-resistant TB regimens: Projected uptake by 2026.

The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3-4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time. Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs. Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients. The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study.

The emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia. A cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus and MTBDRsl assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations. Of the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1 (S315T1) (20, 76.9%) and rpoB (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1 gene, and the other had missing gyrA WT1, gyrA WT3, and rrs WT1 genes without any mutation. The detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.

Infections in Pregnancy

Abstract Infections in pregnant women tend to be more severe and pose unique treatment challenges. After all, the well-being of two individuals is at stake. Screening all pregnant women in early pregnancy for bacteriuria is recommended. Pyelonephritis and puerperal sepsis should be managed aggressively with appropriate empiric antibiotic choices. Increasing resistance in Enterobacterales is the complicating treatment of both these illnesses in the Indian setting. Influenza can lead to serious maternal and fetal outcomes; early empiric antiviral therapy and universal maternal vaccination are important. Dengue is an important cause of fever in pregnant women and can complicate vaginal and operative delivery due to thrombocytopenia. Falciparum malaria can now be treated with artemisinin-based combination therapy (ACT) in all trimesters. The drug of choice for scrub typhus is azithromycin; a combination of doxycycline and azithromycin can be considered in very severe disease. Treatment of both drug-sensitive and drug-resistant tuberculosis in pregnancy is similar to the nonpregnant. Safety data relating to bedaquiline and delamanid from animal models and cohort studies are reassuring.