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Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14060

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Special Issue Editor

Dr. Matt D. Johansen

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Guest Editor

Centre for Inflammation, Centenary Institute & University of Technology Sydney, Missenden Rd, Camperdown, NSW 2050, Australia
Interests: mycobacteria; host-pathogen interactions; antimicrobial resistance; diagnostics

Special Issue Information

Dear Colleagues,

It is estimated that approximately 1 billion people are currently infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Moreover, the incidence of infections with non-tuberculous mycobacteria (NTM) is exponentially increasing, frequently surpassing new TB infections in developed countries. Collectively, TB and NTM infections represent a significant global healthcare crisis which is further exacerbated by the increased emergence of multidrug resistance and the lack of novel therapies.

In this Special Issue of Antibiotics, we are seeking original research articles, short communications, reviews, case reports, and perspectives that cover but are not limited to the following topics:

Control measures to combat TB and NTM infections;
Diagnosis for the identification of TB and NTM infection;
Novel antimicrobial therapies and new therapeutic drug targets;
Mechanisms of antimicrobial resistance in TB and NTM species;
New cellular and animal models to examine the efficacy of antimicrobial therapies against TB and NTM infections.

Dr. Matt D. Johansen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

mycobacteria
tuberculosis
non-tuberculous mycobacteria
antimicrobial
drug resistance
novel therapies

Published Papers (6 papers)

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Research

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11 pages, 546 KiB

Open AccessArticle

Screening for Tuberculosis Infection among Migrants: A Cost-Effectiveness Analysis in the Italian Context

by Giulia Russo, Valentina Marchese, Beatrice Formenti, Claudia Cimaglia, Gianluca Di Rosario, Irene Cristini, Paola Magro, Issa El-Hamad, Daniela Maria Cirillo, Enrico Girardi and Alberto Matteelli

Antibiotics 2023, 12(4), 631; https://doi.org/10.3390/antibiotics12040631 - 23 Mar 2023

Viewed by 1194

Abstract

Background: Screening of tuberculosis infection (TBI) among migrants from high-incidence countries is a cornerstone of tuberculosis control in low-incidence countries. However, the optimal screening strategy has not been defined yet. Methods: A quasi-experimental study involving migrants residing in the province of Brescia was carried out that aimed at assessing the completion rate, time to completion, preventive treatment initiation rate, and cost-effectiveness of two strategies for TBI screening. They underwent TBI screening with the IGRA-only strategy (arm 1) or with the sequential strategy (tuberculin skin test, TST, followed by IGRA in case of a positive result—arm 2). The two strategies were compared in terms of screening completion, time to complete the screening process, therapy initiation, and cost-effectiveness. Results: Between May 2019 and May 2022, 657 migrants were evaluated, and 599 subjects were included in the study, with 358 assigned to arm 1 and 237 to arm 2. Screening strategy was the only factor associated with screening completion in a multivariable analysis, with the subjects assigned to the IGRA-only strategy more likely to complete the screening cascade (n = 328, 91.6% vs. n = 202, 85.2%, IRR 1.08, 95% CI (1.01–1.14), p = 0.019). The time to complete the screening process was significantly longer for patients assigned to the sequential strategy arm (74 days vs. 46 days, p = 0.002). Therapy initiation did not significantly differ between the two arms, and cost-effectiveness was higher for the sequential strategy. Conclusion: Sequential strategy implementation for TBI screening among migrants may be justified by its higher cost-effectiveness in spite of the lower completion of the screening cascade. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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8 pages, 919 KiB

Open AccessCommunication

Perchlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis

by Anastasia Ushtanit, Yulia Mikhailova, Ludmila Krylova, Dmitry Grigorash, Marina Makarova, Svetlana Safonova and Danila Zimenkov

Antibiotics 2023, 12(3), 590; https://doi.org/10.3390/antibiotics12030590 - 15 Mar 2023

Viewed by 1380

Abstract

The emergence of drug-resistant tuberculosis forced the development of new drugs and the screening of more effective or less toxic analogues. Mycolic acid biosynthesis is targeted by several antituberculosis drugs, isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in the FAS-II cycle, was officially approved for tuberculosis treatment in the Russian Federation and was included in the Russian national clinical guidelines. Using the serial dilution method on 7H10 agar plates for perchlozone and a Sensititre MYCOTB microdilution plate, we analyzed the phenotypic properties of primary clinical isolates of M. tuberculosis and analyzed the molecular determinants of resistance to isoniazid, ethionamide, and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between ethionamide and perchlozone was driven by mutations in the ethA gene encoding monooxygenase responsible for the activation of both drugs. The presumably susceptible to perchlozone and wild-type strains had MICs ranging from 2 to 4 mg/L, and the breakpoint was estimated to be 4 or 8 mg/L. In conclusion, susceptibility to perchlozone is retained for a part of the MDR strains, as is susceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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11 pages, 2655 KiB

Open AccessArticle

Increased Susceptibility of Mycobacterium tuberculosis to Ethionamide by Expressing PPs-Induced Rv0560c

by Hoonhee Seo, Sukyung Kim, Hafij Al Mahmud, Omme Fatema Sultana, Youngkyoung Lee, Youjin Yoon, Md Abdur Rahim, Sujin Jo, Jiwon Choi, Saebim Lee and Ho-Yeon Song

Antibiotics 2022, 11(10), 1349; https://doi.org/10.3390/antibiotics11101349 - 04 Oct 2022

Viewed by 1416

Abstract

Tuberculosis, an infectious disease, is one of the leading causes of death worldwide. Drug-resistant tuberculosis exacerbates its threat. Despite long-term and costly treatment with second-line drugs, treatment failure rates and mortality remain high. Therefore, new strategies for developing new drugs and improving the efficiency of existing drug treatments are urgently needed. Our research team reported that PPs, a new class of potential anti-tuberculosis drug candidates, can inhibit the growth of drug-resistant Mycobacterium tuberculosis. Here, we report a synergistic effect of PPs with ethionamide (ETH), one of the second-line drugs, as a result of further research on PPs. While investigating gene expression changes based on microarray and 2DE (two-dimensional gel electrophoresis), it was found that PPs induced the greatest overexpression of Rv0560c in M. tuberculosis. Based on this result, a protein microarray using Rv0560c protein was performed, and it was confirmed that Rv0560c had the highest interaction with EthR, a repressor for EthA involved in activating ETH. Accordingly, a synergistic experiment was conducted under the hypothesis of increased susceptibility of ETH to M. tuberculosis by PPs. As a result, in the presence of 0.5× MIC PPs, ETH showed a growth inhibitory effect on drug-sensitive and -resistant M. tuberculosis even at a much lower concentration of about 10-fold than the original MIC of ETH. It is also suggested that the effect was due to the interaction between PPs and Rv2887, the repressor of Rv0560c. This effect was also confirmed in a mouse model of pulmonary tuberculosis, confirming the potential of PPs as a booster to enhance the susceptibility of M. tuberculosis to ETH in treating drug-resistant tuberculosis. However, more in-depth mechanistic studies and extensive animal and clinical trials are needed in the future. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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9 pages, 1720 KiB

Open AccessArticle

Anti-Tuberculosis Activity of Three Carbapenems, Clofazimine and Nitazoxanide Using a Novel Ex Vivo Phenotypic Drug Susceptibility Model of Human Tuberculosis

by Ximena Gonzalo, Magdalena K. Bielecka, Liku Tezera, Paul Elkington and Francis Drobniewski

Antibiotics 2022, 11(10), 1274; https://doi.org/10.3390/antibiotics11101274 - 20 Sep 2022

Viewed by 1615

Abstract

We evaluated a novel physiological 3-D bioelectrospray model of the tuberculosis (TB) granuloma to test the activity of a known anti-TB drug, clofazimine; three carbapenems with potential activity, including one currently used in therapy; and nitazoxanide, an anti-parasitic compound with possible TB activity (all chosen as conventional drug susceptibility was problematical). PBMCs collected from healthy donors were isolated and infected with M. tuberculosis H37Rv lux (i.e., luciferase). Microspheres were generated with the infected cells; the anti-microbial compounds were added and bacterial luminescence was monitored for at least 21 days. Clavulanate was added to each carbapenem to inhibit beta-lactamases. M. tuberculosis (MTB) killing efficacy was dose dependent. Clofazimine was the most effective drug inhibiting MTB growth at 2 mg/L with good killing activity at both concentrations tested. It was the only drug that killed bacteria at the lowest concentration tested. Carbapenems showed modest initial activity that was lost at around day 10 of incubation and clavulanate did not increase killing activity. Of the carbapenems tested, tebipenem was the most efficient in killing MTB, albeit at a high concentration. Nitazoxanide was effective only at concentrations not achievable with current dosing (although this might partly have been an artefact related to extensive protein binding). Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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16 pages, 3838 KiB

Open AccessArticle

A Global Bibliometric Analysis on Antibiotic-Resistant Active Pulmonary Tuberculosis over the Last 25 Years (1996–2020)

by Md Asiful Islam, Shoumik Kundu, Tengku Muhammad Hanis, Khalid Hajissa and Kamarul Imran Musa

Antibiotics 2022, 11(8), 1012; https://doi.org/10.3390/antibiotics11081012 - 27 Jul 2022

Cited by 7 | Viewed by 1883

Abstract

Background: Tuberculosis (TB) is still a leading global cause of mortality and an increasingly crucial problem in fighting TB is antibiotic resistance. We aimed to conduct a bibliometric analysis on the articles of the past 25 years on antibiotic-resistant active pulmonary TB. Methods: Appropriate keywords were combined using the Boolean and wildcard operators and searched in Scopus database for articles published between 1996 and 2020 in English language. For all the bibliometric analyses, the Bibliometrix package in RStudio and Biblioshiny web apps were used. We identified the publication and citation trends, topmost cited documents, most productive authors, countries and institutions and most influential journals and funding agencies. We constructed collaborative networks of countries and co-citations. In addition, we developed a Three-Fields plot and a Thematic Map to explore different publication themes. Results: We included 7024 articles (88.9% research articles) and a persistently increasing publication and citation trends were evident throughout the past 25 years. Boehme 2010 was the most cited paper (1609 times cited), Stefan Niemann was the most productive author (86 papers), and ‘International Journal of Tuberculosis and Lung Disease’ was the leading journal. Centers for Disease Control and Prevention was the top contributing institution (3.7% papers) and both US- and UK-based funders were leading. The most productive countries were the USA, India, the UK, South Africa, and China and most of the collaborations took place between the USA, the UK, and South Africa. Conclusion: Undoubtedly, researchers and funders from the USA dominated followed by the UK in most of the fields in antibiotic-resistant TB research. The outcomes of antibiotic-resistant TB research would be more productive and translational if researchers from low- or middle-income countries (especially from Africa, South America and Asia) with high research productivity and TB burden could be in collaboration with high-income countries exhibiting low TB burden. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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7 pages, 2018 KiB

Open AccessCase Report

Granulomatous Cheilitis or Tuberculid?

by Georgi Tomov, Parvan Voynov and Svitlana Bachurska

Antibiotics 2022, 11(4), 522; https://doi.org/10.3390/antibiotics11040522 - 14 Apr 2022

Cited by 1 | Viewed by 5825

Abstract

The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, an infection by Mycobacterium tuberculosis (MBT) should be considered. In such cases, the GC could be the clinical presentation of a tuberculid resulting from a hypersensitivity reaction to an underlying focus of active (ATBI) or latent tuberculosis infection (LTBI). This communication describes an immunocompetent patient diagnosed with GC resulting from tuberculid, who responded well to Isoniazid monotherapy. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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