Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation

Ahmed, Sultan; Raqib, Rubhana; Guðmundsson, Guðmundur H.; Bergman, Peter; Agerberth, Birgitta; Rekha, Rokeya Sultana

doi:10.3390/antibiotics9010021

Cited by 30 publications

(17 citation statements)

References 154 publications

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“…The goal of host-directed therapies is to modulate immune mechanisms that relieve exaggerated inflammation to reduce lung tissue damage. 4 Metformin, a most commonly used medication for type 2 diabetes, was proposed to be a candidate for host-directed therapy for COVID-19 to reduce mortality. 5 However, its efficacy remains to be validated.…”

Section: Introductionmentioning

confidence: 99%

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

Luo

Qiu

Liu

et al. 2020

The American Journal of Tropical Medicine and Hygiene

224

222

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. Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin, P = 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%), P = 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.

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Section: Introductionmentioning

confidence: 99%

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

Luo

Qiu

Liu

et al. 2020

The American Journal of Tropical Medicine and Hygiene

224

222

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“…CRP seems not to be conclusive as a singular TB diagnosis marker, but successful in facilitating systematic TB screening, when associated with the gold-standard reference method or GeneXpert assay, within HIV-positive groups [31]. This is the reason why the evaluation of CRP as a screening biomarker for active PTB has been widely analysed and argued by researchers in the past years [14,16,29,31,34,35] especially since the majority of the infected individuals, children and adults are diagnosed with PTB [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Screening Performance of C-Reactive Protein for Active Pulmonary Tuberculosis in HIV-Positive Patients: A Meta-analysis

Meca

Bogdan

Turcu-Știolică

et al. 2020

Preprint

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Background: Tuberculosis (TB) is the leading infectious cause of mortality worldwide. In the last years, resistant strains of the etiological agent, Mycobacterium tuberculosis, have emerged, thus demanding more triage tests to identify active pulmonary TB (PTB) patients and to evaluate their disease severity. Therefore, acute-phase reaction serum tests are required for monitoring TB patients, among WHO symptoms screening recommendations. C-reactive protein (CRP) is a non-specific inflammatory biomarker that has been recently proposed for TB screening and can be quantitatively analyzed through cost-effective point-of-care assays. A previous meta-analysis found CRP high sensitive and moderate specific for active pulmonary TB with confirmed HIV infection. Methods: We performed an update meta-analysis of diagnostic tests, pooling sensitivities and specificities in order to assess the accuracy of CRP as a potential test for the screening of HIV-associated PTB in outpatients. We searched MEDLINE, Web of Science, and SCOPUS, for eligible articles before April 1st, 2020. Results: We identified 9 eligible studies with HIV-positive patients with PTB. At CRP threshold of 10mg/L, CRP pooled sensitivity was 86% and pooled specificity was 73%. Using CRP threshold of 8mg/L, pooled sensitivity was 81% and pooled specificity was 88%. We found that CRP has a high sensitivity in screening of PTB in HIV-positive outpatients, consistent with findings reported previously. Conclusions: Regardless of pooled specificity, better results were found using the CRP threshold of 8mg/L as a test screening of PTB, meeting the need of evaluation of antituberculosis treatment outcomes and reducing resource consumption.

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“…HDT can be used to improve long-term functional outcomes of respiratory tract infections (RTIs), such as MDR-Tb [32]. For example, in a Tb infection, Mtb down-regulates the expression of LL-37 in human macrophages; this reduction can be counteracted by treating the infected macrophages with vitD3, phenylbutyrate (PBA), or their combination [33]. Indeed, 1,25(OH) 2 -vitamin D modulates cathelicidin and defensin gene expression in innate immune cells, such as monocytes and macrophages [34].…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

Natale

Benedictis

et al. 2020

Antibiotics

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In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit different mechanisms of action (MOA), including the modification of DNA/RNA, protein and cell wall synthesis, permeabilization and modulation of gradients of cellular membranes. Nowadays, the large increase in antibiotic resistance represents a crucial problem to limit progression at the pandemic level of the diseases that seemed nearly eradicated, such as tuberculosis (Tb). Mycobacterium tuberculosis (Mtb) is intrinsically resistant to many antibiotics due to chromosomal mutations which can lead to the onset of novel strains. Consequently, the maximum pharmaceutical effort should be focused on the development of new therapeutic agents and antimicrobial peptides can represent a valuable option as a copious source of potential bioactive compounds. The introduction of a metal center can improve chemical diversity and hence specificity and bioavailability while, in turn, the coordination to peptides of metal complexes can protect them and enhance their poor water solubility and air stability: the optimization of these parameters is strictly required for drug prioritization and to obtain potent inhibitors of Mtb infections with novel MOAs. Here, we present a panoramic review of the most recent findings in the field of metal complex-peptide conjugates and their delivery systems with the potential pharmaceutical application as novel antibiotics in Mtb infections.

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Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation

Cited by 30 publications

References 154 publications

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

Screening Performance of C-Reactive Protein for Active Pulmonary Tuberculosis in HIV-Positive Patients: A Meta-analysis

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

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