Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort

Lai, Chih Cheng; Lee, Meng Tse Gabriel; Lee, Shih Hao; Hsu, Wan‐Ting; Chang, Shy Shin; Chen, Shyr‐Chyr; Lee, Chien‐Chang

doi:10.1136/thoraxjnl-2015-207052

Cited by 59 publications

(56 citation statements)

References 44 publications

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“…107 As adjunctive therapy in murine TB, statins shorten the time to culture negativity by 1 month, reduce tissue pathology, decrease the proportion of culturepositive relapse cases and enhance bacterial killing. [108][109] Statin usage by newly diagnosed type-2 diabetics did however, not prevent development of TB, 110 and further studies are required.…”

Section: Cholesterol-lowering Drugsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

313

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Cholesterol-lowering Drugsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

313

275

View full text Add to dashboard Cite

show abstract

“…Treatment with simvastatin in combination with canonical drugs, such as isoniazid, rifampin and pyrazinamide, shortens therapy duration in murine TB 55 . Moreover, a retrospective investigation in a large patient cohort that comprised more than 8,000 new TB cases and 800,000 control patients revealed that there is no risk of TB reactivation upon statin intake 56 . This study was prompted by epidemiological observations that statins improve the clinical outcome of respiratory infections.…”

Section: Tb Chemotherapymentioning

confidence: 99%

Host-directed therapies for bacterial and viral infections

Kaufmann

Dorhoi

Hotchkiss

et al. 2017

Nat Rev Drug Discov

568

440

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Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic.

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“…We have clearly demonstrated that OPN synthesis is effectively inhibited in vitro at less than 1 Statins, which suppress OPN production [27], and their use has been associated with a reduced risk of developing active TB in some studies [28]. Application of the newly-generated compounds to host-directed therapy may be possible.…”

Section: Discussionmentioning

confidence: 88%

Inhibition of Osteopontin Synthesis in THP-1 Cells Stimulated with Phorbol 12-Myristate 13-Acetate by Brefelamide Derivatives

Bai¹,

Matsuba²,

Kikuchi³

et al. 2019

Preprint

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Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

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Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort

Abstract: We found that statin therapy was associated with a decreased risk of active TB, and the length of statin therapy affected the TB protection. Given the observational nature of this study, the protective effect against active TB must be confirmed in future randomised trials.

Cited by 59 publications

References 44 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Host-directed therapies for bacterial and viral infections

Inhibition of Osteopontin Synthesis in THP-1 Cells Stimulated with Phorbol 12-Myristate 13-Acetate by Brefelamide Derivatives

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