TUBERCULOSIS: BETWEEN THE OLD AND THE NEW

Andreea Daniela MECA; Maria BOGDAN; A. CAMEN; M.V. BOLDEANU; Paraschiva POSTOLACHE; Liliana MITITELU-TARTAU

Andreea Daniela MECA University of Medicine and Pharmacy, Craiova, Romania
Maria BOGDAN University of Medicine and Pharmacy, Craiova, Romania
A. CAMEN University of Medicine and Pharmacy, Craiova, Romania
M.V. BOLDEANU University of Medicine and Pharmacy, Craiova, Romania
Paraschiva POSTOLACHE “Grigore T. Popa” University of Medicine and Pharmacy Iasi
Liliana MITITELU-TARTAU “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Abstract

Isoniazid, rifampicin, ethambutol and pyrazinamide are administered in combination for at least 6 months in pulmonary tuberculosis (TB) -one of the first causes of death worldwide- and represent the first-line antituberculotic drugs, with different mechanisms of action, efficacy and toxicity. The susceptibility of the mycobacterial subpopulations to chemotherapy can be affected in immunocompromised patients so a systemic infection, post-primary, latent or even multi-drug resistant is then activated. There is an urgent need to develop new drugs or to repurpose existing ones, that have not yet been tested for their antimycobacterial activity. Moreover, the only available antitubercular vaccine does not imply protection against adult lung active TB, the most prevalent form. Additionally, the only new antitubercular agents approved in the last years - bedaquiline and delamanid - have not provided satisfactory results in eradicating this ancient disease. Recent studies have shown surprising information regarding the use of statins in TB, indicating that they limit the mycobacterial growth by promoting autophagy and apoptosis in macrophages and by inhibiting the synthesis of cholesterol, the precursor of the virulence factors. Other new findings in TB management include the beneficial effects of vitamin D supplementation, with increased healing rates, high bacterial toxicity and the observed decrease of resistant strain selection, when using phenothiazines in co-administration with isoniazid.

Author Biographies

Andreea Daniela MECA, University of Medicine and Pharmacy, Craiova, Romania

Faculty of Pharmacy

Maria BOGDAN, University of Medicine and Pharmacy, Craiova, Romania

Faculty of Pharmacy

A. CAMEN, University of Medicine and Pharmacy, Craiova, Romania

Faculty of Dental Medicine

M.V. BOLDEANU, University of Medicine and Pharmacy, Craiova, Romania

Faculty of Medicine

Paraschiva POSTOLACHE, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Medicine

Liliana MITITELU-TARTAU, “Grigore T. Popa” University of Medicine and Pharmacy Iasi

Faculty of Medicine

References

1. Leylabadlo HE, Kafil HS, Yousedi M, et al. Pulmonary tuberculosis diagnosis: where are we ? TRD 2016; (79): 134-142.
2. Rang HP, Ritter JM, Flower RJ, et al. Rang and Dale’s Pharmacology, Elsevier Churchill Livingstone, 8th edition, 2016, Section 5, Drugs used for the treatment of infections and cancer, Section 51, Antibacterial drugs, 626-641.
3. Bullock S, Manias E, Fundamentals of Pharmacology, Pearson Australia, 7th edition, 2014, Section XIV, The modulation of cellular growth and proliferation, Chapter 73, Antituberculotic and Antileprotic Agents, 948-959.
4. Flores-Villalva S, Rodriguez-Hernandez E, Rubio-Venegas Y, et al. What can proteomics tell us about tuberculosis ? JMB 2015; 25(8): 1181-1194.
5. Banu EA, Scorpan C, Mihailov O, Manole A, Mihai M, Ciuhodaru M, Ciocan AM, Duceac LD, Epidemiological aspects of pediatric tuberculosis in eastern part of Romania. Rev Med Chir Soc Med Nat Iaşi 2017; 121(4): 763-769.
6. Grigorescu C, Floria M, Antohe I, Afrasanie V, Baroi GL, Scripcariu V, Tuberculosis pleuro-pericarditis: so much fibrin! Case report. Rev Med Chir Soc Med Nat Iaşi 2018; 122(2): 300-303.
7. Ionescu L, Danila R, Trifescu I, Mihai F, Andriescu C, Ambrosie L, Late cervical nodal tuberculosis recurrence mimicking metastasis of papillary thyroid carcinoma. A case report. Rev Med Chir Soc Med Nat Iaşi 2017; 121(2): 356-359.
8. Nitu FM, Olteanu M, Streba CT, et al. Tuberculosis and its particularities in Romania and worldwide, RJME 2017; 58(2): 385-392.
9. Popescu MR, Plesea IE, Olaru M, et al. Morphological aspects in tuberculosis of oral cavity our experience and a review of the literature attempt, RJME 2015; 56(3): 967-987.
10. Nemes RM, Ianosi ES, Pop CS, et al. Tuberculosis of the oral cavity. RJME 2015; 56(2): 521-525.
11. Jimborean G, Ianosi ES, Csipor A, Postolache P, Training the Future Trainers – Intensifying Anti-smoking Education for a Better Community Health. Revista de Chimie 2017; 68(9): 2129-2131.
12. Gibson SER, Harrison J, Cox JAG, Modelling a silent epidemic: a review of the in vitro models of latent tuberculosis, MDPI Journal, Pathogens 2018; 7: 88.
13. ***WHO, Global Tuberculosis Report, 2018.
14. Katzung GB, Masters BS, Trevor JA, Basic&Clinical Pharmacology, McGrawHill Medical, 2012, 12th edition, Section VIII, Chemotherapeutic Drugs, Chapter 47, Antimycobacterial drugs, 839-848.
15. Barberis I, Bragazzi NL, Galluzo L, et al. The history of tuberculosis: from the first historical records to the isolation of Koch’s bacillus. JPMH 2017; 58: 9-12.
16. DiPiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy A pathophysiologic Approach, United States of America: Mc Graw Hill Education, 10th edition, Chapter 112: Tuberculosis, 4941-4988.
17. Holmes KK, Bertozzi S, Bloom BR, Jha P. Major Infectious Diseases, Washington (DC) 2017, 3rd edition, Volume 6, Disease Control Priorities, Chapter 11, Tuberculosis, 233-313.
18. Lenaerts A, Barry III CE, Dartois V, Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses. Imunological Reviews 2015; 264: 288-307.
19. Dutta NK, Karakousis PC, Latent Tuberculosis Infection: Myths, models and molecular mechanisms, MMBR 2014; 78(3): 343-371.
20. Evangelopoulos D, Diniz da Fonseca J, Waddell SJ, Understanding anti-tuberculosis drug efficacy: rethinking bacterial populations and how we model them, Elsevier Int J Infect Dis 2015; (32): 76-80.
21. Xu G, Wang J, Gao GF, et al. Insights into battles between Mycobacterium tuberculosis and macro-phages, Protein Cell 2014; 5(10): 728-736.
22. Chakraborty S, Rhee KY, Tuberculosis drug development: history and evolution of the mechanism-based paradigm, Cold Spring Harb Perspect Med 2015; 5: a021147.
23. Ferraris DM, Miggiano R, Rossi F, et al. Mycobacterium tuberculosis-Molecular determinants of infection, survival strategies and vulnerable targets. MDPI Journal, Pathogens 2018; 7, 17.
24. Hunter RL, Actor JK, Hwang S et al., Pathogenesis and animal models of post-primary (bronchogenic) tuberculosis, A review, MDPI Journal, Pathogens 2018; 7: 19.
25. Verrall AJ, Netea MG, Alisjahbana B, et al. Early clearance of Mycobacterium tuberculosis: a new frontier in prevention, J Immunol 2013; 141: 506-513.
26. Winters N, Butler-Laporte G, Menzies D, Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment, Eur Respir J 2015; 46: 1461-1470.
27. Tobin DM, Host-directed therapies for tuberculosis, Cold Spring Harb Perspect Med 2015; 5: a021196.
28. Moodley R, Godec TR. Short-course treatment for multidrug-resistant tuberculosis: the STREAMS trials, Eur Respir Rev 2016; 25: 29-35.
29. Nunn AJ, Philips PPJ, Meredith SK, et al. A trial of a shorter regimen for rifampin-resistant tubercu-losis, N Engl J Med 2019; 380: 1201-1213.
30. Skerry C, Pinn ML, Bruiners N, et al. Simvastatin increases the in vivo activity of the first line tuber-culosis regimen, J Antimicrob Chemother 2014; 69: 2453-2457.
31. Lobato LS, Sammarco Rosa P, Silva Ferreira J. et al. Statins increase Rifampin mycobactericidal effect, Antimicrob Agents Chemother 2014; 58: 5766-5774.
32. Dutta NK, Bruiners N, Pinn ML et al., Statin adjunctive therapy shortens the duration of TB treatment, J Antimicrob Chemother 2016; 71: 1570-1577.
33. Guerra-De-Blas PC, Torres-Gonzales P, Bobadilla-Del-Valle M, et al. Potential effect of statins on Mycobacterium tuberculosis infection, Hindawi J Immunol Res 2018; 1-14.
34. Parihar SP, Guler R, Khutlang R, et al. Statin therapy reduces the Mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation, J Infect Dis 2014; 209: 754-763.
35. Rens C, Laval F, Daffe M, et al. Effects of Lipid-lowering drugs on vancomycin susceptibility of mycobacteria, , Antimicrob Agents Chemother 2016; (60): 10: 6193- 6199.
36. Yeh JJ, Lin CL, Hsu CY, et al. Statin for tuberculosis and pneumonia in patients with asthma-chronic pulmonary disease overlap syndrome: a time-dependent population-based cohort study, J Clin Med 2018; (7):381- 1-14.
37. Salie S, Hsu NJ, Semenya D, et al. Novel non-neuroleptic phenothiazines inhibit Mycobacterium tuberculosis replication, J Antimicrob Chemother 2014; 69: 1551-1558.
38. Kristiansen JE, Dastidar SG, Palchoudhuri S et al., Phenothiazines as a solution for multi drug resistant tuberculosis: From the origin to present, Int Microb, 2015; 18:1-12.
39. Dutta NK, Pinn ML, Karakousis PC. Reduced emergence of isoniazid resistance with concurrent use of thioridazine against acute murine tuberculosis, Antimicrob Agents Chemother 2014; 58: 4048-4053.
40. Angeby K, Jureen P, Chryssanthou E, et al. Tentative susceptibility testing breakpoint for the neuro-leptic drug thioridazine, a treatment option for multi- and extensively drug resistant tuberculosis, Elsevier Int J Mycobacter I 2012; 1(4): 177-179.
41. Dutta NK, Pinn ML, Karakousis PC, Sterilizing activity of thioridazine in combination with the first-drug regimen against acute murine tuberculosis, Antimicrob Agents Chemother 2014; 58(9): 5567-5569.