The treatment of melioidosis: is there a role for repurposed drugs? A proposal and review

References

• Wuthiekanun V, Peacock SJ. Management of melioidosis. Expert Rev Anti Infect Ther. 2006 Jun;4(3):445–455.
   PubMedGoogle Scholar
• Maharjan B, Chantratita N, Vesaratchavest M, et al. Recurrent melioidosis in patients in northeast Thailand is frequently due to reinfection rather than relapse. J Clin Microbiol. 2005 Dec;43(12):6032–6034.
   PubMed Web of Science ®Google Scholar
• Limmathurotsakul D, Golding N, Dance DAB, et al. Predicted global distribution of burkholderia pseudomallei and burden of melioidosis [Letter]. Nat Microbiol. 2016 01 11;1:15008. online.
   Web of Science ®Google Scholar
• Limmathurotsakul D, Peacock SJ. Melioidosis: a clinical overview. Br Med Bull. 2011;99:125–139.
   PubMed Web of Science ®Google Scholar
• Estes DM, Dow SW, Schweizer HP, et al. Present and future therapeutic strategies for melioidosis and glanders. Expert Rev Anti Infect Ther. 2010 Mar;8(3):325–338.
   PubMed Web of Science ®Google Scholar
• Churuangsuk C, Chusri S, Hortiwakul T, et al. Characteristics, clinical outcomes and factors influencing mortality of patients with melioidosis in southern Thailand: A 10-year retrospective study. Asian Pac J Trop Med. 2016 Mar;9(3):256–260.
   PubMed Web of Science ®Google Scholar
• Gilad J, Harary I, Dushnitsky T, et al. Burkholderia mallei and burkholderia pseudomallei as bioterrorism agents: national aspects of emergency preparedness. Isr Med Assoc Journal: IMAJ. 2007 Jul;9(7):499–503.
   PubMed Web of Science ®Google Scholar
• Schweizer HP. When it comes to drug discovery not all gram-negative bacterial biodefence pathogens are created equal: burkholderia pseudomallei is different. Microb Biotechnol. 2012 Sep;5(5):581–583.
   PubMed Web of Science ®Google Scholar
• Stone JK, DeShazer D, Brett PJ, et al. Melioidosis: molecular aspects of pathogenesis. Expert Rev Anti Infect Ther. 2014 Dec;12(12):1487–1499.
   PubMed Web of Science ®Google Scholar
• Hajj Hussein I, Chams N, Chams S, et al. Vaccines through centuries: major cornerstones of global health. Frontiers in Public Health. 2015;3:269.
   PubMed Web of Science ®Google Scholar
• Aminov R. History of antimicrobial drug discovery - major classes and health impact. Biochem Pharmacol. 2017 Jun;1(133):4–19.
   Google Scholar
• Dance D. Treatment and prophylaxis of melioidosis. Int J Antimicrob Agents. 2014 Apr;43(4):310–318.
   PubMed Web of Science ®Google Scholar
• Laxminarayan R, Matsoso P, Pant S, et al. Access to effective antimicrobials: a worldwide challenge. Lancet (London, England). 2016 Jan 9;387(10014):168–175.
   PubMed Web of Science ®Google Scholar
• Zipperer A, Konnerth MC, Laux C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature. 2016 Jul 28;535(7613):511–516.
   PubMed Web of Science ®Google Scholar
• Montes-Worboys A, Brown S, Regev D, et al. Targeted delivery of amikacin into granuloma. Am J Respir Crit Care Med. 2010 Dec 15;182(12):1546–1553.
   PubMed Web of Science ®Google Scholar
• Merchant Z, Buckton G, Taylor KM, et al. A new era of pulmonary delivery of nano-antimicrobial therapeutics to treat chronic pulmonary infections. Curr Pharm Des. 2016;22(17):2577–2598.
   PubMed Web of Science ®Google Scholar
• Silva EB, Dow SW. Development of burkholderia mallei and pseudomallei vaccines. Front Cell Infect Microbiol. 2013;3:10.
   PubMed Web of Science ®Google Scholar
• Titball RW, Burtnick MN, Bancroft GJ, et al. Burkholderia pseudomallei and burkholderia mallei vaccines: are we close to clinical trials? Vaccine. 2017 Oct 20;35(44):5981–5989.
   PubMed Web of Science ®Google Scholar
• Graham BS, Ambrosino DM. History of passive antibody administration for prevention and treatment of infectious diseases. Curr Opin HIV AIDS. 2015 May;10(3):129–134.
   PubMed Web of Science ®Google Scholar
• AuCoin DP, Reed DE, Marlenee NL, et al. Polysaccharide specific monoclonal antibodies provide passive protection against intranasal challenge with burkholderia pseudomallei. PloS One. 2012;7(4):e35386.
   PubMed Web of Science ®Google Scholar
• Zhang S, Feng SH, Li B, et al. In vitro and in vivo studies of monoclonal antibodies with prominent bactericidal activity against burkholderia pseudomallei and burkholderia mallei. Clinical Vaccine Immunology: CVI. 2011 May;18(5):825–834.
   PubMed Web of Science ®Google Scholar
• Jones SM, Ellis JF, Russell P, et al. Passive protection against burkholderia pseudomallei infection in mice by monoclonal antibodies against capsular polysaccharide, lipopolysaccharide or proteins. J Med Microbiol. 2002 Dec;51(12):1055–1062.
   PubMed Web of Science ®Google Scholar
• Czaplewski L, Bax R, Clokie M, et al. Alternatives to antibiotics-a pipeline portfolio review. Lancet Infect Dis. 2016 Feb;16(2):239–251.
   PubMed Web of Science ®Google Scholar
• Allwood EM, Devenish RJ, Prescott M, et al. Strategies for intracellular survival of burkholderia pseudomallei. Front Microbiol. 2011 08 22;2:170.
   PubMed Web of Science ®Google Scholar
• Willcocks SJ, Denman CC, Atkins HS, et al. Intracellular replication of the well-armed pathogen burkholderia pseudomallei. Curr Opin Microbiol. 2016 Jan;21(29):94–103.
   Google Scholar
• Miyagi K, Kawakami K, Saito A. Role of reactive nitrogen and oxygen intermediates in gamma interferon-stimulated murine macrophage bactericidal activity against burkholderia pseudomallei. Infect Immun. 1997 Oct;65(10):4108–4113.
   PubMed Web of Science ®Google Scholar
• Debing Y, Jochmans D, Neyts J. Intervention strategies for emerging viruses: use of antivirals. Curr Opin Virol. 2013 Apr;3(2):217–224.
   PubMed Web of Science ®Google Scholar
• Gu L, Zhou S, Zhu L, et al. Small-molecule inhibitors of the type iii secretion system. Molecules (Basel, Switzerland). 2015;20(9):17659–17674.
   PubMed Web of Science ®Google Scholar
• Reuter K, Steinbach A, Helms V. Interfering with bacterial quorum sensing. Perspect Medicin Chem. 2016;8:1–15.
   PubMed Web of Science ®Google Scholar
• Miesel L, Greene J, Black TA. Genetic strategies for antibacterial drug discovery. Nat Reviews Genet. 2003 Jun;4(6):442–456.
   PubMed Web of Science ®Google Scholar
• Kang W-T, Vellasamy KM, Chua E-G, et al. Functional characterizations of effector protein bipc, a type iii secretion system protein, in burkholderia pseudomallei pathogenesis. J Infect Dis. 2015 Mar 1;211(5):827–834.
   PubMed Web of Science ®Google Scholar
• Gutierrez MG, Pfeffer TL, Warawa JM. Type 3 secretion system cluster 3 is a critical virulence determinant for lung-specific melioidosis. PLoS Negl Trop Dis. 2015 Jan;9(1):e3441.
   PubMed Web of Science ®Google Scholar
• Cummings JE, Kingry LC, Rholl DA, et al. The Burkholderia pseudomallei enoyl-acyl carrier protein reductase FabI1 is essential for in vivo growth and is the target of a novel chemotherapeutic with efficacy. Antimicrob Agents Chemother. 2014;58(2):931–935.
   PubMed Web of Science ®Google Scholar
• Heath RJ, White SW, Rock CO. Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl Microbiol Biotechnol. 2002 May;58(6):695–703.
   PubMed Web of Science ®Google Scholar
• Easton A, Haque A, Chu K, et al. A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis. 2007 Jan 1;195(1):99–107.
   PubMed Web of Science ®Google Scholar
• Cheng AC, Limmathurotsakul D, Chierakul W, et al. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2007 Aug 1;45(3):308–314.
   PubMed Web of Science ®Google Scholar
• van der Windt GJ, Wiersinga WJ, Wieland CW, et al. Osteopontin impairs host defense during established gram-negative sepsis caused by Burkholderia pseudomallei (melioidosis). PLoS Negl Trop Dis. 2010 Aug 31;4:(8)
   Web of Science ®Google Scholar
• Devenish RJ, Lai SC. Autophagy and burkholderia. Immunol Cell Biol. 2015 Jan;93(1):18–24.
   PubMed Web of Science ®Google Scholar
• Doitsh G, Galloway NL, Geng X, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature. 2014 Jan 23;505(7484):509–514.
   PubMed Web of Science ®Google Scholar
• Breitbach K, Sun GW, Kohler J, et al. Caspase-1 mediates resistance in murine melioidosis. Infect Immun. 2009 Apr;77(4):1589–1595.
   PubMed Web of Science ®Google Scholar
• Sun GW, Lu J, Pervaiz S, et al. Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell Microbiol. 2005 Oct;7(10):1447–1458.
   PubMed Web of Science ®Google Scholar
• Ceballos-Olvera I, Sahoo M, Miller MA, et al. Inflammasome-dependent pyroptosis and IL-18 protect against Burkholderia pseudomallei lung infection while IL-1beta is deleterious. PLoS Pathog. 2011 Dec;7(12):e1002452.
   PubMed Web of Science ®Google Scholar
• West TE, Myers ND, Chantratita N, et al. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis. PLoS Negl Trop Dis. 2014 Sep;8(9):e3178.
   PubMed Web of Science ®Google Scholar
• Bast A, Krause K, Schmidt IH, et al. Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages. PLoS Pathog. 2014 Mar;10(3):e1003986.
   PubMed Web of Science ®Google Scholar
• Bartel A, Gohler A, Hopf V, et al. Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines. PloS One. 2017;12(7):e0180203.
   PubMed Web of Science ®Google Scholar
• Koh GC, Maude RR, Schreiber MF, et al. Glyburide is anti-inflammatory and associated with reduced mortality in melioidosis. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2011 Mar 15;52(6):717–725.
   PubMed Web of Science ®Google Scholar
• Lamkanfi M, Mueller JL, Vitari AC, et al. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J Cell Biol. 2009 Oct 5;187(1):61–70.
   PubMed Web of Science ®Google Scholar
• Koh GC, Weehuizen TA, Breitbach K, et al. Glyburide reduces bacterial dissemination in a mouse model of melioidosis. PLoS Negl Trop Dis. 2013;7(10):e2500.
   PubMed Web of Science ®Google Scholar
• Liu X, Foo G, Lim WP, et al. Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response. PLoS Negl Trop Dis. 2014 Apr;8(4):e2795.
   PubMed Web of Science ®Google Scholar
• Kewcharoenwong C, Rinchai D, Utispan K, et al. Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection. Sci Rep. 2013;3:3363.
   PubMed Web of Science ®Google Scholar
• Propst KL, Troyer RM, Kellihan LM, et al. Immunotherapy markedly increases the effectiveness of antimicrobial therapy for treatment of Burkholderia pseudomallei infection. Antimicrob Agents Chemother. 2010 May;54(5):1785–1792.
   PubMed Web of Science ®Google Scholar
• Marshall JC. Sepsis: rethinking the approach to clinical research. J Leukoc Biol. 2008 Mar;83(3):471–482.
   PubMed Web of Science ®Google Scholar
• Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014 Apr;20(4):195–203.
   PubMed Web of Science ®Google Scholar
• Pinheiro Da Silva F, Cesar Machado MC. Personalized medicine for sepsis. Am J Med Sci. 2015 Nov;350(5):409–413.
   PubMed Web of Science ®Google Scholar
• Kruszewska H, Zareba T, Tyski S. Search of antimicrobial activity of selected non-antibiotic drugs. Acta Pol Pharm. 2002 Nov-Dec;59(6):436–439.
   PubMedGoogle Scholar
• Younis W, Thangamani S, Seleem MN. Repurposing non-antimicrobial drugs and clinical molecules to treat bacterial infections. Curr Pharm Des. 2015;21(28):4106–4111.
   PubMed Web of Science ®Google Scholar
• Doyle SL, Ozaki E, Brennan K, et al. IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration. Sci Transl Med. [2014 Apr 2];6(230):230ra44.
   PubMed Web of Science ®Google Scholar
• Cooper CL, Davis HL, Morris ML, et al. CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study. J Clin Immunol. 2004 Nov;24(6):693–701.
   PubMed Web of Science ®Google Scholar
• Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. with a report of ten original cases. 1893. Clin Orthop Relat Res. 1991 Jan;(262):3–11.
   PubMed Web of Science ®Google Scholar
• Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev. 2009 Mar 28;61(3):195–204.
   PubMed Web of Science ®Google Scholar
• Freidag BL, Melton GB, Collins F, et al. CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. Tuberculosis. Infection and Immunity 2000 May;68(5):2948–2953.
   PubMed Web of Science ®Google Scholar
• Wongratanacheewin S, Kespichayawattana W, Intachote P, et al. Immunostimulatory CpG oligodeoxynucleotide confers protection in a murine model of infection with Burkholderia pseudomallei. Infect Immun. 2004 Aug;72(8):4494–4502.
   PubMed Web of Science ®Google Scholar
• Judy BM, Taylor K, Deeraksa A, et al. Prophylactic application of CpG oligonucleotides augments the early host response and confers protection in acute melioidosis. PloS One. 2012;7(3):e34176.
   PubMed Web of Science ®Google Scholar
• Black S. Safety and effectiveness of MF-59 adjuvanted influenza vaccines in children and adults. Vaccine. 2015 Jun 8;33(Suppl 2):B3–5.
   PubMedGoogle Scholar
• Duncan MC, Linington RG, Auerbuch V. Chemical inhibitors of the type three secretion system: disarming bacterial pathogens. Antimicrob Agents Chemother. 2012 Nov;56(11):5433–5441.
   PubMed Web of Science ®Google Scholar
• Warrener P, Varkey R, Bonnell JC, et al. A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models. Antimicrob Agents Chemother. 2014 Aug;58(8):4384–4391.
   PubMed Web of Science ®Google Scholar
• Kaur Manjal S, Kaur R, Bhatia R, et al. Synthetic and medicinal perspective of thiazolidinones: A review. Bioorg Chem. 2017;75:406–423.
   PubMed Web of Science ®Google Scholar
• Felise HB, Nguyen HV, Pfuetzner RA, et al. An inhibitor of gram-negative bacterial virulence protein secretion. Cell Host Microbe. 2008 Oct 16;4(4):325–336.
   PubMed Web of Science ®Google Scholar
• Shioda H. A double blind controlled trial of N-(3ʹ,4ʹ-dimethoxycinnamoyl) anthranilic acid on children with bronchial asthma. N-5ʹ Study Group in Children. Allergy. 1979 Aug;34(4):213–219.
   PubMed Web of Science ®Google Scholar
• Naik R, Nixon S, Lopes A, et al. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. International Journal of Gynecological Cancer: Official Journal of the International Gynecological Cancer Society. 2006 Mar-Apr;16(2):786–790.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Munday R. Dithiolethiones for cancer chemoprevention: where do we stand? Mol Cancer Ther. 2008;7(11):3470–3479.
   PubMed Web of Science ®Google Scholar
• Miller WH, Seefeld MA, Newlander KA, et al. Discovery of aminopyridine-based inhibitors of bacterial enoyl-acp reductase (FabI). J Med Chem. [2002 07 01];45(15):3246–3256.
   PubMed Web of Science ®Google Scholar
• Judge SI, Bever CT Jr. Potassium channel blockers in multiple sclerosis: neuronal Kv channels and effects of symptomatic treatment. Pharmacology & Therapeutics. 2006 Jul;111(1):224–259.
   PubMed Web of Science ®Google Scholar
• Davey MS, Tyrrell JM, Howe RA, et al. A promising target for treatment of multidrug-resistant bacterial infections. Antimicrob Agents Chemother. 2011;55(7):3635–3636. . PubMed PMID: PMC3122435
   PubMed Web of Science ®Google Scholar
• Wallis RS, Zumla A. Vitamin D as adjunctive host-directed therapy in tuberculosis: A systematic review. Open Forum Infectious Diseases. 2016 Sep;3(3):ofw151.
   PubMed Web of Science ®Google Scholar
• Wallis RS, Hafner R. Advancing host-directed therapy for tuberculosis. Nat Reviews Immunol. 2015 Apr;15(4):255–263.
   PubMed Web of Science ®Google Scholar
• Degner NR, Wang JY, Golub JE, et al. Metformin use reverses the increased mortality associated with diabetes mellitus during tuberculosis treatment. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2018 Jan 6;66(2):198–205.
   PubMed Web of Science ®Google Scholar
• Dutta NK, Bruiners N, Pinn ML, et al. Statin adjunctive therapy shortens the duration of TB treatment in mice. J Antimicrob Chemother. 2016 Jun;71(6):1570–1577.
   PubMed Web of Science ®Google Scholar
• Abate G, Ruminiski PG, Kumar M, et al. New verapamil analogs inhibit intracellular mycobacteria without affecting the functions of mycobacterium-specific t cells. Antimicrob Agents Chemother. 2015 Dec 7;60(3):1216–1225.
   PubMed Web of Science ®Google Scholar
• Adams KN, Szumowski JD, Verapamil RL. its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. J Infect Dis. 2014 Aug 1;210(3):456–466.
   PubMed Web of Science ®Google Scholar
• de Knegt GJ, van Der Meijden A, de Vogel CP, et al. Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis in combination with potentiator drugs verapamil, timcodar, colistin and SQ109. Int J Antimicrob Agents. 2017 Mar;49(3):302–307.
   PubMed Web of Science ®Google Scholar
• Demitto Fde O, Do Amaral RC, Maltempe FG, et al. In vitro activity of rifampicin and verapamil combination in multidrug-resistant Mycobacterium tuberculosis. PloS One. 2015;10(2):e0116545.
   PubMed Web of Science ®Google Scholar
• Gupta A, Pant G, Mitra K, et al. Inhalable particles containing rapamycin for induction of autophagy in macrophages infected with Mycobacterium tuberculosis. Mol Pharm. 2014 Apr 7;11(4):1201–1207.
   PubMed Web of Science ®Google Scholar
• Gupta S, Tyagi S, Almeida DV, et al. Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor. Am J Respir Crit Care Med. 2013 Sep 1;188(5):600–607.
   Google Scholar
• Gupta S, Tyagi S, Bishai WR. Verapamil increases the bactericidal activity of bedaquiline against Mycobacterium tuberculosis in a mouse model. Antimicrob Agents Chemother. 2015 Jan;59(1):673–676.
   PubMed Web of Science ®Google Scholar
• Schiebler M, Brown K, Hegyi K, et al. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Mol Med. 2015 Feb;7(2):127–139.
   PubMed Web of Science ®Google Scholar
• Juarez E, Carranza C, Sanchez G, et al. Loperamide restricts intracellular growth of mycobacterium tuberculosis in lung macrophages. Am J Respir Cell Mol Biol. 2016 Dec;55(6):837–847.
   PubMed Web of Science ®Google Scholar
• Parumasivam T, Chan JG, Pang A, et al. In vitro evaluation of inhalable verapamil-rifapentine particles for tuberculosis therapy. Mol Pharm. 2016 Mar 7;13(3):979–989.
   PubMedGoogle Scholar
• Asakrah S, Nieves W, Mahdi Z, et al. Post-exposure therapeutic efficacy of COX-2 inhibition against Burkholderia pseudomallei. PLoS neglected tropical diseases. 2013 May 9;7(5):e2212.. * Demonstrates the utility of targeting Cox-2 (a highly druggable target) for treatment of melioidosis; 2013.
   Google Scholar
• Hua KF, Chou JC, Ka SM, et al. Cyclooxygenase-2 regulates NLRP3 inflammasome-derived IL-1beta production. J Cell Physiol. 2015 Apr;230(4):863–874.
   PubMed Web of Science ®Google Scholar
• Ponte-Sucre A, Mendoza-Leon A, Moll H. Experimental leishmaniasis: synergistic effect of ion channel blockers and interferon-gamma on the clearance of Leishmania major by macrophages. Parasitol Res. 2001 Jan;87(1):27–31.
   PubMed Web of Science ®Google Scholar
• Padron-Nieves M, Diaz E, Machuca C, et al. Glibenclamide modulates glucantime activity and disposition in Leishmania major. Exp Parasitol. 2009 Apr;121(4):331–337.
   PubMed Web of Science ®Google Scholar
• Haslett PA, Hanekom WA, Muller G, et al. Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro. J Infect Dis. 2003 Mar 15;187(6):946–955.
   PubMed Web of Science ®Google Scholar
• Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood. 2001 Jul 1;98(1):210–216.
   PubMed Web of Science ®Google Scholar
• Bodera P, Stankiewicz W. Immunomodulatory properties of thalidomide analogs: pomalidomide and lenalidomide, experimental and therapeutic applications. Recent Pat Endocr Metab Immune Drug Discov. 2011 Sep;5(3):192–196.
   PubMedGoogle Scholar
• Simpson AJ, Smith MD, Weverling GJ, et al. Prognostic value of cytokine concentrations (tumor necrosis factor-alpha, interleukin-6, and interleukin-10) and clinical parameters in severe melioidosis. J Infect Dis. 2000 Feb;181(2):621–625.
   PubMed Web of Science ®Google Scholar
• Lertmemongkolchai G, Cai G, Hunter CA, et al. Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens. Journal of Immunology (Baltimore, Md: 1950). 2001 Jan 15;166(2):1097–1105.
   PubMed Web of Science ®Google Scholar
• Brunel AS, Reynes J, Tuaillon E, et al. Thalidomide for steroid-dependent immune reconstitution inflammatory syndromes during AIDS. AIDS (London, England). 2012 Oct 23;26(16):2110–2112.
   PubMed Web of Science ®Google Scholar
• Lim H, Kane L, Schwartz JB, et al. Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients. Clin Exp Immunol. 2012 Aug;169(2):182–189.
   PubMed Web of Science ®Google Scholar
• Fu LM, Fu-Liu CS. Thalidomide and tuberculosis. The international journal of tuberculosis and lung disease. The Official Journal of the International Union against Tuberculosis and Lung Disease. 2002 Jul;6(7):569–572.
   PubMed Web of Science ®Google Scholar
• Kumar V, Harjai K, Chhibber S. Thalidomide treatment modulates macrophage pro-inflammatory function and cytokine levels in Klebsiella pneumoniae B5055 induced pneumonia in BALB/c mice. Int Immunopharmacol. 2010 Jul;10(7):777–783.
   PubMed Web of Science ®Google Scholar
• Milazzo L, Biasin M, Gatti N, et al. Thalidomide in the treatment of chronic hepatitis C unresponsive to alfa-interferon and ribavirin. Am J Gastroenterol. 2006 Feb;101(2):399–402.
   PubMed Web of Science ®Google Scholar
• Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Research Part C, Embryo Today: Reviews. 2015 Jun;105(2):140–156.
   PubMedGoogle Scholar
• Gamage AM, Lee KO. Anti-cancer drug hmba acts as an adjuvant during intracellular bacterial infections by inducing type I IFN through STING. J Immunol. 2017 Oct 1;199(7):2491–2502.
   PubMed Web of Science ®Google Scholar
• Opal SM, Fisher CJ Jr., Dhainaut JF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. the interleukin-1 receptor antagonist sepsis investigator group. Crit Care Med. 1997 Jul;25(7):1115–1124.
   PubMed Web of Science ®Google Scholar
• Weehuizen TA, Lankelma JM, De Jong HK, et al. Therapeutic administration of a monoclonal anti-il-1beta antibody protects against experimental melioidosis. Shock (Augusta, Ga). 2016 Nov;46(5):566–574.
   PubMed Web of Science ®Google Scholar
• Jang CH, Choi JH, Byun MS, et al. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford, England). 2006 Jun;45(6):703–710.
   PubMed Web of Science ®Google Scholar
• Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015;12:51.
   PubMed Web of Science ®Google Scholar
• Chua J, Senft JL, Lockett SJ, et al. pH alkalinization by chloroquine suppresses pathogenic burkholderia type 6 secretion system 1 and multinucleated giant cells. Infect Immun. 2017 Jan;85(1):e00586–16.
   PubMed Web of Science ®Google Scholar
• Charoensup J, Sermswan RW, Paeyao A, et al. High HMGB1 level is associated with poor outcome of septicemic melioidosis. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases. 2014;28:111–116.
   PubMed Web of Science ®Google Scholar
• Laws TR, Clark GC, D’Elia RV. Immune profiling of the progression of a BALB/c mouse aerosol infection by Burkholderia pseudomallei and the therapeutic implications of targeting HMGB1. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases. 2015 Nov;40:1–8.
   PubMed Web of Science ®Google Scholar
• Busani S, Damiani E, Cavazzuti I, et al. Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness. Minerva Anestesiol. 2016 May;82(5):559–572.
   PubMed Web of Science ®Google Scholar
• Marti-Carvajal AJ, Sola I, Lathyris D, et al. Human recombinant activated protein C for severe sepsis. The Cochrane Database of Systematic Reviews. 2012;3:Cd004388.
   Google Scholar
• Sanfilippo F, Santonocito C, Morelli A, et al. Beta-blocker use in severe sepsis and septic shock: a systematic review. Curr Med Res Opin. 2015;31(10):1817–1825.
   PubMed Web of Science ®Google Scholar
• Chawla S, DeMuro JP. Current controversies in the support of sepsis. Curr Opin Crit Care. 2014 Dec;20(6):681–684.
   PubMed Web of Science ®Google Scholar
• Altshuler AE, Kistler EB, Schmid-Schonbein GW. Autodigestion: proteolytic degradation and multiple organ failure in shock. Shock (Augusta, Ga). 2016 May;45(5):483–489.
   PubMed Web of Science ®Google Scholar
• Cheng AC, West TE, Limmathurotsakul D, et al. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med. 2008 Aug 19;5(8):e175.
   PubMed Web of Science ®Google Scholar