Drug repurposing for the treatment of staphylococcal infections

Current Pharmaceutical Design

Volumn 21, Issue 16, 2015, Pages 2089-2100

  Thangamani, Shankar ^a   Mohammad, Haroon ^a   Younis, Waleed ^a   Seleem, Mohamed N ^a  

^a PURDUE UNIVERSITY   (United States)

Author keywords

Bacterial resistance; Immunomodulatory agents; MRSA; Multidrug resistance; Non antibiotics; Repurposing; Staphylococci; Virulence factors

Indexed keywords

AMPHOTERICIN B; ANTIBIOTIC AGENT; ATOVAQUONE; AURANOFIN; CHLOROQUINE; DACTINOMYCIN; DAPSONE; DAUNORUBICIN; DICYCLOVERINE; DISULFIRAM; DOXORUBICIN; DOXYCYCLINE; EBSELEN; EFLORNITHINE; EMEDASTINE; FLOXURIDINE; FLUOROURACIL; IMMUNOMODULATING AGENT; LEVOCABASTINE; MILTEFOSINE; MITHRAMYCIN; MITOMYCIN; OXYMETAZOLINE; PAROMOMYCIN; PROCHLORPERAZINE; PYRIMETHAMINE; SIMVASTATIN; SPIRAMYCIN; TRIFLUPROMAZINE; UNINDEXED DRUG; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTIRHEUMATIC AGENT; IMMUNOLOGIC FACTOR;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIAL INFECTION; BACTERIAL STRAIN; BACTERICIDAL ACTIVITY; BIOFILM; CLINICAL TRIAL (TOPIC); DRUG DESIGN; DRUG EFFICACY; DRUG REPOSITIONING; FOOD AND DRUG ADMINISTRATION; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE RESPONSE; IN VITRO STUDY; IN VIVO STUDY; MINIMUM INHIBITORY CONCENTRATION; MOLECULE; MULTIDRUG RESISTANCE; PATHOGENESIS; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; ANIMAL; DRUG EFFECTS; PROCEDURES; STAPHYLOCOCCAL INFECTIONS; TREATMENT OUTCOME; TRENDS;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTIFUNGAL AGENTS; ANTIRHEUMATIC AGENTS; DRUG REPOSITIONING; HUMANS; IMMUNOLOGIC FACTORS; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; TREATMENT OUTCOME;

EID: 84929460506     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612821666150310104416     Document Type: Article

References (184)

1. CDC. Antibiotic resistance threats in the United States, 2013. In: Centers for Disease Control and Prevention, editor 2013. p. 1-114.
2. ECDC. The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. In: European Centre for Disease Control and Prevention, editor. Stockholm 2009. p. 1-54.
3. ECDC. Annual Epidemiological Report 2013. Reporting on 2011 surveillance data and 2012 epidemic intelligence data. In: European Centre for Disease Control and Prevention, editor. Stockholm 2013; p. 1-260.
4. Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis 2001; 1(3): 147-55.
5. Layer F, Cuny C, Strommenger B, Witte W. Linezolid resistance in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. Int J Med Microbiol 2012; 302: 102.
6. Li X, Li HT, Li SQ, et al. Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B. Carcinogenesis 2012; 33(12): 2548-57.
7. Chong CR, Sullivan DJ. New uses for old drugs. Nature 2007; 448(7154): 645-6.
8. Cohen FJ. Macro trends in pharmaceutical innovation. Nat Rev Drug Discov 2005; 4(1): 78-84.
9. Jin G, Wong ST. Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov Today 2014; 19(5): 637-44.
10. DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Economics 2003; 22(2): 151-85.
11. Petsko GA. When failure should be the option. Bmc Biol 2010; 8.
12. Bernhard GC. Auranofin Therapy in Rheumatoid-Arthritis. J Lab Clin Med 1982; 100(2): 167-77.
13. Furst DE, Abruzzo JL, Katz WA, Dahl SL, Ward JR. Mechanism of Action, Pharmacology, Clinical Efficacy and Side-Effects of Auranofin - an Orally-Administered Organic Gold Compound for the Treatment of Rheumatoid-Arthritis. Pharmacotherapy 1983; 3(5): 284-98.
14. Shaw CF. Gold-based therapeutic agents. Chem Rev 1999; 99(9): 2589-600.
15. Berners-Price SJ, Filipovska A. Gold compounds as therapeutic agents for human diseases. Metallomics 2011; 3(9): 863-73.
16. Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, et al. A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med 2012; 18(6): 956-60.
17. Gottlieb NL. Pharmacology of Auranofin - Overview and Update. Scand J Rheumatol 1986: 19-28.
18. Cassetta MI, Marzo T, Fallani S, Novelli A, Messori L. Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections. Biometals : an Int J Role Metal Ions Biology, Biochem, Med 2014; 27(4): 787-91.
19. Hokai Y, Jurkowicz B, Fernandez-Gallardo J, et al. Auranofin and related heterometallic gold(I)-thiolates as potent inhibitors of methicillin- resistant Staphylococcus aureus bacterial strains. J Inorganic Biochem 2014; 138: 81-8.
20. Schewe T. Molecular actions of ebselen--an antiinflammatory antioxidant. General Pharmacol 1995; 26(6): 1153-69.
21. Azad GK, Tomar RS. Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways. Mol Biol Reports 2014; 41(8): 4865-79.
22. Muller A, Cadenas E, Graf P, Sies H. A novel biologically active seleno-organic compound--I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ 51 (Ebselen). Biochemical Pharmacol 1984; 33(20): 3235-9.
23. Maiorino M, Roveri A, Ursini F. Antioxidant effect of Ebselen (PZ 51): peroxidase mimetic activity on phospholipid and cholesterol hydroperoxides vs free radical scavenger activity. Arch Biochem Biophys 1992; 295(2): 404-9.
24. Handa Y, Kaneko M, Takeuchi H, Tsuchida A, Kobayashi H, Kubota T. Effect of an antioxidant, ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. Surgical Neurol 2000; 53(4): 323-9.
25. Kobayashi T, Ohta Y, Yoshino J. Preventive effect of ebselen on acute gastric mucosal lesion development in rats treated with compound 48/80. Eur J Pharmacol 2001; 414(2-3): 271-9.
26. Parnham MJ, Sies H. The early research and development of ebselen. Biochemical Pharmacol 2013; 86(9): 1248-53.
27. Singh N, Halliday AC, Thomas JM, et al. A safe lithium mimetic for bipolar disorder. Nature Communications 2013; 4: 1332.
28. Nozawa R, Yokota T, Fujimoto T. Susceptibility of methicillinresistant Staphylococcus aureus to the selenium-containing compound 2-phenyl-1, 2-benzoisoselenazol-3(2H)-one (PZ51). Antimicrobial Agents Chemotherapy 1989; 33(8): 1388-90.
29. Lu J, Vlamis-Gardikas A, Kandasamy K, et al. Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2013; 27(4): 1394-403.
30. Chan G, Hardej D, Santoro M, Lau-Cam C, Billack B. Evaluation of the antimicrobial activity of ebselen: role of the yeast plasma membrane H+-ATPase. J Biochem Mol Toxicol 2007; 21(5): 252-64.
31. Imai H, Masayasu H, Dewar D, Graham DI, Macrae IM. Ebselen protects both gray and white matter in a rodent model of focal cerebral ischemia. Stroke; a journal of cerebral circulation 2001; 32(9): 2149-54.
32. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013; 13(10): 714-26.
33. Hamilton-Miller JM. Antimicrobial activity of 21 anti-neoplastic agents. Br J Cancer 1984; 49(3): 367-9.
34. Barberi-Heyob M, Weber B, Merlin JL, et al. Evaluation of plasma 5-fluorouracil nucleoside levels in patients with metastatic breast cancer: relationships with toxicities. Cancer Chemotherapy Pharmacol 1995; 37(1-2): 110-6.
35. Sandrini MP, Shannon O, Clausen AR, Bjorck L, Piskur J. Deoxyribonucleoside kinases activate nucleoside antibiotics in severely pathogenic bacteria. Antimicrobial Agents Chemotherapy 2007; 51(8): 2726-32.
36. Roobol C, De Dobbeleer GB, Bernheim JL. 5-fluorouracil and 5- fluoro-2'-deoxyuridine follow different metabolic pathways in the induction of cell lethality in L1210 leukaemia. Br J Cancer 1984; 49(6): 739-44.
37. Daum RS. Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Eng J Med 2007; 357(4): 380-90.
38. DeLeo FR, Otto M, Kreiswirth BN, Chambers HF. Communityassociated meticillin-resistant Staphylococcus aureus. Lancet 2010; 375(9725): 1557-68.
39. Adler A, Temper V, Block CS, Abramson N, Moses AE. Panton- Valentine leukocidin-producing Staphylococcus aureus. Emerging Infectious Diseases 2006; 12(11): 1789-90.
40. Miller LG, Diep BA. Clinical practice: colonization, fomites, and virulence: rethinking the pathogenesis of community-associated methicillin-resistant Staphylococcus aureus infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008; 46(5): 752-60.
41. Gallelli L, Galasso O, Falcone D, et al. The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial. Osteoarthritis and cartilage / OARS, Osteoarthritis Res Soc 2013; 21(9): 1400-8.
42. Yan J, Sun J, Huang L, Fu Q, Du G. Simvastatin prevents neuroinflammation by inhibiting N-methyl-D-aspartic acid receptor 1 in 6- hydroxydopamine-treated PC12 cells. J Neurosci Res 2014; 92(5): 634-40.
43. Jialal I, Miguelino E, Griffen SC, Devaraj S. Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes. J Clin Endocrinol Metabol 2007; 92(8): 3136-40.
44. Wallace HJ, Stacey MC. Levels of tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors in chronic venous leg ulcers-- correlations to healing status. J Investigative Dermatol 1998; 110(3): 292-6.
45. Cowin AJ, Hatzirodos N, Rigden J, Fitridge R, Belford DA. Etanercept decreases tumor necrosis factor-alpha activity in chronic wound fluid. Wound repair and regeneration : official publication of the Wound Healing Society and. the European Tissue Repair Society 2006; 14(4): 421-6.
46. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discovery 2014; 13(6): 465-76.
47. Khanna S, Biswas S, Shang Y, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PloS one 2010; 5(3): e9539.
48. Fournier B, Philpott DJ. Recognition of Staphylococcus aureus by the innate immune system. Clin Microbiol Rev 2005; 18(3): 521-40.
49. Bitto A, Minutoli L, Altavilla D, et al. Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes. Pharmacological research : the official journal of the Italian Pharmacological Society 2008; 57(2): 159-69.
50. Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science 2009; 325(5944): 1089-93.
51. Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 2008; 6(1): 17-27.
52. Lebeis SL, Kalman D. Aligning antimicrobial drug discovery with complex and redundant host-pathogen interactions. Cell Host Microbe 2009; 5(2): 114-22.
53. Khodaverdian V, Pesho M, Truitt B, et al. Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus. Antimicrobial Agents Chemotherapy 2013; 57(8): 3645-52.
54. Weinandy F, Lorenz-Baath K, Korotkov VS, et al. A beta-lactonebased antivirulence drug ameliorates Staphylococcus aureus skin infections in mice. Chem Med Chem 2014; 9(4): 710-3.
55. Hilchie AL, Wuerth K, Hancock RE. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat Chem Biol 2013; 9(12): 761-8.
56. Ejim L, Farha MA, Falconer SB, et al. Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy. Nat Chem Biol 2011; 7(6): 348-50.
57. Kupferwasser LI, Yeaman MR, Nast CC, et al. Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureus. J Clin Investigation 2003; 112(2): 222-33.
58. Needs CJ, Brooks PM. Clinical pharmacokinetics of the salicylates. Clin Pharmacokinetics 1985; 10(2): 164-77.
59. Costa SS, Viveiros M, Amaral L, Couto I. Multidrug Efflux Pumps in Staphylococcus aureus: an Update. Open Microbiol J 2013; 7: 59-71.
60. Poole K. Efflux pumps as antimicrobial resistance mechanisms. Annl Med 2007; 39(3): 162-76.
61. Davis JM, Casper R. Antipsychotic drugs: clinical pharmacology and therapeutic use. Drugs 1977; 14(4): 260-82.
62. Lader M. Clinical pharmacology of antipsychotic drugs. J Int Med Res 1989; 17(1): 1-16.
63. Kaatz GW, Moudgal VV, Seo SM, Kristiansen JE. Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus. Antimicrobial Agents Chemotherapy 2003; 47(2): 719-26.
64. Kristiansen MM, Leandro C, Ordway D, et al. Thioridazine reduces resistance of methicillin-resistant staphylococcus aureus by inhibiting a reserpine-sensitive efflux pump. In vivo 2006; 20(3): 361-6.
65. Costa SS, Falcao C, Viveiros M, et al. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus. BMC Microbiology 2011; 11: 241.
66. McGoon MD, Vlietstra RE, Holmes DR, Jr., Osborn JE. The clinical use of verapamil. Mayo Clin Proceedings 1982; 57(8): 495-510.
67. Aeschlimann JR, Dresser LD, Kaatz GW, Rybak MJ. Effects of NorA inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciprofloxacin, and norfloxacin in genetically related strains of Staphylococcus aureus. Antimicrobial Agents Chemotherapy 1999; 43(2): 335-40.
68. Vetrivel U, Subramanian G, Dorairaj S. A novel in silico approach to identify potential therapeutic targets in human bacterial pathogens. The HUGO Journal 2011; 5(1-4): 25-34.
69. Amineni U, Pradhan D, Marisetty H. In silico identification of common putative drug targets in Leptospira interrogans. J Chemical Biol 2010; 3(4): 165-73.
70. Foster TJ. Immune evasion by staphylococci. Nat Rev Microbiol 2005; 3(12): 948-58.
71. Veldkamp KE, van Strijp JA. Innate immune evasion by staphylococci. Adv Exp Med Biol 2009; 666: 19-31.
72. Hornef MW, Wick MJ, Rhen M, Normark S. Bacterial strategies for overcoming host innate and adaptive immune responses. Nat Immunol 2002; 3(11): 1033-40.
73. McCormick JK, Yarwood JM, Schlievert PM. Toxic shock syndrome and bacterial superantigens: an update. Annl Rev Microbiol 2001; 55: 77-104.
74. Fraser JD. Clarifying the mechanism of superantigen toxicity. PLoS Biology 2011; 9(9): e1001145.
75. Cavaillon JM, Adib-Conquy M, Fitting C, Adrie C, Payen D. Cytokine cascade in sepsis. Scandinavian J Infectious Diseases 2003; 35(9): 535-44.
76. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev 2012; 25(2): 362-86.
77. Kwiecinski J, Rhost S, Lofbom L, et al. Sulfatide attenuates experimental Staphylococcus aureus sepsis through a CD1ddependent pathway. Infection Immunity 2013; 81(4): 1114-20.
78. Krakauer T. Update on staphylococcal superantigen-induced signaling pathways and therapeutic interventions. Toxins 2013; 5(9): 1629-54.
79. Watson AR, Janik DK, Lee WT. Superantigen-induced CD4 memory T cell anergy. I. Staphylococcal enterotoxin B induces Fynmediated negative signaling. Cellular Immunol 2012; 276(1-2): 16-25.
80. Bowdish DM, Davidson DJ, Scott MG, Hancock RE. Immunomodulatory activities of small host defense peptides. Antimicrobial Agents Chemotherapy 2005; 49(5): 1727-32.
81. Scott MG, Dullaghan E, Mookherjee N, et al. An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol 2007; 25(4): 465-72.
82. van der Does AM, Hensbergen PJ, Bogaards SJ, Cansoy M, Deelder AM, van Leeuwen HC, et al. The human lactoferrinderived peptide hLF1-11 exerts immunomodulatory effects by specific inhibition of myeloperoxidase activity. J Immunol 2012; 188(10): 5012-9.
83. Cirioni O, Silvestri C, Pierpaoli E, et al. IB-367 pre-treatment improves the in vivo efficacy of teicoplanin and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus. J Med Microbiol 2013; 62(Pt 10): 1552-8.
84. Silva RR, Shrestha-Bajracharya D, Almeida-Leite CM, Leite R, Bahia MT, Talvani A. Short-term therapy with simvastatin reduces inflammatory mediators and heart inflammation during the acute phase of experimental Chagas disease. Mem Inst Oswaldo Cruz 2012; 107(4): 513-21.
85. Al-Siyabi K, Farhan H, Al-Rasadi K, Al-Salhi A, Al-Hinai AT, Al- Zakwani I. Safety of simvastatin and goal attainment for lowdensity lipoprotein cholesterol in sultan qaboos university hospital. Oman Med J 2010; 25(4): 264-8.
86. Zago AC, Matte BS, Reginato L, et al. First-in-man study of simvastatin- eluting stent in de novo coronary lesions: the SIMVASTENT study. Circ J 2012; 76(5): 1109-14.
87. Gazzerro P, Proto MC, Gangemi G, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacological Rev 2012; 64(1): 102-46.
88. Bergman P, Linde C, Pütsep K, et al. Studies on the antibacterial effects of statins--in vitro and in vivo. PLoS One 2011; 6(8): e24394.
89. Masadeh M, Mhaidat N, Alzoubi K, Al-Azzam S, Alnasser Z. Antibacterial activity of statins: a comparative study of atorvastatin, simvastatin, and rosuvastatin. Ann Clin Microbiol Antimicrob 2012; 11: 13.
90. Farmer AR, Murray CK, Mende K, et al. Effect of HMG-CoA reductase inhibitors on antimicrobial susceptibilities for gramnegative rods. J Basic Microbiol 2013; 53(4): 336-9.
91. Cabral ME, Figueroa LI, Fariña JI. Synergistic antifungal activity of statin-azole associations as witnessed by Saccharomyces cerevisiaeand Candida utilis-bioassays and ergosterol quantification. Rev Iberoam Micol 2013; 30(1): 31-8.
92. Nalin DR. Comment on: unexpected antimicrobial effect of statins. J Antimicrob Chemother 2008; 61(6): 1400.
93. Menezes EA, Vasconcelos Júnior AA, Silva CL, Plutarco FX, Cunha MaC, Cunha FA. In vitro synergism of simvastatin and fluconazole against Candida species. Rev Inst Med Trop Sao Paulo 2012; 54(4): 197-9.
94. den Hollander WJ, Kuipers EJ. Commentary: simvastatin as the key to improving H. pylori eradication rates? Aliment Pharmacol Ther 2012; 36(5): 493; author reply 4.
95. Wu BQ, Luo JM, Wang YH, et al. Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages. Clin Exp Med 2013.
96. Sun HY, Singh N. Antimicrobial and immunomodulatory attributes of statins: relevance in solid-organ transplant recipients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2009; 48(6): 745-55.
97. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins and sepsis: multiple modifications at multiple levels. Lancet Infectious Dis 2007; 7(5): 358-68.
98. Wang HR, Li JJ, Huang CX, Jiang H. Fluvastatin inhibits the expression of tumor necrosis factor-alpha and activation of nuclear factor-kappaB in human endothelial cells stimulated by C-reactive protein. Clinica chimica acta; international journal of clinical chemistry 2005; 353(1-2): 53-60.
99. Grip O, Janciauskiene S, Lindgren S. Atorvastatin activates PPARgamma and attenuates the inflammatory response in human monocytes. Inflammation research : official journal of the European Histamine Research Society et al. 2002; 51(2): 58-62.
100. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353(9157): 983-4.
101. Diomede L, Albani D, Sottocorno M, et al. In vivo antiinflammatory effect of statins is mediated by nonsterol mevalonate products. Arteriosclerosis, Thrombosis, Vascular Biol 2001; 21(8): 1327-32.
102. Chang LT, Sun CK, Chiang CH, Wu CJ, Chua S, Yip HK. Impact of simvastatin and losartan on antiinflammatory effect: in vitro study. J Cardiovascular Pharmacol 2007; 49(1): 20-6.
103. Kanda H, Hamasaki K, Kubo K, et al. Antiinflammatory effect of simvastatin in patients with rheumatoid arthritis. J Rheumatol 2002; 29(9): 2024-6.
104. Devran O, Karakurt Z, Adiguzel N, et al. C-reactive protein as a predictor of mortality in patients affected with severe sepsis in intensive care unit. Multidisciplinary Respiratory Med 2012; 7(1): 47.
105. Lobo SM, Lobo FR, Bota DP, et al. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003; 123(6): 2043-9.
106. Chan KY, Boucher ES, Gandhi PJ, Silva MA. HMG-CoA reductase inhibitors for lowering elevated levels of C-reactive protein. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2004; 61(16): 1676-81.
107. Arnaud C, Burger F, Steffens S, et al. Statins reduce interleukin-6- induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arteriosclerosis, Thrombosis, Vascular Biol 2005; 25(6): 1231-6.
108. Marz W, Winkler K, Nauck M, Bohm BO, Winkelmann BR. Effects of statins on C-reactive protein and interleukin-6 (the Ludwigshafen Risk and Cardiovascular Health study). Am J Cardiol 2003; 92(3): 305-8.
109. Pruefer D, Scalia R, Lefer AM. Simvastatin inhibits leukocyteendothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arteriosclerosis, Thrombosis, Vascular Biol 1999; 19(12): 2894-900.
110. Weber C, Erl W, Weber KS, Weber PC. HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. J Am College Cardiol 1997; 30(5): 1212-7.
111. Yoshida M, Sawada T, Ishii H, et al. Hmg-CoA reductase inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro: involvement of Rho GTPase-dependent mechanism. Arteriosclerosis, Thrombosis, Vascular Biol 2001; 21(7): 1165-71.
112. Pruefer D, Makowski J, Schnell M, et al. Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin. Circulation 2002; 106(16): 2104-10.
113. Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2001; 33(8): 1352-7.
114. Kruger P, Fitzsimmons K, Cook D, Jones M, Nimmo G. Statin therapy is associated with fewer deaths in patients with bacteraemia. Intensive Care Med 2006; 32(1): 75-9.
115. Niren NM. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis 2006; 77(1 Suppl): 11-6.
116. Ungerstedt JS, Blomback M, Soderstrom T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol 2003; 131(1): 48-52.
117. Smith IM, Burmeister LF. Biochemically assisted antibiotic treatment of lethal murine Staphylococcus aureus septic shock. Am J Clin Nut 1977; 30(8): 1364-8.
118. Kyme P, Thoennissen NH, Tseng CW, et al. C/EBPepsilon mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J Clin Investigation 2012; 122(9): 3316-29.
119. Gombart AF, Krug U, O'Kelly J, An E, Vegesna V, Koeffler HP. Aberrant expression of neutrophil and macrophage-related genes in a murine model for human neutrophil-specific granule deficiency. J Leukocyte Biol 2005; 78(5): 1153-65.
120. Verbeek W, Lekstrom-Himes J, Park DJ, et al. Myeloid transcription factor C/EBPepsilon is involved in the positive regulation of lactoferrin gene expression in neutrophils. Blood 1999; 94(9): 3141-50.
121. Williams SC, Du Y, Schwartz RC, et al. C/EBPepsilon is a myeloid- specific activator of cytokine, chemokine, and macrophagecolony- stimulating factor receptor genes. J Biological Chem 1998; 273(22): 13493-501.
122. LeClaire RD, Kell W, Bavari S, Smith TJ, Hunt RE. Protective effects of niacinamide in staphylococcal enterotoxin-B-induced toxicity. Toxicology 1996; 107(1): 69-81.
123. Krakauer T, Buckley M. Dexamethasone attenuates staphylococcal enterotoxin B-induced hypothermic response and protects mice from superantigen-induced toxic shock. Antimicrobial Agents Chemotherapy 2006; 50(1): 391-5.
124. Krakauer T, Buckley MJ, Huzella LM, Alves DA. Critical timing, location and duration of glucocorticoid administration rescue mice from superantigen-induced shock and attenuate lung injury. Int Immunopharmacol 2009; 9(10): 1168-74.
125. Krakauer T. Differential inhibitory effects of interleukin-10, interleukin- 4, and dexamethasone on staphylococcal enterotoxininduced cytokine production and T cell activation. J Leukocyte Biol 1995; 57(3): 450-4.
126. Krakauer T, Buckley M. Efficacy of two FDA-approved drug combination in a mouse model of staphylococcal enterotoxin B-induced shock. Military Med 2013; 178(9): 1024-8.
127. Saunders RN, Metcalfe MS, Nicholson ML. Rapamycin in transplantation: a review of the evidence. Kidney Int 2001; 59(1): 3-16.
128. Krakauer T, Buckley M, Issaq HJ, Fox SD. Rapamycin protects mice from staphylococcal enterotoxin B-induced toxic shock and blocks cytokine release in vitro and in vivo. Antimicrobial Agents Chemotherapy 2010; 54(3): 1125-31.
129. Krakauer T, Buckley M. Intranasal rapamycin rescues mice from staphylococcal enterotoxin B-induced shock. Toxins 2012; 4(9): 718-28.
130. Krakauer T, Stiles BG. Pentoxifylline inhibits superantigen-induced toxic shock and cytokine release. Clin Diagnostic Laboratory Immunol 1999; 6(4): 594-8.
131. Huisinga JM, Pipinos, II, Stergiou N, Johanning JM. Treatment with pharmacological agents in peripheral arterial disease patients does not result in biomechanical gait changes. J App Biomechanics 2010; 26(3): 341-8.
132. Chung PY, Toh YS. Anti-biofilm agents: recent breakthrough against multi-drug resistant Staphylococcus aureus. Pathogens Disease 2014; 70(3): 231-9.
133. Chen M, Yu Q, Sun H. Novel strategies for the prevention and treatment of biofilm related infections. International J Mol Sci 2013; 14(9): 18488-501.
134. Dubreuil L, Houcke I, Mouton Y, Rossignol JF. In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrobial Agents Chemotherapy 1996; 40(10): 2266-70.
135. Tchouaffi-Nana F, Ballard TE, Cary CH, Macdonald TL, Sifri CD, Hoffman PS. Nitazoxanide inhibits biofilm formation by Staphylococcus epidermidis by blocking accumulation on surfaces. Antimicrobial Agents Chemotherapy 2010; 54(7): 2767-74.
136. Siles SA, Srinivasan A, Pierce CG, Lopez-Ribot JL, Ramasubramanian AK. High-throughput screening of a collection of known pharmacologically active small compounds for identification of Candida albicans biofilm inhibitors. Antimicrobial Agents Chemotherapy 2013; 57(8): 3681-7.
137. Shlaes DM, Sahm D, Opiela C, Spellbergc B. The FDA Reboot of Antibiotic Development. Antimicrobial Agents Chemotherapy 2013; 57(10): 4605-7.
138. FDA approves Sivextro to treat skin infections [press release]. June 20, 2014 2014.
139. FDA approves Dalvance to treat skin infections [press release]. May 23, 2014 2014.
140. Cooper MA, Shlaes D. Fix the antibiotics pipeline. Nature 2011; 472(7341): 32.
141. May M. Drug Development Time for Teamwork. Nature 2014; 509(7498): S4-S5.
142. Smorenburg CH, Seynaeve C, Bontenbal M, Planting AS, Sindermann H, Verweij J. Phase II study of miltefosine 6% solution as topical treatment of skin metastases in breast cancer patients. Anticancer Drugs 2000; 11(10): 825-8.
143. Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrobial Chemotherapy 2012; 67(11): 2576-97.
144. Meyerhoff A. U.S. Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1999; 28(1): 42-8; discussion 9-51.
145. Bukirwa H, Garner P, Critchley J. Chlorproguanil-dapsone for treating uncomplicated malaria. The Cochrane Database of Systematic Rev 2004(4): CD004387.
146. Olson KB, Thompson JF, Zintheo CJ. Treatment of pulmonary tuberculosis with diasone. Am Rev Tuberculosis 1945; 52: 474-82.
147. Robitzek EH, Ornstein GG, et al. Diasone in the treatment of pulmonary tuberculosis. Diseases Chest 1946; 12: 185-204.
148. Kannan G, Vasantha J, Rani NV, et al. Drug usage evaluation of dapsone. Indian J Pharml Sci 2009; 71(4): 456-60.
149. Abeloff MD, Rosen ST, Luk GD, Baylin SB, Zeltzman M, Sjoerdsma A. Phase II trials of alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, in advanced small cell lung cancer and colon cancer. Cancer Treatment Reports 1986; 70(7): 843-5.
150. Paulson YJ, Gilman TM, Heseltine PN, Sharma OP, Boylen CT. Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Chest 1992; 101(1): 67-74.
151. Burri C, Brun R. Eflornithine for the treatment of human African trypanosomiasis. Parasitol Res 2003; 90 Supp 1: S49-52.
152. Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA. Eflornithine is safer than melarsoprol for the treatment of secondstage Trypanosoma brucei gambiense human African trypanosomiasis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2005; 41(5): 748-51.
153. Robays J, Raguenaud ME, Josenando T, Boelaert M. Eflornithine is a cost-effective alternative to melarsoprol for the treatment of second- stage human West African trypanosomiasis in Caxito, Angola. Tropical medicine & international health : TM & IH 2008; 13(2): 265-71.
154. Tan KR, Magill AJ, Parise ME, Arguin PM, Centers for Disease C, Prevention. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Tropical Med Hygiene 2011; 84(4): 517-31.
155. Ben Salah A, Ben Messaoud N, Guedri E, et al. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Eng J Med 2013; 368(6): 524-32.
156. Monge-Maillo B, Lopez-Velez R. Topical paromomycin and gentamicin for new world cutaneous leishmaniasis in Panama. Am J Tropical Med Hygiene 2014; 90(6): 1191.
157. Sosa N, Capitan Z, Nieto J, et al. Randomized, double-blinded, phase 2 trial of WR 279, 396 (paromomycin and gentamicin) for cutaneous leishmaniasis in Panama. Am J Tropical Med Hygiene 2013; 89(3): 557-63.
158. Robert-Gangneux F, Darde ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 2012; 25(2): 264-96.
159. Baltzan M, Mehta S, Kirkham TH, Cosio MG. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respiratory Critical Care Med 1999; 160(1): 192-7.
160. Cohen HG, Reynolds TB. Comparison of metronidazole and chloroquine for the treatment of amoebic liver abscess. A controlled trial. Gastroenterology 1975; 69(1): 35-41.
161. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004; 363(9425): 1965-76.
162. Baggish AL, Hill DR. Antiparasitic agent atovaquone. Antimicrobial Agents Chemotherapy 2002; 46(5): 1163-73.
163. Araujo FG, Huskinson J, Remington JS. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrobial Agents Chemotherapy 1991; 35(2): 293-9.
164. Wilson T, Edeson JF. Treatment of acute malaria with pyrimethamine. Br Med J 1953; 1(4804): 253-5.
165. TOXOPLASMIC uveitis and pyrimethamine. Br Med J 1957; 2(5052): 1042-4.
166. Beuerman VA, Burnham CJ. Toxoplasmic uveitis; treatment with pyrimethamine and sulfadiazine. Am J Ophthalmol 1956; 42(2): 217-27.
167. Jacobs JY, Michel J, Sacks T. Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against Staphylococcus aureus. Antimicrobial Agents Chemotherapy 1979; 15(4): 580-6.
168. Phillips M, Malloy G, Nedunchezian D, Lukrec A, Howard RG. Disulfiram inhibits the in vitro growth of methicillin-resistant staphylococcus aureus. Antimicrobial Agents Chemotherapy 1991; 35(4): 785-7.
169. Dastidar SG, Debnath S, Mazumdar K, Ganguly K, Chakrabarty AN. Triflupromazine: a microbicide non-antibiotic compound. Acta microbiologica et immunologica Hungarica 2004; 51(1-2): 75-83.
170. Kruszewska H, Zareba T, Tyski S. Search of antimicrobial activity of selected non-antibiotic drugs. Acta Poloniae Pharmaceutica 2002; 59(6): 436-9.
171. Karak P, Kumar KA, Mazumdar K, Mookerjee M, Dastidar SG. Antibacterial potential of an antispasmodic drug dicyclomine hydrochloride. Ind J Med Res 2003; 118: 192-6.
172. Rani Basu L, Mazumdar K, Dutta NK, Karak P, Dastidar SG. Antibacterial property of the antipsychotic agent prochlorperazine, and its synergism with methdilazine. Microbiological Res 2005; 160(1): 95-100.
173. Jerwood S, Cohen J. Unexpected antimicrobial effect of statins. J Antimicrobial Chemotherapy 2008; 61(2): 362-4.
174. Chiu HC, Lee SL, Kapuriya N, et al. Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus. Bioorganic Med Chem 2012; 20(15): 4653-60.
175. Kruszewska H, Zareba T, Tyski S. Estimation of antimicrobial activity of selected non-antibiotic products. Acta Poloniae Pharmaceutica 2006; 63(5): 457-60.
176. Mandal A, Sinha C, Kumar Jena A, Ghosh S, Samanta A. An Investigation on in vitro and in vivo Antimicrobial Properties of the Antidepressant: Amitriptyline Hydrochloride. Brazilian journal of microbiology : publication of the Brazilian Society for Microbiology. 2010; 41(3): 635-45.
177. El-Nakeeb MA, Abou-Shleib HM, Khalil AM, Omar HG, El- Halfawy OM. In vitro antibacterial activity of some antihistaminics belonging to different groups against multi-drug resistant clinical isolates. Brazilian J microbiology : publication of the Brazilian Society for Microbiology. 2011; 42(3): 980-91.
178. Kruszewska H, Zareba T, Tyski S. Search of antimicrobial activity of selected non-antibiotic drugs. Acta Poloniae Pharmaceutica 2003/04/03 ed2002. p. 436-9.
179. Dutta NK, Annadurai S, Mazumdar K, et al. Potential management of resistant microbial infections with a novel non-antibiotic: the anti-inflammatory drug diclofenac sodium. Int J Antimicrobial Agents 2007; 30(3): 242-9.
180. Mazumdar K, Ganguly K, Kumar KA, Dutta NK, Chakrabarty AN, Dastidar SG. Antimicrobial potentiality of a new non-antibiotic: the cardiovascular drug oxyfedrine hydrochloride. Microbiological Res 2003; 158(3): 259-64.
181. Al-Janabi AA. In vitro antibacterial activity of Ibuprofen and acetaminophen. J Global Infectious Diseases 2010; 2(2): 105-8.
182. Kruszewska H, Zareba T, Tyski S. Examination of antimicrobial activity of selected non-antibiotic products. Acta Poloniae Pharmaceutica 2010; 67(6): 733-6.
183. Kruszewska H, Zareba T, Tyski S. Examination of antibacterial and antifungal activity of selected non-antibiotic products. Acta Poloniae Pharmaceutica 2008; 65(6): 779-82.
184. Munoz-Bellido JL, Munoz-Criado S, Garcia-Rodriguez JA. Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. Int J Antimicrobial Agents 2000; 14(3): 177-80.