Skip to content
2000
Volume 32, Issue 4
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Due to the ever-increasing rate of antibacterial resistance, the search for effective antibacterial agents has become imperative. Researchers have investigated the potential antimicrobial properties of various classes of nonantibiotic drugs. Statins are a group of antihyperlipidemic drugs with several cholesterol-independent effects, including anti-inflammatory, immune-modulating, antioxidant, and antibacterial effects. and studies have demonstrated the antibacterial properties of statins against various gram-positive and gram-negative bacteria. Simvastatin and atorvastatin are the most potent members of the family. Their antibacterial effect can be attributed to several direct and indirect mechanisms. Bacterial invasion, growth, and virulence are affected by statins. However, since minimum inhibitory concentrations (MICs) are significantly higher than serum concentrations at the lipid-lowering dosage, indirect mechanisms have been suggested to explain the positive clinical results, including reducing inflammation and improving immune response capacity. Further, statins have shown promising results when combined with antibiotics and other antibacterial agents, such as triazenes and silver nanoparticles. Despite this, the controversial aspects of statins have cast doubt on their efficacy as a possible solution for antibacterial resistance, and further research is required. Consequently, this review will examine in detail the current clinical and findings and controversies regarding statins’ antibacterial properties and their relevance to antibacterial resistance.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0929867331666230829141301
2023-09-07
2025-04-18
Loading full text...

Full text loading...

References

  1. World Health OrganizationAntimicrobial resistance: Global report on surveillance.GenevaWorld Health Organization2014
    [Google Scholar]
  2. PulingamT. ParumasivamT. GazzaliA.M. SulaimanA.M. CheeJ.Y. LakshmananM. ChinC.F. SudeshK. Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome.Eur. J. Pharm. Sci.202217010610310.1016/j.ejps.2021.106103 34936936
    [Google Scholar]
  3. HanssonK. BrenthelA. Imagining a post-antibiotic era: A cultural analysis of crisis and antibiotic resistance.Med. Humanit.202248338138810.1136/medhum‑2022‑012409 35922118
    [Google Scholar]
  4. AbavisaniM. GoudarziM. GhalavandZ. HajikhaniB. RadZ.R. RadZ.R. HashemiA. Evaluation of efflux pumps overexpression and β-lactamase genes among colistin resistant Pseudomonas aeruginosa.Gene Rep.20212410130110.1016/j.genrep.2021.101301
    [Google Scholar]
  5. AbavisaniM. KhayamiR. HoseinzadehM. KodoriM. KesharwaniP. SahebkarA. CRISPR-Cas system as a promising player against bacterial infection and antibiotic resistance.Drug Resist. Updat.20236810094810.1016/j.drup.2023.100948 36780840
    [Google Scholar]
  6. LarssonD.G.J. FlachC.F. Antibiotic resistance in the environment.Nat. Rev. Microbiol.202220525726910.1038/s41579‑021‑00649‑x 34737424
    [Google Scholar]
  7. AnderssonD.I. HughesD. Microbiological effects of sublethal levels of antibiotics.Nat. Rev. Microbiol.201412746547810.1038/nrmicro3270 24861036
    [Google Scholar]
  8. AbavisaniM. BostanghadiriN. GhahramanpourH. KodoriM. AkramiF. FathizadehH. HashemiA. Rastegari-PouyaniM. Colistin resistance mechanisms in Gram-negative bacteria: A focus on Escherichia coli.Lett. Appl. Microbiol.2023762ovad02310.1093/lambio/ovad023 36754367
    [Google Scholar]
  9. AnderssonD.I. HughesD. Persistence of antibiotic resistance in bacterial populations.FEMS Microbiol. Rev.201135590191110.1111/j.1574‑6976.2011.00289.x 21707669
    [Google Scholar]
  10. AshburnT.T. ThorK.B. Drug repositioning: Identifying and developing new uses for existing drugs.Nat. Rev. Drug Discov.20043867368310.1038/nrd1468 15286734
    [Google Scholar]
  11. BlahaM.J. MartinS.S. How do statins work?: Changing paradigms with implications for statin allocation.J. Am. Coll. Cardiol.201362252392239410.1016/j.jacc.2013.08.1626 24067403
    [Google Scholar]
  12. MasadehM. MhaidatN. AlzoubiK. Al-azzamS. AlnasserZ. Antibacterial activity of statins: A comparative study of Atorvastatin, Simvastatin, and Rosuvastatin.Ann. Clin. Microbiol. Antimicrob.20121111310.1186/1476‑0711‑11‑13 22564676
    [Google Scholar]
  13. BergmanP. LindeC. PütsepK. PohankaA. NormarkS. Henriques-NormarkB. AnderssonJ. Björkhem-BergmanL. Studies on the antibacterial effects of statins-in vitro and in vivo.PLoS One201168e2439410.1371/journal.pone.0024394 21912631
    [Google Scholar]
  14. QiaoJ. KontoyiannisD.P. WanZ. LiR. LiuW. Antifungal activity of statins against Aspergillus species.Med. Mycol.200745758959310.1080/13693780701397673 18033614
    [Google Scholar]
  15. TavakkoliA. JohnstonT.P. SahebkarA. Antifungal effects of statins.Pharmacol. Ther.202020810748310.1016/j.pharmthera.2020.107483 31953128
    [Google Scholar]
  16. GoldsteinJ.L. BrownM.S. Regulation of the mevalonate pathway.Nature1990343625742543010.1038/343425a0 1967820
    [Google Scholar]
  17. KozarovE. PadroT. BadimonL. View of statins as antimicrobials in cardiovascular risk modification.Cardiovasc. Res.2014102336237410.1093/cvr/cvu058 24623278
    [Google Scholar]
  18. SahebkarA. KotaniK. SerbanC. UrsoniuS. MikhailidisD.P. JonesS.R. RayK.K. BlahaM.J. RyszJ. TothP.P. MuntnerP. LipG.Y. BanachM. Lipid and blood pressure meta-analysis collaboration (LBPMC) group. Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials.Atherosclerosis2015241243344210.1016/j.atherosclerosis.2015.05.022
    [Google Scholar]
  19. BlandA.R. PayneF.M. AshtonJ.C. JamialahmadiT. SahebkarA. The cardioprotective actions of statins in targeting mitochondrial dysfunction associated with myocardial ischaemia-reperfusion injury.Pharmacol. Res.202217510598610.1016/j.phrs.2021.105986 34800627
    [Google Scholar]
  20. FerrettiG. BacchettiT. SahebkarA. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials.Prog. Lipid Res.201560507310.1016/j.plipres.2015.08.003 26416579
    [Google Scholar]
  21. Vahedian-AzimiA. MohammadiS.M. BanachM. BeniF.H. GuestP.C. Al-RasadiK. JamialahmadiT. Sahebkar, A. Improved COVID-19 outcomes following statin therapy: An updated systematic review and meta-analysis.BioMed Res. Int.2021190177210.1155/2021/1901772
    [Google Scholar]
  22. ParizadehS.M.R. AzarpazhoohM.R. MoohebatiM. NematyM. Ghayour-MobarhanM. TavallaieS. RahseparA.A. AminiM. SahebkarA. MohammadiM. FernsG.A.A. Simvastatin therapy reduces prooxidant-antioxidant balance: Results of a placebo-controlled cross-over trial.Lipids201146433334010.1007/s11745‑010‑3517‑x 21207250
    [Google Scholar]
  23. SahebkarA. ChewG.T. WattsG.F. Recent advances in pharmacotherapy for hypertriglyceridemia.Prog. Lipid Res.2014561476610.1016/j.plipres.2014.07.002 25083925
    [Google Scholar]
  24. SerbanC. SahebkarA. UrsoniuS. MikhailidisD.P. RizzoM. LipG.Y. Kees HovinghG. KasteleinJ.J. KalinowskiL. RyszJ. BanachM. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations.Sci. Reports20155990210.1038/srep09902
    [Google Scholar]
  25. SohrevardiS. NasabF. MirjaliliM. BagherniyaM. TaftiA. JarrahzadehM. AzarpazhoohM. SaeidmaneshM. BanachM. JamialahmadiT. SahebkarA. Effect of atorvastatin on delirium status of patients in the intensive care unit: A randomized controlled trial.Arch. Med. Sci.20191751423142810.5114/aoms.2019.89330 34522273
    [Google Scholar]
  26. AminF. FathiF. ReinerŽ. BanachM. SahebkarA. The role of statins in lung cancer.Arch. Med. Sci.202118114115210.5114/aoms/123225 35154535 PMC8826694
    [Google Scholar]
  27. HariyantoT.I. KurniawanA. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection.Diabetes Metab. Syndr.20201461613161510.1016/j.dsx.2020.08.023 32882643
    [Google Scholar]
  28. Shrivastava-RanjanP. FlintM. Bergeron, É. McElroy, A.K.; Chatterjee, P.; Albariño, C.G.; Nichol, S.T.; Spiropoulou, C.F. Statins suppress Ebola virus infectivity by interfering with glycoprotein processing.MBio201893e006601810.1128/mBio.00660‑18 29717011
    [Google Scholar]
  29. Rojo-ArreolaL. LongT. AsarnowD. SuzukiB.M. SinghR. CaffreyC.R. Chemical and genetic validation of the statin drug target to treat the helminth disease, schistosomiasis.PLoS One201491e8759410.1371/journal.pone.0087594 24489942
    [Google Scholar]
  30. PariharS.P. GulerR. BrombacherF. Statins: A viable candidate for host-directed therapy against infectious diseases.Nat. Rev. Immunol.201919210411710.1038/s41577‑018‑0094‑3 30487528
    [Google Scholar]
  31. GrazianoT.S. CuzzullinM.C. FrancoG.C. Schwartz-FilhoH.O. de AndradeE.D. GroppoF.C. Cogo-MüllerK. Statins and antimicrobial effects: Simvastatin as a potential drug against Staphylococcus aureus biofilm.PLoS One2015105e012809810.1371/journal.pone.0128098 26020797
    [Google Scholar]
  32. CannonC.P. BraunwaldE. McCabeC.H. RaderD.J. RouleauJ.L. BelderR. JoyalS.V. HillK.A. PfefferM.A. SkeneA.M. Intensive versus moderate lipid lowering with statins after acute coronary syndromes.N. Engl. J. Med.2004350151495150410.1056/NEJMoa040583 15007110
    [Google Scholar]
  33. JerwoodS. CohenJ. Unexpected antimicrobial effect of statins.J. Antimicrob. Chemother.200761236236410.1093/jac/dkm496 18086693
    [Google Scholar]
  34. WelshA.M. KrugerP. FaoagaliJ. Antimicrobial action of atorvastatin and rosuvastatin.Pathology200941768969110.3109/00313020903305860 20001351
    [Google Scholar]
  35. WangC.C. YangP.W. YangS.F. HsiehK.P. TsengS.P. LinY.C. Topical simvastatin promotes healing of Staphylococcus aureus -contaminated cutaneous wounds.Int. Wound J.20161361150115710.1111/iwj.12431 25752328
    [Google Scholar]
  36. ThangamaniS. MohammadH. AbushahbaM.F.N. HamedM.I. SobreiraT.J.P. HedrickV.E. PaulL.N. SeleemM.N. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent.Sci. Rep.2015511640710.1038/srep16407 26553420
    [Google Scholar]
  37. WhitakerE. AlshammariA. Bacteriostatic effect of simvastatin on selected oral Streptococci in vitro.Contemp. Clin. Dent.201781596310.4103/ccd.ccd_848_16 28566853
    [Google Scholar]
  38. EmaniS. GunjiganurG. MehtaD. Determination of the antibacterial activity of simvastatin against periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: An in vitro study.Contemp. Clin. Dent.20145337738210.4103/0976‑237X.137959 25191077
    [Google Scholar]
  39. KamińskaM. AlikoA. HellvardA. BieleckaE. BinderV. MarczykA. PotempaJ. DelaleuN. KantykaT. MydelP. Effects of statins on multispecies oral biofilm identify simvastatin as a drug candidate targeting Porphyromonas gingivalis.J. Periodontol.201990663764610.1002/JPER.18‑0179 30506795
    [Google Scholar]
  40. TrombettaR.P. LowakK. AlbachA. LopezR. RomanoD. SanchezC. The in vitro evaluation of statins as antimicrobials for trauma-related chronic infection.Research Square202010.21203/rs.3.rs‑15891/v1
    [Google Scholar]
  41. ProctorR. Respiration and small colony variants of Staphylococcus aureus.J. Periodontol.20197310.1128/microbiolspec.GPP3‑0069‑2019
    [Google Scholar]
  42. SpoeringA.L. LewisK. Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials.J. Bacteriol.2001183236746675110.1128/JB.183.23.6746‑6751.2001 11698361
    [Google Scholar]
  43. MohammadS. NguyenH. NguyenM. Abdel-RasoulM. NguyenV. NguyenC.D. NguyenK.T. LiL. KitzmillerJ.P. Pleiotropic effects of statins: Untapped potential for statin pharmacotherapy.Curr. Vasc. Pharmacol.201917323926110.2174/1570161116666180723120608 30033872
    [Google Scholar]
  44. NovackV. EisingerM. FrenkelA. TerblancheM. AdhikariN.K.J. DouvdevaniA. AmichayD. AlmogY. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: A randomized double-blind placebo controlled clinical trial.Intensive Care Med.20093571255126010.1007/s00134‑009‑1429‑0 19205663
    [Google Scholar]
  45. FernandezR. De PedroV.J. ArtigasA. Statin therapy prior to ICU admission: Protection against infection or a severity marker?Intensive Care Med.200632116016410.1007/s00134‑005‑2743‑9 16086178
    [Google Scholar]
  46. NagendranM. McAuleyD.F. KrugerP.S. PapazianL. TruwitJ.D. LaffeyJ.G. ThompsonB.T. ClarkeM. GordonA.C. Statin therapy for acute respiratory distress syndrome: An individual patient data meta-analysis of randomised clinical trials.Intensive Care Med.201743566367110.1007/s00134‑016‑4649‑0 28004129
    [Google Scholar]
  47. PapazianL. RochA. CharlesP-E. Penot-RagonC. PerrinG. RoulierP. GoutorbeP. LefrantJ.Y. WiramusS. JungB. PerbetS. HernuR. NauA. BaldesiO. Allardet-ServentJ. BaumstarckK. JouveE. MoussaM. HraiechS. GuervillyC. ForelJ.M. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: A randomized clinical trial.JAMA2013310161692170010.1001/jama.2013.280031 24108510
    [Google Scholar]
  48. GhaydaR.A. HanC.H. LeeK.H. KimJ.S. KimS.E. HongS.H. KimM. KronbichlerA. TizaouiK. LiH. KoyanagiA. JacobL. KimM.S. YonD.K. LeeS.W. KostevK. ShinJ.I. YangJ.W. SmithL. The effect of statins on mortality among patients with infection: Umbrella review of meta-analyses.Eur. Rev. Med. Pharmacol. Sci.202125626852695 33829455
    [Google Scholar]
  49. Meregildo-RodriguezE.D. Chunga-ChévezE.V. GianmarcoR.L. Vásquez-TiradoG.A. Further insights into to the role of statins against active tuberculosis: Systematic review and meta-analysis.Infez. Med.2022302194203 35693063
    [Google Scholar]
  50. LeeC.C. LeeM.G. HsuT.C. PortaL. ChangS.S. YoC.H. TsaiK.C. LeeM. A population-based cohort study on the drug-specific effect of statins on sepsis outcome.Chest2018153480581510.1016/j.chest.2017.09.024 28962887
    [Google Scholar]
  51. KrugerP. BaileyM. BellomoR. CooperD.J. HarwardM. HigginsA. HoweB. JonesD. JoyceC. KostnerK. McNeilJ. NicholA. RobertsM.S. SyresG. VenkateshB. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis.Am. J. Respir. Crit. Care Med.2013187774375010.1164/rccm.201209‑1718OC 23348980
    [Google Scholar]
  52. YuY. ZhuC. LiuC. GaoY. Effect of prior atorvastatin treatment on the frequency of hospital acquired pneumonia and evolution of biomarkers in patients with acute ischemic stroke: A multicenter prospective study.Biomed Res. Int.20172017564270410.1155/2017/5642704
    [Google Scholar]
  53. JiaM. HuangW. LiL. XuZ. WuL. Statins reduce mortality after non-severe but not after severe pneumonia: A systematic review and meta-analysis.J. Pharm. Pharm. Sci.201518328630210.18433/J34307 26517133
    [Google Scholar]
  54. JandaS. YoungA. FitzGeraldJ.M. EtminanM. SwistonJ. The effect of statins on mortality from severe infections and sepsis: A systematic review and meta-analysis.J Crit Care.2010254656. e7-e22
    [Google Scholar]
  55. MaY. WenX. PengJ. LuY. GuoZ. LuJ. Systematic review and meta-analysis on the association between outpatient statins use and infectious disease-related mortality.PLoS One2012712e5154810.1371/journal.pone.0051548 23284711
    [Google Scholar]
  56. CaffreyA.R. TimbrookT.T. NohE. SakoulasG. OpalS.M. NizetV. LaPlanteK.L. Evidence to support continuation of statin therapy in patients with Staphylococcus aureus bacteremia.Antimicrob. Agents Chemother.2017613e02228e1610.1128/AAC.02228‑16 28069650
    [Google Scholar]
  57. DeGorterM.K. TironaR.G. SchwarzU.I. ChoiY.H. DresserG.K. SuskinN. MyersK. ZouG. IwuchukwuO. WeiW.Q. WilkeR.A. HegeleR.A. KimR.B. Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care.Circ. Cardiovasc. Genet.20136440040810.1161/CIRCGENETICS.113.000099 23876492
    [Google Scholar]
  58. LinkE. ParishS. ArmitageJ. BowmanL. HeathS. MatsudaF. GutI. LathropM. CollinsR. SLCO1B1 variants and statin-induced myopathy--a genomewide study.N. Engl. J. Med.2008359878979910.1056/NEJMoa0801936 18650507
    [Google Scholar]
  59. HuS.Y. HsiehM.S. LinT.C. LiaoS.H. HsiehV.C.R. ChiangJ.H. ChangY.Z. Statins improve the long-term prognosis in patients who have survived sepsis.Medicine (Baltimore)20199817e1525310.1097/MD.0000000000015253 31027074
    [Google Scholar]
  60. Farghaly AlyU. AboutalebH.A. AbdellatifA.A.H. Sameh TolbaN. Formulation and evaluation of simvastatin polymeric nanoparticles loaded in hydrogel for optimum wound healing purpose.Drug Des. Devel. Ther.2019131567158010.2147/DDDT.S198413 31190737
    [Google Scholar]
  61. SamehN.F. AlyU. Abou TalebH.A. AbdellatifA.A.H. Prospective role of simvastatin on wound healing: Review of the literature.J. Bioequivalence Bioavailab.2018102364210.4172/0975‑0851.1000375
    [Google Scholar]
  62. LiuC. ZhuJ. HaiB. ZhangW. WangH. LengH. XuY. SongC. Single Intraosseous injection of simvastatin promotes endothelial progenitor cell mobilization, neovascularization, and wound healing in diabetic rats.Plast. Reconstr. Surg.2020145243344310.1097/PRS.0000000000006502 31985637
    [Google Scholar]
  63. SpampinatoS.F. CarusoG.I. De PasqualeR. SortinoM.A. MerloS. The treatment of impaired wound healing in diabetes: Looking among old drugs.Pharmaceuticals (Basel)20201346010.3390/ph13040060 32244718
    [Google Scholar]
  64. SalemH.F. NafadyM.M. EweesM.G.E.L.D. HassanH. KhallafR.A. Rosuvastatin calcium-based novel nanocubic vesicles capped with silver nanoparticles-loaded hydrogel for wound healing management: Optimization employing Box–Behnken design: In vitro and in vivo assessment.J. Liposome Res.2022321456110.1080/08982104.2020.1867166 33353435
    [Google Scholar]
  65. GuptaM. KumarA. Comparison of minimum inhibitory concentration (MIC) value of statin drugs: A systematic review.Antiinfect. Agents201817141910.2174/2211352516666180629124433
    [Google Scholar]
  66. WillisJ.A. CheburkanovV. ChenS. SoaresJ.M. KassabG. BlancoK.C. BagnatoV.S. de FigueiredoP. YakovlevV.V. Breaking down antibiotic resistance in methicillin-resistant Staphylococcus aureus: Combining antimicrobial photodynamic and antibiotic treatments.Proc. Natl. Acad. Sci. USA202211936e220837811910.1073/pnas.2208378119 36037346
    [Google Scholar]
  67. Al-KuraishyH.M. Al-GareebA.I. Al-BuhadilyA.K. Rosuvastatin as forthcoming antibiotic or as adjuvant additive agent: In vitro novel antibacterial study.J. Lab. Physicians201810327127510.4103/JLP.JLP_170_17 30078961
    [Google Scholar]
  68. KornelsenV. UngerM. KumarA. Atorvastatin does not display an antimicrobial activity on its own nor potentiates the activity of other antibiotics against Acinetobacter baumannii ATCC17978 or A. baumannii AB030.Access Microbiol.202131100028810.1099/acmi.0.000288 35018330
    [Google Scholar]
  69. FarmerA.R. MurrayC.K. MendeK. AkersK.S. ZeraW.C. BeckiusM.L. YunH.C. Effect of HMG-CoA reductase inhibitors on antimicrobial susceptibilities for gram-negative rods.J. Basic Microbiol.201353433633910.1002/jobm.201100614 22736455
    [Google Scholar]
  70. ManaloR.V.M. JosolV.J.D. GlorianiN.G. The differential effects of atorvastatin co-administered with ampicillin on the bacterial growth and biofilm formation of Staphylococcus aureus.Curr. Med. Res. Pract.20177517818310.1016/j.cmrp.2017.08.002
    [Google Scholar]
  71. SankarS. ThangamalaiR. PadmanabanS. KannanP. SrinivasanM. ArunamanC. In-vitro synergistic antibacterial effect of atorvastatin and ampicillin against resistant Staphylococcus spp and E. coli isolated from bovine mastitis.bioRxiv2019695817
    [Google Scholar]
  72. García-FernándezE. KochG. WagnerR.M. FeketeA. StengelS.T. SchneiderJ. Membrane microdomain disassembly inhibits MRSA antibiotic resistance.Cell201717161354136710.1016/j.cell.2017.10.012
    [Google Scholar]
  73. EvansM.D. SammelsonR. McDowellS. Differential effects of cotreatment of the antibiotic rifampin with host-directed therapeutics in reducing intracellular Staphylococcus aureus infection.PeerJ20208e1033010.7717/peerj.10330 33240647
    [Google Scholar]
  74. LobatoL.S. RosaP.S. FerreiraJ.S. NeumannA.S. da SilvaM.G. do NascimentoD.C. SoaresC.T. PedriniS.C.B. OliveiraD.S.L. MonteiroC.P. PereiraG.M.B. Ribeiro-AlvesM. HackerM.A. MoraesM.O. PessolaniM.C.V. DuarteR.S. LaraF.A. Statins increase rifampin mycobactericidal effect.Antimicrob. Agents Chemother.201458105766577410.1128/AAC.01826‑13 25049257
    [Google Scholar]
  75. SkerryC. PinnM.L. BruinersN. PineR. GennaroM.L. KarakousisP.C. Simvastatin increases the in vivo activity of the first-line tuberculosis regimen.J. Antimicrob. Chemother.20146992453245710.1093/jac/dku166 24855121
    [Google Scholar]
  76. AbdelazizA.A. El-BarrawyM.A. El-NagarR.A.M. Potent synergistic combination of rosuvastatin and levofloxacin against Staphylococcus aureus: In vitro and in vivo study.J. Appl. Microbiol.2021131118219610.1111/jam.14968 33326676
    [Google Scholar]
  77. ChoudhuryS. KannanK. Pule AddisonM. DarziS.A. SinghV. SinghT.U. ThangamalaiR. DashJ.R. ParidaS. DebroyB. PaulA. MishraS.K. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.Vascul. Pharmacol.20157113915010.1016/j.vph.2015.03.012 25869507
    [Google Scholar]
  78. SarkeshikianS.S. GhadirM.R. AlemiF. JalaliS.M. HormatiA. MohammadbeigiA. Atorvastatin in combination with conventional antimicrobial treatment of Helicobacter pylori eradication: A randomized controlled clinical trial.J. Gastroenterol. Hepatol.2020351717510.1111/jgh.14810 31359499
    [Google Scholar]
  79. RajabniaM. SadeghiA. AbdiS. GămanM-A. ZaliM.R. SalehiN. Effect of statins on Helicobacter pylori eradication rate: A systematic review and meta-analysis.GE Port. J. Gastroenterol.2022295322330
    [Google Scholar]
  80. FigueiredoE.P. RibeiroJ.M. NishioE.K. ScandorieiroS. CostaA.F. CardozoV.F. de OliveiraA.G. Durán, N.; Panagio, L.A.; Kobayashi, R.K.T.; Nakazato, G. New approach for simvastatin as an antibacterial: Synergistic effect with bio-synthesized silver nanoparticles against multidrug-resistant bacteria.Int. J. Nanomedicine2019147975798510.2147/IJN.S211756 31632012
    [Google Scholar]
  81. RampelottoR.F. LorenzoniV.V. SilvaD.C. MoraesG.A. SerafinM.B. TizottiM.K. CoelhoS. ZambiaziP. HörnerM. HörnerR. Synergistic antibacterial effect of statins with the complex [1-(4-bromophenyl)-3-phenyltriazene N3-oxide-κ 2N1, O4](dimethylbenzylamine-κ2C1, N4)spalladium(II).Braz. J. Pharm. Sci.20185425410.1590/s2175‑97902018000217369
    [Google Scholar]
  82. DominguesV.O. HörnerR. ReetzL.G.B. KuhnF. CoserV.M. RodriguesJ.N. BauchspiessR. PereiraW.V. ParaginskiG.L. LocatelliA. FankJ.O. GiglioV.F. HörnerM. In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells.J. Braz. Chem. Soc.201021122226223710.1590/S0103‑50532010001200009
    [Google Scholar]
  83. MohammadiA. Novel triazene dyes based on N-phenylpiperazine: Synthesis, anti-bacterial activity and solvatochromic properties.J. Mol. Liq.2014193697310.1016/j.molliq.2013.12.024
    [Google Scholar]
  84. LiuC.I. LiuG.Y. SongY. YinF. HenslerM.E. JengW.Y. NizetV. WangA.H.J. OldfieldE. A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence.Science200831958681391139410.1126/science.1153018 18276850
    [Google Scholar]
  85. ClauditzA. ReschA. WielandK.P. PeschelA. GötzF. Staphyloxanthin plays a role in the fitness of Staphylococcus aureus and its ability to cope with oxidative stress.Infect. Immun.20067484950495310.1128/IAI.00204‑06 16861688
    [Google Scholar]
  86. FriesenJ.A. RodwellV.W. The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases.Genome Biol.200451124810.1186/gb‑2004‑5‑11‑248 15535874
    [Google Scholar]
  87. HeustonS. BegleyM. GahanC.G.M. HillC. Isoprenoid biosynthesis in bacterial pathogens.Microbiology (Reading)201215861389140110.1099/mic.0.051599‑0 22466083
    [Google Scholar]
  88. ChowO.A. von Köckritz-BlickwedeM. BrightA.T. HenslerM.E. ZinkernagelA.S. CogenA.L. Statins enhance formation of phagocyte extracellular traps.Cell Host Microbe20108544545410.1016/j.chom.2010.10.005
    [Google Scholar]
  89. KoH.H.T. LareuR.R. DixB.R. HughesJ.D. In vitro antibacterial effects of statins against bacterial pathogens causing skin infections.Eur. J. Clin. Microbiol. Infect. Dis.20183761125113510.1007/s10096‑018‑3227‑5 29569046
    [Google Scholar]
  90. de JongeM.I. Pehau-ArnaudetG. FretzM.M. RomainF. BottaiD. BrodinP. HonoréN. MarchalG. JiskootW. EnglandP. ColeS.T. BroschR. ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity.J. Bacteriol.2007189166028603410.1128/JB.00469‑07 17557817
    [Google Scholar]
  91. PariharS.P. GulerR. KhutlangR. LangD.M. HurdayalR. MhlangaM.M. SuzukiH. MaraisA.D. BrombacherF. Statin therapy reduces the Mycobacterium tuberculosis burden in human macrophages and in mice by enhancing autophagy and phagosome maturation.J. Infect. Dis.2014209575476310.1093/infdis/jit550 24133190
    [Google Scholar]
  92. HaeriM.R. WhiteK. QharebeglouM. AnsarM.M. Cholesterol suppresses antimicrobial effect of statins.Iran. J. Basic Med. Sci.2015181212531256 26877857
    [Google Scholar]
  93. LiG. Intestinal probiotics: Interactions with bile salts and reduction of cholesterol.Procedia Environ. Sci.2012121180118610.1016/j.proenv.2012.01.405
    [Google Scholar]
  94. HildebrandtE. McGeeD.J. Helicobacter pylori lipopolysaccharide modification, Lewis antigen expression, and gastric colonization are cholesterol-dependent.BMC Microbiol.20099125810.1186/1471‑2180‑9‑258 20003432
    [Google Scholar]
  95. McGeeD.J. GeorgeA.E. TrainorE.A. HortonK.E. HildebrandtE. TestermanT.L. Cholesterol enhances Helicobacter pylori resistance to antibiotics and LL-37.Antimicrob. Agents Chemother.20115562897290410.1128/AAC.00016‑11 21464244
    [Google Scholar]
  96. SalihF.A. Inhibitory effect of Atorvastatin on the secretion of extracellular virulence products by Methicillin resistant Staphylococcus aureus.Zanco J. Pure Appl. Sci.20213348289
    [Google Scholar]
  97. LópezD. KolterR. Functional microdomains in bacterial membranes.Genes Dev.201024171893190210.1101/gad.1945010 20713508
    [Google Scholar]
  98. FosterT.J. Can β-lactam antibiotics be resurrected to combat MRSA?Trends Microbiol.2019271263810.1016/j.tim.2018.06.005 30031590
    [Google Scholar]
  99. HornM.P. KnechtS.M. RushingF.L. BirdsongJ. SiddallC.P. JohnsonC.M. AbrahamT.N. BrownA. VolkC.B. GammonK. BishopD.L. McKillipJ.L. McDowellS.A. Simvastatin inhibits Staphylococcus aureus host cell invasion through modulation of isoprenoid intermediates.J. Pharmacol. Exp. Ther.2008326113514310.1124/jpet.108.137927 18388257
    [Google Scholar]
  100. PrueferD. MakowskiJ. SchnellM. BuerkeU. DahmM. OelertH. SibeliusU. GrandelU. GrimmingerF. SeegerW. MeyerJ. DariusH. BuerkeM. Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin.Circulation2002106162104211010.1161/01.CIR.0000034048.38910.91 12379581
    [Google Scholar]
  101. HannachiN. FournierP.E. MartelH. HabibG. Camoin-JauL. Statins potentiate the antibacterial effect of platelets on Staphylococcus aureus.Platelets202132567167610.1080/09537104.2020.1792434 32664773
    [Google Scholar]
  102. YamazakiH. SuzukiM. AokiT. MorikawaS. MaejimaT. SatoF. SawanoboriK. KitaharaM. KodamaT. SaitoY. Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: Relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells.J. Atheroscler. Thromb.200613629530710.5551/jat.13.295 17192694
    [Google Scholar]
  103. MückA.O. SeegerH. WallwienerD. Class-specific pro-apoptotic effect of statins on human vascular endothelial cells.Z. Kardiol.200493539840210.1007/s00392‑004‑0081‑5 15160275
    [Google Scholar]
  104. Tapia-PérezJ.H. KirchesE. MawrinC. FirschingR. SchneiderT. Cytotoxic effect of different statins and thiazolidinediones on malignant glioma cells.Cancer Chemother. Pharmacol.20116751193120110.1007/s00280‑010‑1535‑2 21120479
    [Google Scholar]
  105. Björkhem-Bergman, L.; Lindh, J.D.; Bergman, P. What is a relevant statin concentration in cell experiments claiming pleiotropic effects?Br. J. Clin. Pharmacol.201172116416510.1111/j.1365‑2125.2011.03907.x 21223360
    [Google Scholar]
  106. HennessyE. AdamsC. ReenF.J. O’GaraF. Is there potential for repurposing statins as novel antimicrobials?Antimicrob. Agents Chemother.20166095111512110.1128/AAC.00192‑16 27324773
    [Google Scholar]
  107. BahramiA. ParsamaneshN. AtkinS.L. BanachM. SahebkarA. Effect of statins on toll-like receptors: A new insight to pleiotropic effects.Pharmacol. Res.201813523023810.1016/j.phrs.2018.08.014 30120976
    [Google Scholar]
  108. KandeloueiT. AbbasifardM. ImaniD. AslaniS. RaziB. FasihiM. ShafiekhaniS. MohammadiK. JamialahmadiT. ReinerŽ. SahebkarA. Effect of statins on serum level of hs-CRP and CRP in patients with cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.Med. Inflamm.2022873236010.1155/2022/8732360
    [Google Scholar]
  109. KoushkiK. ShahbazS.K. MashayekhiK. SadeghiM. ZayeriZ.D. TabaM.Y. BanachM. Al-RasadiK. JohnstonT.P. SahebkarA. Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-like receptor pathways.Clin. Rev. Allergy Immunol.202160217519910.1007/s12016‑020‑08791‑9 32378144
    [Google Scholar]
  110. MatsumotoM. EinhausD. GoldE.S. AderemA. Simvastatin augments lipopolysaccharide-induced proinflammatory responses in macrophages by differential regulation of the c-Fos and c-Jun transcription factors.J. Immunol.2004172127377738410.4049/jimmunol.172.12.7377 15187114
    [Google Scholar]
  111. ZeiserR. Immune modulatory effects of statins.Immunology20181541697510.1111/imm.12902 29392731
    [Google Scholar]
  112. GharehbeglouM. ArjmandG. HaeriM.R. KhazeniM. Nonselective mevalonate kinase inhibitor as a novel class of antibacterial agents.Cholesterol2015201514760110.1155/2015/147601
    [Google Scholar]
  113. CruszS.M. BalkwillF.R. Inflammation and cancer: Advances and new agents.Nat. Rev. Clin. Oncol.2015121058459610.1038/nrclinonc.2015.105 26122183
    [Google Scholar]
  114. Weitz-SchmidtG. Statins as anti-inflammatory agents.Trends Pharmacol. Sci.2002231048248710.1016/S0165‑6147(02)02077‑1 12368073
    [Google Scholar]
  115. NseirW. KhateebJ. TatourI. HaiekS. SamaraM. AssyN. Long-term statin therapy affects the severity of chronic gastritis.Helicobacter201015651051510.1111/j.1523‑5378.2010.00803.x 21073607
    [Google Scholar]
  116. AlmogY. Statins, inflammation, and sepsis.Hypothesis. Chest2003124274074310.1378/chest.124.2.740 12907568
    [Google Scholar]
  117. ArnaudC. MachF. Potential antiinflammatory and immunomodulatory effects of statins in rheumatologic therapy.Arthritis Rheum.200654239039210.1002/art.21757 16447215
    [Google Scholar]
  118. Braga FilhoJ.A.F. AbreuA.G. RiosC.E.P. Trovão, L.O.; Silva, D.L.F.; Cysne, D.N.; Nascimento, J.R.; Fortes, T.S.; Silva, L.A.; Guerra, R.N.M.; Maciel, M.C.G.; Serezani, C.H.; Nascimento, F.R.F. Prophylactic treatment with simvastatin modulates the immune response and increases animal survival following lethal sepsis infection.Front. Immunol.20189213710.3389/fimmu.2018.02137 30298072
    [Google Scholar]
  119. McDowellS.A. MaY. KusanoR. AkinbiH.T. Simvastatin is protective during Staphylococcus aureus pneumonia.Curr. Pharm. Biotechnol.20111291455146210.2174/138920111798281027 21401521
    [Google Scholar]
  120. DeepeG.S.Jr BuesingW.R. Deciphering the pathways of death of Histoplasma capsulatum-infected macrophages: Implications for the immunopathogenesis of early infection.J. Immunol.2012188133434410.4049/jimmunol.1102175 22102723
    [Google Scholar]
  121. GyetvaiA. EmriT. TakácsK. DergezT. FeketeA. PestiM. PócsiI. LenkeyB. Lovastatin possesses a fungistatic effect against Candida albicans, but does not trigger apoptosis in this opportunistic human pathogen.FEMS Yeast Res.2006681140114810.1111/j.1567‑1364.2006.00097.x 17156011
    [Google Scholar]
  122. del RealG. Jiménez-BarandaS. MiraE. LacalleR.A. LucasP. Gómez-MoutónC. AlegretM. PeñaJ.M. Rodríguez-ZapataM. Alvarez-MonM. Martínez-AC. MañesS. Statins inhibit HIV-1 infection by down-regulating Rho activity.J. Exp. Med.2004200454154710.1084/jem.20040061 15314078
    [Google Scholar]
  123. CinesD.B. PollakE.S. BuckC.A. LoscalzoJ. ZimmermanG.A. McEverR.P. PoberJ.S. WickT.M. KonkleB.A. SchwartzB.S. BarnathanE.S. McCraeK.R. HugB.A. SchmidtA.M. SternD.M. Endothelial cells in physiology and in the pathophysiology of vascular disorders.Blood1998911035273561 9572988
    [Google Scholar]
  124. JainM.K. RidkerP.M. Anti-inflammatory effects of statins: Clinical evidence and basic mechanisms.Nat. Rev. Drug Discov.200541297798710.1038/nrd1901 16341063
    [Google Scholar]
  125. LawsM. ShaabanA. RahmanK.M. Antibiotic resistance breakers: Current approaches and future directions.FEMS Microbiol. Rev.201943549051610.1093/femsre/fuz014 31150547
    [Google Scholar]
  126. AnderssonD.I. BalabanN.Q. BaqueroF. CourvalinP. GlaserP. GophnaU. KishonyR. MolinS. TønjumT. Antibiotic resistance: Turning evolutionary principles into clinical reality.FEMS Microbiol. Rev.202044217118810.1093/femsre/fuaa001 31981358
    [Google Scholar]
  127. RolainJ.M. Food and human gut as reservoirs of transferable antibiotic resistance encoding genes.Front. Microbiol.2013417310.3389/fmicb.2013.00173 23805136
    [Google Scholar]
  128. SommerM.O.A. DantasG. ChurchG.M. Functional characterization of the antibiotic resistance reservoir in the human microflora.Science200932559441128113110.1126/science.1176950 19713526
    [Google Scholar]
  129. Le BastardQ. Al-GhalithG.A. GrégoireM. ChapeletG. JavaudinF. DaillyE. BatardE. KnightsD. MontassierE. Systematic review: Human gut dysbiosis induced by non-antibiotic prescription medications.Aliment. Pharmacol. Ther.201847333234510.1111/apt.14451 29205415
    [Google Scholar]
  130. ZhaoC. HuY. ChenH. LiB. CaoL. XiaJ. YinY. An in vitro evaluation of the effects of different statins on the structure and function of human gut bacterial community.PLoS One2020153e023020010.1371/journal.pone.0230200 32214324
    [Google Scholar]
  131. Le RoyC. BowyerR. CarrV. CosteiraR. Castillo-FernandezJ. MartinT. Host genetic and environmental factors shape the human gut resistome.BioRxiv202010.1101/2020.05.18.092973
    [Google Scholar]
  132. MahboobiS.K. ShohatE.Z. JellinekS.P. RoseM. Systemic infections can decrease the threshold of statin-induced muscle injury.South. Med. J.200699440340410.1097/01.smj.0000209273.52754.86 16634254
    [Google Scholar]
  133. VincentA. MillerJ.A.L. Statins for sepsis: A cautionary note.Intensive Care Med.200632579510.1007/s00134‑006‑0143‑4 16550367
    [Google Scholar]
  134. GolombB.A. EvansM.A. Statin adverse effects: A review of the literature and evidence for a mitochondrial mechanism.Am. J. Cardiovasc. Drugs20088637341810.2165/0129784‑200808060‑00004 19159124
    [Google Scholar]
  135. BrealeyD.A. SingerM. TerblancheM. Potential metabolic consequences of statins in sepsis.Crit. Care Med.20113961514152010.1097/CCM.0b013e31820eb74f 21317651
    [Google Scholar]
  136. KellickK.A. BottorffM. TothP.P. A clinician’s guide to statin drug-drug interactions.J. Clin. Lipid.201483S30S46
    [Google Scholar]
  137. LeeA.J. MaddixD.S. Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin.Ann. Pharmacother.2001351263110.1345/aph.10177 11197581
    [Google Scholar]
  138. PatelA.M. ShariffS. BaileyD.G. JuurlinkD.N. GandhiS. MamdaniM. GomesT. FleetJ. HwangY.J. GargA.X. Statin toxicity from macrolide antibiotic coprescription: A population-based cohort study.Ann. Intern. Med.20131581286987610.7326/0003‑4819‑158‑12‑201306180‑00004 23778904
    [Google Scholar]
  139. AlzahraniT. LiappisA.P. BaddourL.M. KarasikP.E. Statin use and the risk of cardiovascular implantable electronic device infection: A cohort study in a veteran population.Pacing Clin. Electrophysiol.201841328428910.1111/pace.13285 29341172
    [Google Scholar]
  140. CobanA.Y. TekeliH.O. GüneyA.K. DurupinarB. Investigation of the in vitro antibacterial effects of statins.Mikrobiyol. Bul.2010441161163 20455414
    [Google Scholar]
  141. MatznellerP. ManafiM. ZeitlingerM. Antimicrobial effect of statins: Organic solvents might falsify microbiological testing results.Int. J. Clin. Pharmacol. Ther.2011491166667110.5414/CP201581 22011691
    [Google Scholar]
  142. TingM. WhitakerE.J. AlbandarJ.M. Systematic review of the in vitro effects of statins on oral and perioral microorganisms.Eur. J. Oral Sci.2016124141010.1111/eos.12239 26718458
    [Google Scholar]
  143. QuiveyR. Reducing dental caries.WS20140186271A12012
  144. RadwanS. EzzatO. Antimicrobial effect and immunomodulation of atorvastatin.J. Am. Sci.20128910121016http://www.jofamericanscience.org/
    [Google Scholar]
  145. AlshammariA. In vitro effect of statins on Streptococcus mutans, Streptococcus sanguis, and Streptococcus salvarius.Temple University2016
    [Google Scholar]
  146. SarabhaiS. DhaliwalL.K. CapalashN. SharmaP. Effect of atorvastatin and rosuvastatin on quorum sensing, biofilm formation and bacterial motilities of Pseudomonas aeruginosa.Int. J. Pharma Bio Sci.20156118https://www.cabidigitallibrary.org/doi/full/10.5555/20153166522
    [Google Scholar]
/content/journals/cmc/10.2174/0929867331666230829141301
Loading
/content/journals/cmc/10.2174/0929867331666230829141301
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): Antibacterial resistance; antimicrobial; atorvastatin; MICs; simvastatin; statins
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test