Abstract
Staphylococcus aureus is a leading cause of septicemia, endocarditis, pneumonia, skin and soft tissue infections, bone and joint infections, and hospital-acquired infections. In particular, methicillin-resistant Staphylococcus aureus (MRSA) is associated with high morbidity and mortality, and continues to be a major public health problem. The emergence of multidrug-resistant MRSA strains along with the wide consumption of antibiotics has made anti-MRSA treatment a huge challenge. Novel treatment strategies (e.g., novel antimicrobials and new administrations) against MRSA are urgently needed. In the past decade, pharmaceutical companies have invested more in the research and development (R&D) of new antimicrobials and strategies, spurred by favorable policies. All research articles were collected from authentic online databases, including Google Scholar, PubMed, Scopus, and Web of Science, by using different combinations of keywords, including ‘anti-MRSA’, ‘antibiotic’, ‘antimicrobial’, ‘clinical trial’, ‘clinical phase’, clinical studies’, and ‘pipeline’. The information extracted from articles was compared to information provided on the drug manufacturer’s website and Clinical Trials.gov (https://clinicaltrials.gov/) to confirm the latest development phase of anti-MRSA agents. The present review focuses on the current development status of new anti-MRSA strategies concerning chemistry, pharmacological target(s), indications, route of administration, efficacy and safety, pharmacokinetics, and pharmacodynamics, and aims to discuss the challenges and opportunities in developing drugs for anti-MRSA infections.
[http://dx.doi.org/10.3389/fmolb.2021.654038] [PMID: 33996906]
[http://dx.doi.org/10.1001/jama.299.10.1190] [PMID: 18334697]
[http://dx.doi.org/10.1186/s13059-017-1252-9] [PMID: 28724393]
[PMID: 21165342]
[http://dx.doi.org/10.1038/sj.eye.6701465] [PMID: 15375372]
[http://dx.doi.org/10.1021/ja8029448] [PMID: 18582062]
[http://dx.doi.org/10.5144/0256-4947.2012.513] [PMID: 22871621]
[PMID: 20090137]
[http://dx.doi.org/10.1016/j.ijantimicag.2011.09.030] [PMID: 22230333]
[http://dx.doi.org/10.1056/NEJM200101043440102] [PMID: 11136954]
[http://dx.doi.org/10.1128/JCM.02423-12] [PMID: 23135945]
[http://dx.doi.org/10.1128/CMR.00020-18] [PMID: 30209034]
[http://dx.doi.org/10.1371/journal.pone.0092760] [PMID: 24755631]
[http://dx.doi.org/10.1088/1752-7155/8/4/041001] [PMID: 25307159]
[http://dx.doi.org/10.3201/eid0702.010237] [PMID: 11294734]
[http://dx.doi.org/10.4103/jms.jms_25_17]
[http://dx.doi.org/10.1080/13543784.2020.1750595] [PMID: 32242469]
[http://dx.doi.org/10.1093/jac/dkl393] [PMID: 17040922]
[http://dx.doi.org/10.1001/jama.298.15.1826] [PMID: 17940240]
[http://dx.doi.org/10.1016/S0195-6701(03)00147-6] [PMID: 12855234]
[http://dx.doi.org/10.1016/j.ijantimicag.2008.05.007] [PMID: 18701261]
[http://dx.doi.org/10.1517/17460441.2013.807246] [PMID: 23829425]
[PMID: 18666036]
[http://dx.doi.org/10.1592/phco.24.1.41.34802] [PMID: 14740787]
[http://dx.doi.org/10.1016/j.jinf.2007.05.180] [PMID: 17629567]
[http://dx.doi.org/10.1086/504084] [PMID: 16652325]
[http://dx.doi.org/10.2174/1389200216666151001121004] [PMID: 26424176]
[http://dx.doi.org/10.1185/03007990903512057] [PMID: 20055750]
[http://dx.doi.org/10.1080/08998280.2006.11928154] [PMID: 16609746]
[http://dx.doi.org/10.3122/jabfm.2010.06.090270] [PMID: 21057066]
[http://dx.doi.org/10.1086/525536] [PMID: 18197761]
[http://dx.doi.org/10.1086/519470] [PMID: 17712746]
[http://dx.doi.org/10.1080/14740338.2019.1621288] [PMID: 31106600]
[http://dx.doi.org/10.1089/107662903322762833] [PMID: 15000746]
[http://dx.doi.org/10.1128/AAC.50.4.1581-1585.2006] [PMID: 16569891]
[http://dx.doi.org/10.1086/420818] [PMID: 15227611]
[http://dx.doi.org/10.1007/s10156-012-0501-9] [PMID: 23085743]
[http://dx.doi.org/10.4088/PCC.09r00853] [PMID: 20098528]
[http://dx.doi.org/10.1177/0091270007300263] [PMID: 17519399]
[http://dx.doi.org/10.1016/S1068-607X(02)00113-0]
[http://dx.doi.org/10.1086/367662] [PMID: 12567306]
[http://dx.doi.org/10.1371/journal.pone.0230383] [PMID: 32191760]
[http://dx.doi.org/10.1093/jac/dkw333] [PMID: 27585969]
[http://dx.doi.org/10.1086/655827] [PMID: 20695801]
[http://dx.doi.org/10.1016/j.jaip.2016.03.008] [PMID: 27130709]
[http://dx.doi.org/10.1155/1998/538090] [PMID: 22346533]
[http://dx.doi.org/10.1099/jmm.0.45610-0] [PMID: 15314196]
[http://dx.doi.org/10.1056/NEJMoa1403789] [PMID: 25785967]
[http://dx.doi.org/10.1136/bmj.k341] [PMID: 29438980]
[http://dx.doi.org/10.1056/NEJMoa1507476] [PMID: 26962903]
[http://dx.doi.org/10.1128/AAC.03688-14] [PMID: 25421472]
[http://dx.doi.org/10.1016/S0924-8579(98)00025-9] [PMID: 9716291]
[http://dx.doi.org/10.1056/NEJMoa1310480] [PMID: 24897082]
[http://dx.doi.org/10.1016/j.ijantimicag.2017.11.008] [PMID: 29180276]
[http://dx.doi.org/10.1086/587896] [PMID: 18444791]
[http://dx.doi.org/10.1086/341026] [PMID: 12145720]
[http://dx.doi.org/10.1111/j.1742-1241.1998.tb11567.x] [PMID: 9624783]
[http://dx.doi.org/10.1007/s15010-009-8468-x] [PMID: 19768381]
[http://dx.doi.org/10.1016/j.clinthera.2005.09.005] [PMID: 16291409]
[http://dx.doi.org/10.1086/380125] [PMID: 14679454]
[http://dx.doi.org/10.1007/s10156-007-0521-Z] [PMID: 17593499]
[http://dx.doi.org/10.1128/AAC.00194-12] [PMID: 22585222]
[http://dx.doi.org/10.1128/AAC.03513-14] [PMID: 25331699]
[http://dx.doi.org/10.1007/s00018-011-0717-3] [PMID: 21598022]
[http://dx.doi.org/10.2147/IDR.S49229] [PMID: 25210467]
[http://dx.doi.org/10.3389/fimmu.2020.02177] [PMID: 33072081]
[http://dx.doi.org/10.1021/jm200450h] [PMID: 21732630]
[http://dx.doi.org/10.1016/j.addr.2020.12.016] [PMID: 33400958]
[http://dx.doi.org/10.1111/lam.12792] [PMID: 28802058]
[http://dx.doi.org/10.1002/pep2.24122]
[http://dx.doi.org/10.1517/13543784.2014.848853] [PMID: 24215473]
[http://dx.doi.org/10.1021/acscombsci.8b00088] [PMID: 30372025]
[http://dx.doi.org/10.1089/jop.2015.0098] [PMID: 26501484]
[http://dx.doi.org/10.3389/fnins.2017.00073] [PMID: 28261050]
[http://dx.doi.org/10.1093/cid/cit152] [PMID: 23599308]
[http://dx.doi.org/10.1080/13543776.2020.1740683] [PMID: 32149532]
[http://dx.doi.org/10.4155/fmc.12.213] [PMID: 23464521]
[http://dx.doi.org/10.12703/P5-51] [PMID: 24381727]
[http://dx.doi.org/10.1186/s12879-016-2100-3] [PMID: 28061827]
[http://dx.doi.org/10.1038/ja.2017.117] [PMID: 29066797]
[http://dx.doi.org/10.1128/AAC.00267-19] [PMID: 31182524]
[http://dx.doi.org/10.3390/microorganisms8020191] [PMID: 32019171]
[http://dx.doi.org/10.26717/BJSTR.2018.07.001536]
[http://dx.doi.org/10.1093/jac/dks213] [PMID: 22687888]
[http://dx.doi.org/10.3390/antibiotics2040500] [PMID: 27029317]
[http://dx.doi.org/10.1128/AAC.48.8.3188-3192.2004] [PMID: 15273148]
[http://dx.doi.org/10.1080/13543784.2017.1385761] [PMID: 28952384]
[http://dx.doi.org/10.1016/j.mib.2011.08.002] [PMID: 21873107]
[http://dx.doi.org/10.1016/j.jmii.2019.05.015]
[http://dx.doi.org/10.1128/AAC.02095-16] [PMID: 28373199]
[http://dx.doi.org/10.1128/AAC.00723-10] [PMID: 20855730]
[http://dx.doi.org/10.1517/13543784.2016.1109077] [PMID: 26536498]
[http://dx.doi.org/10.1128/AAC.00451-18]
[http://dx.doi.org/10.1128/AAC.01195-20] [PMID: 32778552]
[http://dx.doi.org/10.1002/cbdv.201800560] [PMID: 30467968]
[http://dx.doi.org/10.1128/CMR.00033-13] [PMID: 24092856]
[http://dx.doi.org/10.1101/cshperspect.a027110] [PMID: 27742734]
[http://dx.doi.org/10.1039/C6MD00232C] [PMID: 27642504]
[http://dx.doi.org/10.1080/14787210.2019.1667229] [PMID: 31553250]
[http://dx.doi.org/10.1080/17460441.2016.1187597] [PMID: 27169483]
[http://dx.doi.org/10.1128/AAC.05532-11] [PMID: 22203585]
[http://dx.doi.org/10.1128/AAC.00452-10] [PMID: 20585126]
[http://dx.doi.org/10.1128/AAC.05382-11] [PMID: 22155835]
[http://dx.doi.org/10.1021/acs.joc.7b02318] [PMID: 29019678]
[http://dx.doi.org/10.1021/ja970895o]
[http://dx.doi.org/10.1038/ja.2011.9] [PMID: 21326252]
[http://dx.doi.org/10.3389/fmicb.2019.01230] [PMID: 31275253]
[http://dx.doi.org/10.1128/AAC.01741-15] [PMID: 26711777]
[http://dx.doi.org/10.1038/s41429-020-0291-8] [PMID: 32152527]
[http://dx.doi.org/10.1016/j.diagmicrobio.2020.115040] [PMID: 32354459]
[http://dx.doi.org/10.1097/QCO.0000000000000539] [PMID: 30950853]
[http://dx.doi.org/10.1128/AAC.02588-18] [PMID: 30910894]
[http://dx.doi.org/10.1093/cid/cir170] [PMID: 21546632]
[http://dx.doi.org/10.1016/j.diagmicrobio.2009.10.014] [PMID: 20159376]
[http://dx.doi.org/10.1128/AAC.03389-14] [PMID: 24957822]
[http://dx.doi.org/10.1517/14728214.2013.813480] [PMID: 23848400]
[http://dx.doi.org/10.1128/AAC.01159-10] [PMID: 21245439]
[PMID: 20112172]
[http://dx.doi.org/10.1128/AAC.01464-15] [PMID: 26259789]
[http://dx.doi.org/10.1038/s41579-020-0340-0] [PMID: 32152509]
[http://dx.doi.org/10.4155/fmc-2020-0225] [PMID: 33169622]
[http://dx.doi.org/10.1128/AAC.00708-15] [PMID: 26033735]
[http://dx.doi.org/10.1128/AAC.01779-12] [PMID: 23403431]
[http://dx.doi.org/10.1128/AAC.03360-14] [PMID: 25136015]
[http://dx.doi.org/10.3390/antibiotics9070418] [PMID: 32708925]
[http://dx.doi.org/10.1016/j.mib.2021.02.001] [PMID: 33662818]
[http://dx.doi.org/10.1128/JCM.03117-20] [PMID: 33910968]
[http://dx.doi.org/10.1128/AAC.01078-19] [PMID: 31332073]
[http://dx.doi.org/10.1128/AAC.00731-18] [PMID: 30038042]
[http://dx.doi.org/10.1128/JCM.00229-19] [PMID: 31092596]
[http://dx.doi.org/10.1111/1440-1681.12613] [PMID: 27341401]
[http://dx.doi.org/10.1093/jac/dky365] [PMID: 30215762]
[http://dx.doi.org/10.1080/21505594.2017.1295205] [PMID: 28267417]
[http://dx.doi.org/10.1371/journal.pone.0190537] [PMID: 29364906]
[http://dx.doi.org/10.1517/13543784.2016.1168803] [PMID: 26998623]
[http://dx.doi.org/10.3390/antib7010005] [PMID: 31544858]
[http://dx.doi.org/10.1007/s40265-020-01402-z] [PMID: 32951149]
[http://dx.doi.org/10.1128/AAC.00357-16] [PMID: 27324766]
[http://dx.doi.org/10.1016/S1473-3099(20)30995-6] [PMID: 33894131]
[http://dx.doi.org/10.1517/14656566.7.14.1957] [PMID: 17020421]
[PMID: 33307757]
[http://dx.doi.org/10.4103/ijmm.IJMM_20_307] [PMID: 33154240]
[http://dx.doi.org/10.1016/j.ijmmb.2022.11.005] [PMID: 36509611]
[http://dx.doi.org/10.1128/AAC.02297-17] [PMID: 29263070]
[http://dx.doi.org/10.2147/IDR.S105620] [PMID: 27354817]
[http://dx.doi.org/10.1128/AAC.05044-11] [PMID: 21947389]
[http://dx.doi.org/10.1186/s12941-016-0150-4] [PMID: 27215369]
[http://dx.doi.org/10.1016/j.jmii.2018.11.006] [PMID: 30616912]
[http://dx.doi.org/10.1586/14787210.2014.894881] [PMID: 24579813]
[http://dx.doi.org/10.1128/AAC.00078-09] [PMID: 19738018]
[http://dx.doi.org/10.1016/j.jmii.2015.09.005] [PMID: 26748734]
[http://dx.doi.org/10.1128/AAC.46.4.1080-1085.2002] [PMID: 11897593]
[http://dx.doi.org/10.1016/j.clinthera.2018.10.007] [PMID: 30420289]
[http://dx.doi.org/10.1002/med.21798] [PMID: 33645845]
[http://dx.doi.org/10.1016/j.trsl.2020.03.007] [PMID: 32275897]
[http://dx.doi.org/10.1016/j.clinthera.2018.11.009] [PMID: 30559004]
[http://dx.doi.org/10.3390/app10072211]
[PMID: 27999047]
[http://dx.doi.org/10.2147/DDDT.S229882] [PMID: 31920285]
[http://dx.doi.org/10.1128/AAC.04039-14] [PMID: 25534726]
[http://dx.doi.org/10.3109/00498254.2015.1112933] [PMID: 26586303]
[http://dx.doi.org/10.1093/jac/dkx367] [PMID: 29069400]
[http://dx.doi.org/10.1128/AAC.02181-16] [PMID: 28167545]
[http://dx.doi.org/10.1093/jac/dkv442] [PMID: 26747098]
[http://dx.doi.org/10.1128/AAC.48.7.2570-2575.2004] [PMID: 15215110]
[http://dx.doi.org/10.1128/AAC.00712-12] [PMID: 22869571]
[http://dx.doi.org/10.2217/17460913.4.2.131] [PMID: 19257839]
[http://dx.doi.org/10.1080/19420862.2016.1229722] [PMID: 27653831]
[http://dx.doi.org/10.1093/cid/cir174] [PMID: 21546627]
[http://dx.doi.org/10.1128/AAC.00587-06] [PMID: 17065630]
[http://dx.doi.org/10.1128/AAC.50.1.243-249.2006] [PMID: 16377693]
[http://dx.doi.org/10.1002/jcph.150] [PMID: 23907665]
[http://dx.doi.org/10.26226/morressier.56ebbf52d462b80296c97eca]
[http://dx.doi.org/10.1128/AAC.02629-16] [PMID: 28348152]
[http://dx.doi.org/10.1093/ofid/ofw172.1533]
[http://dx.doi.org/10.1007/s00134-018-5229-2] [PMID: 30343314]
[PMID: 27795368]
[http://dx.doi.org/10.1002/ardp.202200214] [PMID: 35841594]
[http://dx.doi.org/10.1128/JCM.01643-09] [PMID: 19846653]
[http://dx.doi.org/10.1021/acs.chemrestox.0c00524] [PMID: 33913699]
[http://dx.doi.org/10.1128/AAC.02158-19] [PMID: 32229495]
[http://dx.doi.org/10.1016/j.jpba.2017.01.041] [PMID: 28279932]
[http://dx.doi.org/10.4103/2229-516X.112229] [PMID: 23776832]
[http://dx.doi.org/10.1177/0009922807307186] [PMID: 18354031]
[http://dx.doi.org/10.1038/srep39004] [PMID: 27958389]
[http://dx.doi.org/10.1039/C8NP00042E] [PMID: 29979463]
[http://dx.doi.org/10.3390/molecules22060996] [PMID: 28617344]
[http://dx.doi.org/10.1016/j.bmcl.2020.126969] [PMID: 32014384]
[http://dx.doi.org/10.1002/phar.2166] [PMID: 30019769]
[http://dx.doi.org/10.1007/s11908-020-00732-z] [PMID: 32834786]
[http://dx.doi.org/10.1007/s40265-020-01443-4] [PMID: 33247830]
[http://dx.doi.org/10.3390/microorganisms7100386] [PMID: 31554342]
[http://dx.doi.org/10.1345/aph.1L016] [PMID: 18477729]
[http://dx.doi.org/10.2165/00128071-200809040-00004] [PMID: 18572975]
[http://dx.doi.org/10.1128/AAC.00551-07] [PMID: 17954698]
[http://dx.doi.org/10.1086/526527] [PMID: 18225981]
[http://dx.doi.org/10.1128/AAC.02367-19] [PMID: 32661000]
[http://dx.doi.org/10.1080/00498254.2020.1756007] [PMID: 32283993]
[http://dx.doi.org/10.1111/cts.12594] [PMID: 30369076]
[http://dx.doi.org/10.1016/j.jmii.2017.07.011] [PMID: 30181096]
[http://dx.doi.org/10.1016/j.clinthera.2019.04.025] [PMID: 31126694]
[http://dx.doi.org/10.1517/14740338.2016.1142528] [PMID: 26764972]
[http://dx.doi.org/10.1093/cid/ciz090] [PMID: 30722059]
[http://dx.doi.org/10.1093/cid/ciaa974] [PMID: 32897367]
[http://dx.doi.org/10.1074/jbc.M113.532804] [PMID: 24739388]
[http://dx.doi.org/10.1128/AAC.00250-20] [PMID: 32747361]
[http://dx.doi.org/10.1016/j.jgar.2019.09.017] [PMID: 31600598]
[http://dx.doi.org/10.1128/AAC.01383-08] [PMID: 19414572]
[http://dx.doi.org/10.1093/ofid/ofw172.1057]
[http://dx.doi.org/10.1016/j.ijmm.2013.08.009] [PMID: 24119568]
[http://dx.doi.org/10.1111/1751-7915.13484] [PMID: 31520522]
[http://dx.doi.org/10.1038/ja.2011.44] [PMID: 21587262]
[http://dx.doi.org/10.1016/j.coph.2012.07.004] [PMID: 22841284]
[http://dx.doi.org/10.1016/j.ijantimicag.2010.02.008] [PMID: 20346634]
[http://dx.doi.org/10.1080/14787210.2019.1604220] [PMID: 31012332]
[http://dx.doi.org/10.1093/jac/dkm409] [PMID: 17962215]
[http://dx.doi.org/10.1517/13543784.16.9.1441] [PMID: 17714029]
[http://dx.doi.org/10.1345/aph.1L167] [PMID: 19435963]
[http://dx.doi.org/10.1021/acs.jmedchem.6b00485] [PMID: 27336583]
[PMID: 34365945]
[http://dx.doi.org/10.1093/jac/dkm236] [PMID: 17606482]
[http://dx.doi.org/10.1016/S0732-8893(99)00104-2] [PMID: 10744365]
[http://dx.doi.org/10.1128/AAC.48.12.4754-4761.2004] [PMID: 15561853]
[http://dx.doi.org/10.1128/AAC.00162-11] [PMID: 21555765]
[http://dx.doi.org/10.1128/AAC.01285-10] [PMID: 21149626]
[http://dx.doi.org/10.1093/jac/dks307] [PMID: 22875850]
[http://dx.doi.org/10.1080/14787210.2018.1536545] [PMID: 30317894]
[http://dx.doi.org/10.1007/s11274-014-1720-2] [PMID: 25129332]
[http://dx.doi.org/10.1128/AAC.00468-17] [PMID: 28483959]
[http://dx.doi.org/10.1128/AAC.01672-10] [PMID: 21343445]
[http://dx.doi.org/10.1128/AAC.01383-07] [PMID: 18316525]
[http://dx.doi.org/10.1128/AAC.02566-12] [PMID: 23478958]
[http://dx.doi.org/10.1021/acs.jmedchem.0c01328] [PMID: 33325700]
[http://dx.doi.org/10.1128/AAC.05789-11] [PMID: 22232289]
[http://dx.doi.org/10.1128/AAC.01118-16] [PMID: 27671070]
[http://dx.doi.org/10.1038/srep35442] [PMID: 27739497]
[http://dx.doi.org/10.1097/QCO.0000000000000708] [PMID: 33395093]
[http://dx.doi.org/10.1042/BCJ20200610] [PMID: 33881487]
[http://dx.doi.org/10.1038/nature16057] [PMID: 26536114]
[http://dx.doi.org/10.1038/nchem.2635] [PMID: 27874860]
[PMID: 31559785]
[http://dx.doi.org/10.1016/j.bmcl.2015.06.057] [PMID: 26141771]
[http://dx.doi.org/10.1016/j.ejmech.2013.01.048] [PMID: 23501109]
[http://dx.doi.org/10.2217/fmb.15.115] [PMID: 26573022]
[http://dx.doi.org/10.1128/AAC.01562-06] [PMID: 17420210]
[http://dx.doi.org/10.1016/j.ejps.2017.08.002] [PMID: 28782609]
[http://dx.doi.org/10.1128/AAC.01690-15] [PMID: 26324261]
[http://dx.doi.org/10.1016/j.bmcl.2003.07.023] [PMID: 14623005]
[http://dx.doi.org/10.3389/fchem.2021.659845] [PMID: 33996753]
[http://dx.doi.org/10.3390/ijms22020617] [PMID: 33435500]
[http://dx.doi.org/10.1021/acs.jcim.8b00105] [PMID: 30040885]
[http://dx.doi.org/10.1021/acs.accounts.0c00894] [PMID: 33792282]
[http://dx.doi.org/10.3390/antibiotics9090621] [PMID: 32961696]
[http://dx.doi.org/10.1128/AAC.02723-20] [PMID: 34228536]
[PMID: 18472990]
[http://dx.doi.org/10.2217/fmb.10.155] [PMID: 21162635]
[http://dx.doi.org/10.1080/17512433.2019.1619454] [PMID: 31092053]
[http://dx.doi.org/10.1016/j.diagmicrobio.2021.115471] [PMID: 34280671]
[http://dx.doi.org/10.1016/j.cmi.2017.02.035] [PMID: 28274770]
[http://dx.doi.org/10.3201/eid1206.051141] [PMID: 16707043]
[http://dx.doi.org/10.3390/vaccines9020151] [PMID: 33668613]
[http://dx.doi.org/10.1016/j.drudis.2020.10.011] [PMID: 33091564]
[http://dx.doi.org/10.1038/nrmicro821] [PMID: 15040259]
[http://dx.doi.org/10.1111/j.2042-7158.2010.01183.x] [PMID: 21155818]
[http://dx.doi.org/10.1016/j.drudis.2012.03.012] [PMID: 22480870]
[http://dx.doi.org/10.1021/acs.nanolett.8b01000] [PMID: 29902011]
[http://dx.doi.org/10.1371/journal.pcbi.1007087] [PMID: 31295255]
[http://dx.doi.org/10.3389/fmicb.2017.01917] [PMID: 29046671]
[http://dx.doi.org/10.4155/fmc-2017-0199] [PMID: 29569952]
[http://dx.doi.org/10.3390/antibiotics9020065] [PMID: 32041137]
[http://dx.doi.org/10.1086/506568] [PMID: 16886141]
[http://dx.doi.org/10.1093/jac/dkr437] [PMID: 22010206]
[http://dx.doi.org/10.1038/ja.2013.86] [PMID: 24002361]
[http://dx.doi.org/10.1016/S0924-8579(07)00158-6] [PMID: 17659208]
[http://dx.doi.org/10.1517/14728222.9.2.253] [PMID: 15934914]