In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid

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w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Original

article

In

vitro

susceptibility

of

methicillin-resistant

Staphylococcus

aureus

isolates

from

skin

and

soft

tissue

infections

to

vancomycin,

daptomycin,

linezolid

and

tedizolid

Johanna

Marcela

Vanegas

Múnera,

Ana

María

Ocampo

Ríos,

Daniela

Montoya

Urrego,

Judy

Natalia

Jiménez

Quiceno

∗

UniversidaddeAntioquia,EscueladeMicrobiología,GrupodeMicrobiologíaBásicayAplicada,Medellín,Colombia

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received23November2016 Accepted23March2017 Availableonline19April2017

Keywords:

MRSA

Skinandsofttissuesinfections Tedizolid

Linezolid Vancomycin Daptomycin

a

b

s

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Introduction:Treatmentofmultidrug-resistantGram-positiveinfectionscausedby Staphy-lococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms.Tedizolidisanext-generationoxazolidinone,recentlyapprovedforskinand softtissuesinfections.Weconductedastudytodetermineinvitrosusceptibilityto van-comycin,daptomycin,linezolidandtedizolidinMRSAclinicalisolatesfromadultpatients withskinandsofttissueinfections.

Materialandmethods: Methicillin-resistantS.aureusisolateswerecollectedinthree tertiary-carehospitalsofMedellin,Colombia,fromFebruary2008toJune2010aspartofaprevious study.ClinicalcharacteristicswereassessedbymedicalrecordsandMICvalueswere deter-mined by Epsilometertest.Genotypicanalysisincluded spatyping, MLST,andSCCmec typing.

Results:A totalof150MRSAisolateswereevaluated andtedizolidMICvalues obtained showed higherinvitroactivitythanother antimicrobials,withMICvaluesrangingfrom 0.13␮g/mLto0.75␮g/mLandlowervaluesofMIC50andMIC90(0.38␮g/mLand0.5␮g/mL).

Incontrast,vancomycinandlinezolidhadhigherMICvalues,whichrangedfrom0.5␮g/mL to2.0␮g/mLandfrom0.38␮g/mLto4.0␮g/mL,respectively.TedizolidMICswere2-to5-fold lowerthanthoseoflinezolid.Clinicalcharacteristicsshowedhighpreviousantimicrobial useandhospitalizationhistory.ThemajorityofthestrainsbelongtotheCC8harboringthe SCCmecIVcandwereassociatedwiththespat1610(29.33%,n=44).

Conclusion: Invitroeffectivenessoftedizolidwassuperiorforisolatesfromskinandsoft tissueinfectionsincomparisonwiththeotherantibioticsevaluated.Theaboveaddedtoits lesstoxicity,goodbioavailability,dailydoseandunnecessityofdosageadjustment,make tedizolidinapromisingalternativeforthetreatmentofinfectionscausedbyMRSA.

∗ _{Corresponding}_author.

E-mailaddress:jnatalia.jimenez@udea.edu.co(J.N.JiménezQuiceno). http://dx.doi.org/10.1016/j.bjid.2017.03.010

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Introduction

Staphylococcusaureusisoneofthemostimportantpathogens inhumans,beingresponsableforvarioustypesofinfections inthehealthcareandcommunitysettings.1,2_Among_of_these, skinandsofttissueinfections(SSTIs)playanimportantrole, notonlybytheirhighfrequencybutalsoduetosevereforms thataffectdeeptissues,causingseriousimplicationsashigh morbidityratesandincreasedhospitalstayandcosts.1,3

Thismicroorganismischaracterizedbyitshighcapacityto adapttoantimicrobialsbytheacquisitionofseveralresistance mechanisms.2–4 _{Particularly,} _the _emergence _of methicillin-resistanceisolates (MRSA) haslimited therapeuticoptions, becausethisresistanceinvolveslowafﬁnityforall␤-lactam antibiotics.5

Vancomycinhasbeenconsidered aneffectiveoptionfor the treatment ofskinand softtissue infections caused by MRSA.However,thehighburdenoftheseinfectionsin hos-pitalshasledtooveruseofthisantibioticwhichinturnhas ledtoincreasedvaluesofminimuminhibitoryconcentration (MIC),emergenceofintermediateandtotalresistancetothis antimicrobialandincreasedmortality.6–8

Thissituationunderscorestheneedfornewantimicrobial optionstothetreatmentofinfectionscausedbyMRSAwhich respondtochangingresistancepatterns.8_Currently,_the ther-apeuticoptionsapprovedbyFoodandDrugAdministration (FDA)fortheSSTIsbyMRSAincludedaptomycin,linezolid, andtherecentlyintroduced,tedizolid.9,10

Tedizolid is a novel oxazolidinone with high potential of action that is approximately four times more potent than linezolid.9,10 _Although _the _mechanism _of _action _is similar toother oxazolidinones, tedizolid has shown more advantages,asloweradverseeffectsovershortcoursesof ther-apyandfavorablepharmacokinetics.9–11 _Tedizolid_shows_an increasedactivityagainstspeciesofstaphylococciand entero-cocci,includingdrug-resistant MRSAand vancomycin-and linezolid-resistantphenotypes.9–11

Constantchangesintheepidemiologyofinfectionscaused byS.aureusreafﬁrmthatthismicroorganismisamajorthreat forpublichealthandhighlightstheneedtoevaluate thera-peuticalternativesthatallowforabetterprognosisofthese infections.

In Colombia, MRSA (both healthcare-associated and community-associated) has become a worrisome clinical problem,withageneralfrequencyof27%,reachinginsome citiesupto50%.12_This_situation_brings_about_new_challenges forthetreatmentofthisinfectionsandpatientsafety.

Therefore,theaimofthisstudywastodetermineinvitro

susceptibilitytovancomycin,daptomycin,linezolidand tedi-zolidofMRSAclinicalisolatesfrompatientswithskinandsoft tissueinfections,collectedinthreetertiary-carehospitalsof Medellin,Colombia.

Material

and

methods

Bacterialisolates

Methicillin-resistantS.aureusisolateswerecollectedinthree tertiary-carehospitalsofMedellin,Colombia,fromFebruary

2008 to June 2010, as part of a previous cross-sectional study.13–15_Hospitals_A_and_B_are_hospitals_with_high_level_of complexitywith754and286beds,respectively,whichprovide servicesinallmedicalspecialties;whereashospitalCisa 140-bedcardiologyhospital.

Clinicalandepidemiologicalinformation

Clinicalandepidemiologicaldatawereobtainedfrommedical records.Informationincludeddemographicaspects,medical history,comorbidities,lengthofhospitalstayandoutcomesat discharge.Infectionswereclassiﬁedascommunity-associated (CA-MRSA)orhealthcare-associated(HA-MRSA),accordingto deﬁnitionsestablishedbytheCDC.16

TheresearchprotocolwasapprovedbytheBioethics Com-mittee for human Research at Universidad de Antioquia (CBEIHSIU-approvalNo.0841150).

Strainsandantibioticsusceptibility

The identiﬁcation ofS. aureus was conducted by standard laboratory methods based on colony morphology insheep blood agar and phenotyping methods such as catalase and coagulase. Antibiotic susceptibilities of S. aureus

isolates were assessed in accordance with Clinical Lab-oratory Standards Institute guidelines (CLSI, 2009) using a VITEK-2® instrument (bioMérieux Lyon, France). The Antibiotics evaluated included clindamycin, erythromycin, gentamicin, linezolid, moxiﬂoxacin, oxacillin, rifampin, tetracycline,tigecycline,trimethoprim-sulfamethoxazoleand vancomycin.

EvaluationofthesusceptibilitythroughEpsilometertest

The MICs to vancomycin, daptomycin, linezolid and tedi-zolid were determined using the Epsilometer test method (E-test)accordingtothemanufacturer’sinstructions(Etest® bioMérieuxandLiofilchem®MICTestStrip).MIC50andMIC90, thatcorrespondrespectivelytothe50%andthe90%ofstrains inhibitedbyaspecificconcentrationofeachantibioticwere obtained. TheMIC breakpoints were determined according to the criteria defined by CLSI, 2016 as follows: for van-comycin, values less than or equal to 2␮g/ml, between 4 and8␮g/ml,orgreaterthanorequalto16␮g/mlwere con-sideredsusceptible,intermediateandresistant,respectively; for daptomycin, these values were less than or equal to 1␮g/mlforsusceptibilityandhighervaluesweredeemedas non-susceptible; for linezolid, valuesless than or equalto 4␮g/mlweredeemedsusceptibleandgreaterthan orequal to 8␮g/ml resistant; finally, for tedizolid, values less than or equal to 0.5␮g/ml were considered susceptible, 1␮g/ml intermediateandvalueshigherthanorequalto2␮g/ml resis-tant. Strain ATCC 29213ofS. aureuswasused asacontrol strain.

Molecularcharacterization

Presenceofthespecies-speciﬁcnucandfemAgenes,aswell asthemecAgene(determinantofmethicillinresistance)were veriﬁed by polymerase chain reaction (PCR) as previously

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Table1–ClinicalandepidemiologicalcharacteristicsamongMRSAinfections.

Characteristics Total CA-MRSA HA-MRSA p-Value

No(%) No(%) No(%)

Hospital 0.077

HospitalA 91(60.67) 57(54.81) 34(73.91)

HospitalB 56(37.33) 45(43.27) 11(23.91)

HospitalC 3(2.00) 2(1.92) 1(2.17)

YearofMRSAisolation

2008 61(40.67) 44(42.31) 17(36.96) 0.825 2009 64(42.67) 43(41.35) 21(45.65) 2010 25(16.67) 17(16.35) 8(17.39) Gender 0.938 Male 92(61.33) 64(61.54) 28(60.87) Female 58(38.67) 40(38.46) 18(39.13) Age(years) Median(RIQ) 48(29–64) 48.5(31.5–65.0) 42(25–57) 0.110

Hospitalstay(days)

Median(RIQ) 19(9–36) 16(8–34) 28(17–48) 0.003 Comorbidities 128(85.33) 89(85.58) 39(84.78) 0.899 Diabetesmellitus 49(32.67) 36(34.62) 13(28.26) 0.444 Atopy 7(4.67) 3(2.88) 4(8.70) 0.120 Neoplasia 13(8.67) 10(9.62) 3(6.52) 0.535 Immunosuppression 25(16.67) 15(14.42) 10(21.74) 0.268

Chronicrenaldisease 21(14.0) 18(17.31) 3(6.52) 0.079

Traumainpast6months 39(26.0) 25(24.04) 14(30.43) 0.410

Historyinthepastyearof:

Hospitalization 84(56.00) 66(63.46) 18(39.13) 0.006

Surgery 46(30.67) 33(31.73) 13(28.26) 0.671

Dialysis 7(4.67) 6(5.77) 1(2.17) 0.336

StayinICU 6(4.0) 3(2.88) 3(6.0) 0.295

Stayinburnsunit 2(1.33) 1(0.96) 1(2.17) 0.551

Stayinthepastyearinhomenursing 5(3.33) 4(3.85) 1(2.17) 0.599 Antimicrobialuseinpast6months 73(51.41) 49(50.52) 24(53.33) 0.755

Invasivemedicaldevices 58(38.67) 40(38.46) 18(39.13) 0.938

Centralvenouscatheter 13(8.67) 9(8.65) 4(8.70) 0.993

Probes 26(17.33) 16(15.38) 10(21.74) 0.343

Osteosynthesismaterial 15(16.0) 10(9.62) 5(10.87) 0.813

Outcome 0.010

Cure 139(92.67) 100(97.09) 39(86.67)

Death 9(6.0) 3(2.91) 6(13.33)

described.17,18 _Genes _encoding _{staphylococcal} _enterotoxins (sea,seb,sec,sed,see),toxicshocksyndrometoxin1(tst),and exfoliative toxins A and B(eta, etb) were detectedby mul-tiplexPCR. ThelukS/F-PVgenesencoding Panton-Valentine leukocidin(PVL),aswellasthearcAgenefromthe USA300-associatedargininecatabolic mobile element (ACME), were alsoassayed.18,19_Strain_typing_was_performed_using_protein_A typing(spa),multilocussequencetyping(MLST),andSCCmec typing.20–23

Statisticalanalyses

Comparisons of clinical characteristics were carried out between CA-MRSA- and HA-MRSA-infected patients after applyingCDC criteria.Categoricalvariables were compared usingchi-squaretestorFisher’sexacttestandMann–Whitney

Utests for continuous variables. p-Values≤0.05 were con-sidered statistically signiﬁcant. Statistical analyses were performedusingthesoftwarepackageStata®v14.0.

Results

Atotalof150MRSAisolatesfromadultpatientswithskinand softtissueinfections wereevaluated.Thedemographicand clinicalcharacteristicsofpatientsaresummarizedinTable1. Themajorityofpatientsweremale(61.33%,n=92),withanage rangebetween15and89yearsoldandhospitalizedinhospital A(60.67%,n=91).

Above 69% of infections were classiﬁed as community-associatedaccordingtoCDCcriteriaafterindividual assess-ment ofcases;the medicalhistories revealed frequentuse ofantibiotics(51.41%,n=73),comorbiditiesmainlydiabetes mellitus (32.67%, n=49), and history in the past year of hospitalization and surgery (56%, n=84 and 30.67%, n=46, respectively).Themostfrequentoutcomewascure(92.67%,

n=139).

When comparing clinical characteristics among MRSA infections(CA-MRSAandHA-MRSA),threevariablesshowed statistically signiﬁcant differences:hospital stay (p=0.003),

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Table2–SCCmectypesamongtoCA-MRSAand HA-MRSAisolates.

SCCmec type

Total CA-MRSA HA-MRSA

No(%) No(%) No(%) SCCmecI 43(0.67) 21(20.19) 22(47.83) SCCmecII 1(28.67) 1(0.96) 0 SCCmecIII 0(0.67) 0 0 SCCmecIV 5(3.33) 3(2.88) 2(4.35) SCCmecIVa 5(3.33) 5(4.81) 0 SCCmecIVc 95(63.33) 73(70.19) 22(47.83) Nontypable 1(0.67) 1(0.96) 0

history of hospitalization (p=0.06) and outcome (p=0.010). LengthofhospitalstaywaslongerforpatientswithHA-MRSA infections,whileprevious hospitalizationhad amajor ten-dencyamongCA-MRSAinfections.Theoutcomedeathwas morefrequentamongHA-MRSAgroup.

Molecularcharacterizationofisolates

Thepresenceofnuc,femAandmecAgeneswereconﬁrmed inall isolates.Themostcommonclonalcomplex wasCC8 (63.3%,n=95), followedbyCC5 (31.3%,n=47). Furthermore, CC45(1.3%),CC1(0.7%)andCC30(0.7%)weredetectedinlow frequency.

Regardingtypingofchromosomecassettemec(SCCmec),a highpercentofisolatesclassiﬁedasCA-MRSAandHA-MRSA harboredSCCmectypeIVc(n=73,70.19%andn=22,47.83%, respectively),followed bySCCmec typeI(n=21,20.19%and

n=22,47.83%,respectively).TheremainingSCCmectypeswere presentatverylowfrequency(Table2).

Typingofchromosomecassettemecaccordingtotedizolid MICshowedthatthemostcommonwastheSCCmectypeIVc (63.3%,n=95)forallisolates,independentlytotedizolidMIC, followedbytheSCCmectypeI(28.7%,n=43)(Fig.1).

SeveraltypesoftheproteinAwerefound:t1610(30.67%,

n=46),t149(16.67%,n=25),t008(11.33%,n=17),andothersas t024(10%,n=15),t1311(4%,n=6)andt7279(4%,n=6).

ThestrainscarryingtheSCCmectypeIbelongedtothespa

t149andCC5.WhilethestrainscarryingSCCmecIVcbelonged tospatypest1610,t008,andt024oftheCC8.

CC8MRSAstrainsharboringSCCmectypeIVcandbelonged to the spa t1610 were more frequent (29.33%, n=44) and

0 10 20 30 40 50 60 0.75 0.5 0.38 0.25 0.19 0.13 No . of is ol at e s MIC SCCmecIVc SCCmecI

Fig.1–SCCmectypesaccordingtotedizolidMICvaluesin MRSAisolates.

presentedMICsvaluesfortedizolidbetween0.38␮g/mLand 0.50␮g/mL.

Regarding to virulence factors,the most common gene waslukS/F-PV(85.8%,n=97),followedbyenterotoxinB(18.6%,

n=21),toxicshocksyndrometoxin(17.7%,n=20)and entero-toxinD(8.8%,n=10)genes.EnterotoxinA,CandEwerefound inonlythreeisolates(0.9%).

Antimicrobialsusceptibility

AmongthetotalofMRSAisolates,43.33%(n=65)and35.33% (n=53) were resistant to tetracycline and erythromycin, respectively. Resistance to clindamycin, gentamicin, moxi-ﬂoxacinandrifampin,waslessthan21%.

TheMICvaluesobtainedthroughE-testshowed suscep-tibility tovancomycin, daptomycin,linezolidand tedizolid, except for one isolate with MIC=1.5␮g/mL to daptomycin (Table3).Tedizolidwasmoreactivethanotherantimicrobials, withMICvaluesrangingfrom0.13␮g/mLto0.75␮g/mL,and lowervaluesofMIC50andMIC90(0.38and0.5,respectively).In contrast,vancomycinandlinezolidhadhighMICswithvalues evenabove1.5␮g/mL(Table3,Fig.2).

MostisolatesshowedatedizolidMICof0.38␮g/mL(38%,

n=57)andalinezolidMICof2␮g/mL(36%,n=55). Interest-ingly, 18.7%(n=28)and 2%(n=3) oftheisolates,presented MICsvaluesof3␮g/mLand4␮g/mLtolinezolid,respectively. Additionally,tedizolidMICsvalueswere3-to5-foldlowerthan thoseoflinezolid(Fig.2).

The MICs values for the S. aureus ATCC 29213 control strain,fallingwithintherangeforthequalitycontrol recom-mended byCLSI(0.5–2␮g/mLforvancomycin,0.12–1␮g/mL fordaptomycin,0.5–2␮g/mLforlinezolid,and0.25–1␮g/mL fortedizolid).

Discussion

TedizolidhasbeenrecentlyapprovedbytheFDAfortreatment of skinand soft tissueinfections causedby Gram-positive bacteria, includingMRSA.11_The_importance_of_this antimi-crobial is focusedon the emergence ofless susceptible or resistantMRSAstrainstovancomycin(hVISAandVISA)and thediscoveryofapossibledisseminationofcfrgene,thatis horizontallytransferableandconfersresistancetolinezolid.24 Theresultsofthisstudyevidencedthattedizolidwasthe most effective antibiotic compared withvancomycin, dap-tomycin and linezolid,showinglower MIC valuesalthough its resistance breakpoint is considerably lower than the other antimicrobialsandbeingconsistentwithconclusions inotherstudies.25_This_can_be_better_appreciated_with_MIC

50 and MIC90 values, that points to the effectiveness of the antibiotic and the behavior of susceptibility of MRSA iso-lates.MIC90displayimportantdifferencesbetweenthefour antibioticstested.Tedizolidwasnotablysuperior,withMIC90 valuesbelow0.5␮g/mL,whiletheMIC90valueswere1␮g/mL, 1.5␮g/mL,and3␮g/mLfordaptomycin,vancomycinand line-zolid,respectively.

Greater activity and a narrow range of tedizolid MICs (between 0.19 and 0.75␮g/mL) has been reported in sev-eral studiesacrossavarietyofcultureconditionsandwith

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Table3–FrequencyofoccurrenceandcumulativepercentdistributionofMICsforselecteddrugsagainstS.aureus isolates.

Antimicrobials No.(cumulative%)ofisolatesinhibitedatMIC(␮g/ml)of: MIC50 MIC90 %Susceptible %Resistant

≤0.19 0.25 0.38 0.5 0.75 1 1.5 2 3 4 >4 Daptomycin0(0) 3(2.0) 31(22.7) 46(53.4) 46(84.1) 23(99.4) 1(100) 0 0 0 0 0.5 1 100 0 Vancomycin0(0) 0(0) 0(0) 5(3.3) 30(23.3) 76(74.0) 36(98.0) 3(100) 0 0 0 1 1.5 100 0 Linezolid 0(0) 0(0) 1(0.7) 1(1.4) 5(4.7) 18(16.7) 39(42.7) 55(79.4) 28(98.1) 3(100) 0 2 3 100 0 Tedizolid 12(8)34(30.7) 57(68.7) 41(96) 6(100) 0 0 0 0 0 0 0.38 0.5 100 0 1% 9% 23% 37% 27% 4% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 4.0 3.0 2.0 1.5 1.0 0.75 0.5 0.38 0.25 0.19 0.13 % of isolates MIC Tedizolid 2% 21% 31% 31% 15% 1% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 4.0 3.0 2.0 1.5 1 0.75 0.5 0.38 0.25 0.19 0.13 % of isolates MIC Daptomycin 3% 20% 24% 2% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 4.0 3.0 2.0 1.5 1.0 0.75 0.5 0.38 0.25 0.19 0.13 % of isolates MIC Vancomycin 1% 1% 3% 12% 26% 37% 19% 2% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 4.0 3.0 2.0 1.5 1.0 0.75 0.50 0.38 0.25 0.19 0.13 % of isolates MIC Linezolid 51%

Fig.2–Comparisonbetweentedizolid,daptomycin, vancomycinandlinezolidMICinMRSAisolates.

reference and clinical isolates of S. aureus.26 _A _study car-ried out in South Korea reported a tedizolid MIC90 of 0.5␮g/mLin Gram-positive isolates as MRSA, vancomycin-resistantenterococci,S.pneumoniae,S.pyogenes,S.agalactiae

and Clostridium spp.and showedmorepotencyoftedizolid than linezolidorvancomycin.27_Similarly,_a_survey_study_of 1063Gram-positiveandGram-negativeisolatesfromUnited States,GreatBritain,France,Germany,andAustraliarevealed thattedizolidwas4–8foldmorepotentagainststaphylococci thanlinezolid,withaMIC90of0.5␮g/mL,and2–8foldmore potent than vancomycin against these microorganisms.28 More recent studies have conﬁrmed these results, which have shown tedizolid MICs 4–32 fold lower than those of linezolid in clinical isolatesof linezolid-resistant staphylo-cocciandenterococci,29_maintaining_activity_against_isolates withreducedsusceptibilitytoalternativeagentssuchas van-comycinanddaptomycin.25,30,31

Tedizolidandlinezolidarebothoxazolidinonesandshare many characteristicssuchasactivityagainstGram-positive bacteria,thesamemechanismofactionandhighoral bioavail-ability.However,tedizolid hasshownbetterinvitroactivity compared to linezolid, asit can bind to additional targets sitesin23srRNAwhichleadstoactivityagainstMRSAstrains with linezolid resistancemediated bycfr gene mutation.32 Additionally, tedizolid is approximately 90% protein-bound andhasahalf-lifeneartwo-foldgreaterthanlinezolid, lead-ing toonlysixdaysoftherapy(tedizolid200mgoncedaily forsixdaysvslinezolid600mgtwicedailyfor10days)and notrequiringdosageadjustmentinpatientswithanyrenal or hepatic dysfunction.33–35 _Furthermore, _the _toxicity _and

in vitro tedizolid resistance rates are lower than for other antimicrobials.36,37

Inpresentstudy,highMICsvalueswereobservedfor van-comycinanddaptomycin,beingbeyondorintheupperlimit ofsusceptibility.Mostcliniciansusevancomycinforempiric anddeﬁnitivetherapyforMRSAinfections;however,recent reportshavedrawnattentiontoincreasedtreatmentfailures atMIC1␮g/mL,althoughCLSIbreakpointdeﬁnestheupper limitofsusceptibilityin2␮g/mL.8_Besides,_clinical_outcomes withvancomycindependofbacterialloadatsiteofinfection, andhigherratesofnephrotoxicityareassociatedwith high-dosetherapy.38

Daptomycinisanalternativetovancomycin forpatients withMRSAinfections,butsomeauthorshaverecommended tousehighdosestominimizetheemergenceofelevatedMIC values,whichhasbeenassociatedwithanincreaseinthe van-comycinMICandtheheteroresistantphenotype(hVISA).39,40 Interestingly, in this study the activity of tedizolid was maintained instrainsisolated from patients withdifferent characteristics including an age range between 15 and 89 yearsold,differentcomorbiditiesandpreviousantimicrobial

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use.Likewise,theMICvaluesfortedizolidwassimilarinall isolatesandtheresultswereconsistentinbothcommunity andhealthcare-associatedinfections.

On the other hand, the most frequent genotype was CC8-t1610-SCCmecIVc, which is common in community-associatedstrainswithPanton-Valentineleucocidin,against which tedizolid retained activity, too.41 _These community-associatedstrainsarebeingintroducedtohospitals,replacing healthcare-associatedstrains,accordingtopreviousstudies fromMedellín.42

Efﬁcacy, safety, and tolerability of tedizolid have been evaluated in Latino patients and tedizolid had presented comparableefﬁcacy tolinezolid, sustained clinical success rates,andlowerabnormalplateletcountsand gastrointesti-nalevents,withoutwarrantingdoseadjustment.43_Countries likeColombia,whereMRSAhasbecomeaworrisomeclinical problem,withageneralfrequencyof27%,reachingupto50% insomecities,12_increased_resistance_rates_and_high_antibiotic pressuregenerateadditionalcosttohealthsystem. Therapeu-ticalternatives liketedizolidarethusnecessarytoimprove prognosisofinfectionscausedbyGram-positivebacteriasuch asS.aureus.44

Inconclusion,invitroeffectivenessoftedizolidwas supe-rior for isolates from skin and soft tissue infections in comparisonwithothertherapyalternativeslikevancomycin, daptomycinandevenlinezolid.Thecombinationofless tox-icity, goodbioavailability, oncedailydose and norequiring dosageadjustmentmakestedizolidapromisingalternative forthetreatmentofinfectionscausedbyS.aureus,including methicillin-resistantisolates.

Funding

ThisworkwassupportedbyBAYERS.A.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

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