DrugTreatmentofCommonSTDs:PartI.

Herpes,Syphilis,
Urethritis,ChlamydiaandGonorrhea

CAROLWOODWARD,PHARM.D.,WestVirginiaUniversityHospitals,Morgantown,WestVirginia
MELANIEA.FISHER,M.D.,M.SC.,WestVirginiaUniversity,Morgantown,WestVirginia
AmFamPhysician.1999Oct160(5):13871394.

ThisisPartIofatwopartarticleondrugtreatmentofcommonsexuallytransmitteddiseases.PartII,VaginalInfections,PelvicInflammatoryDiseaseand
GenitalWarts,(http://www.aafp.org/afp/1999/1015/p1716.html)willappearinthenextissueofAFP.

RelatedEditorial(http://www.aafp.org/afp/1999/1001/p1335)

In1998,theCentersforDiseaseControlandPreventionreleasedguidelinesforthetreatmentofsexuallytransmitteddiseases.Severaltreatment
advanceshavebeenmadesincethepreviousguidelineswerepublished.PartIofthistwopartarticledescribescurrentrecommendationsforthe
treatmentofgenitalulcerdiseases,urethritisandcervicitis.Treatmentadvancesincludeeffectivesingledoseregimensformanysexuallytransmitted
diseasesandimprovedtherapiesforherpesinfections.Twosingledoseregimens,1goforalazithromycinand250mgofintramuscularceftriaxone,
areeffectiveforthetreatmentofchancroid.Athreedaycourseof500mgoforalciprofloxacintwicedailymaybeusedtotreatchancroidinpatients
whoarenotpregnant.Parenteralpenicillincontinuestobethedrugofchoicefortreatmentofallstagesofsyphilis.Threeantiviralmedicationshave
beenshowntoprovideclinicalbenefitinthetreatmentofgenitalherpes:acyclovir,valacyclovirandfamciclovir.Valacyclovirandfamciclovirarenot
yetrecommendedforuseduringpregnancy.Azithromycininasingleoral1gdoseisnowarecommendedregimenforthetreatmentofnongonococcal
urethritis.

Severaladvanceshavebeenmadeinthetreatmentofsexuallytransmitteddiseases(STDs).Theseadvanceshavebeenincorporatedintothe1998Guidelinesfor
theTreatmentofSexuallyTransmittedDiseases,publishedbytheCentersforDiseaseControlandPrevention(CDC).1

HighlyeffectivesingledoseoraltherapiesarenowavailableformostcommoncurableSTDs.Singledoseregimensmaybeusedforthetreatmentofchancroid,
nongonococcalurethritis,uncomplicatedgonococcalinfections,bacterialvaginosis,trichomoniasis,candidalvaginitisandchlamydialinfections.

Improvedtherapiesarenowavailableforthetreatmentofgenitalherpesandhumanpapillomavirus(HPV)infections.Newregimenshavebeenapprovedforthe
useofacyclovir(Zovirax)inthetreatmentofgenitalherpes.Inaddition,twonewantiviralagents,valacyclovir(Valtrex)andfamciclovir(Famvir),havebeenlabeled
forthetreatmentofgenitalherpes.PatientappliedtherapiesarenowrecommendedformanagementofHPV.

Anewtestingmethodforthediagnosisofchlamydialinfectionsemploysanextremelyaccurateurinetestthatcaneasilybeincorporatedintoscreeningprograms.
HepatitisAandhepatitisBvaccinesarenowrecommendedforallsexuallyactiveadolescentsandyoungadults.

TreatmentsforSTDsinpregnantwomenhavebeenimproved,producingfewersideeffectsandreducingthenumberofprematurebirths.Treatmentguidelinesfor
themanagementofSTDsinspecialpatientpopulations,includingpregnantwomen,wererecentlypublishedinthisjournal.2

GenitalUlcerDiseases
Beforeagenitalulceristreated,anaccuratediagnosiswithappropriatetestingisessential.Concomitanttestingforhumanimmunodeficiencyvirus(HIV)infection
shouldbeconsidered.

CHANCROID
Thegoalsoftherapyforchancroidaretocuretheinfection,resolvesymptomsandpreventtransmission.Fourrecommendeddrugregimensforthetreatmentof
chancroidareshowninTable1.Twoaresingledoseregimensconsistingofeitherazithromycin(Zithromax)orceftriaxone(Rocephin).Erythromycin,which
continuestoberecommendedforthetreatmentofchancroid,requiresasevendaydosingregimen.Ciprofloxacin(Cipro)hasbeenaddedtotheguidelinesforthe
treatmentofchancroid.However,ciprofloxaciniscontraindicatedforuseinpregnantandlactatingwomen,andinpatientsunder18yearsofage.Allfourregimens
areeffectivefortreatmentofchancroidinpatientswithorwithoutHIV.Ofnote,severalisolatesofchancroidwithintermediateresistancetoeitherciprofloxacinor
erythromycinhavebeenreported.Patientsshouldbereexaminedwithinthreetosevendaysafterinitiationoftherapy.Symptomaticimprovementshouldbe
reportedwithinthreedaysiftreatmentissuccessful.

View/PrintTable

TABLE1
TreatmentofDiseasesCharacterizedbyGenitalUlcers
REGIMENS

DISEASE REGIMENS
AGENT DOSAGE COST*

DISEASE AGENT DOSAGE COST*

Chancroid Azithromycin(Zithromax) 1gorallyinasingledose $20.50(brand)

Ceftriaxone(Rocephin) 250mgIMinasingledose 13.00(brand)

Ciprofloxacin(Cipro) 500mgorallytwicedailyfor3days 24.00(brand)

Erythromycinbase 500mgorallyfourtimesdailyfor7days 6.50to9.00(generic)

Granulomainguinale

Recommendedregimen Trimethoprim/sulfamethoxazole Doublestrength,takenorallytwicedailyfor21days 54.00(brand)14.00to

(Bactrim,Septra) 25.00(generic)

or

Doxycycline(Vibramycin) 100mgorallytwicedailyfor21days 167.00(brand)

Alternativeregimen Ciprofloxacin 750mgorallytwicedailyfor21days 168.00(brand)

or

Erythromycinbaseplus(during 500mgorallyfourtimesdailyfor21days 19.50to27.00(generic)

pregnancy)

Aminoglycoside(i.e., 1mgperkgIVthreetimesdailyfor21days 337.00(brand)66.00to

gentamicin) 312.00(generic)

Lymphogranulomavenereum

Recommendedregimen Doxycycline 100mgorallytwicedailyfor21days 80.00(brand)5.50to

26.50(generic)

Alternativeregimen Erythromycinbase 500mgorallyfourtimesdailyfor21days 42.00(brand)20.50to

(includingpregnancy) 27.50(generic)

Herpessimplexvirus

Firstepisode Acyclovir(Zovirax) 400mgorallythreetimesdailyfor7to10days 53.00(brand)37.50to

43.00(generic)

or

200mgorallyfivetimesdailyfor7to10days 45.00(brand)32.00to
37.00(generic)

Famciclovir(Famvir) 250mgorallythreetimesdailyfor7to10days 70.00(brand)

Valacyclovir(Valtrex) 1gorallytwicedailyfor7to10days 56.00(brand)

Recurrentepisodes Acyclovir 400mgorallythreetimesdailyfor5days 38.00(brand)27.00to

31.00(generic)

or

200mgorallyfivetimesdailyfor5days 32.50(brand)23.00to
26.50(generic)

or

800mgorallytwicedailyfor5days 50.00(brand)35.00to
40.00(generic)

Famciclovir 125mgorallytwicedailyfor5days 28.00(brand)

Valacyclovir 500mgorallytwicedailyfor5days 31.00(brand)

Dailysuppressivetherapy Acyclovir 400mgorallytwicedaily 5.00(brand)3.50to4.00

(generic)

Famciclovir 250mgorallytwicedaily 6.50(brand)

 REGIMENS

DISEASE AGENT DOSAGE COST*

Valacyclovir 500mgorallyoncedaily(inpatientswith<10episodesperyear) 3.00(brand)

Valacyclovir 1,000mgorallyoncedaily(inpatientswith>10episodesperyear) 6.00(brand)

Syphilis

Primaryandsecondary BenzathinepenicillinG 2.4millionunitsIMinasingledose 24.00(brand)

disease

Penicillinallergy Doxycycline 100mgorallytwicedailyfor14days 111.00(brand)6.00to

25.00(generic)

Tetracycline 500mgorallyfourtimesdailyfor14days 3.50to6.00(generic)

Earlylatentdisease BenzathinepenicillinG 2.4millionunitsIMinasingledose 24.00(brand)

Latelatent,unknown BenzathinepenicillinG 7.2millionunitsIMtotal,dividedintothreeweeklydosesof2.4 71.50(brand)

duration,tertiarydisease millionunitseach

Neurosyphilis AqueouscrystallinepenicillinG 18to24millionunitsIVdaily,dividedas3to4millionunitsevery4 12.00(generic)

hoursfor10to14days

Procainepenicillinplus 2.4millionunitsofpenicillindaily,plus500mgprobenecidorallyfour 277.00(generic)

probenecid timesdaily,bothfor10to14days

IM=intramuscularlyIV=intravenously.

ReprintedfromCentersforDiseaseControlandPrevention.1998Guidelinesforthetreatmentofsexuallytransmitteddiseases.MMWRMorbMortalWklyRep199847(RR1):1111.

*Estimatedcosttothepharmacist(roundedtothenearesthalfdollar)basedonaveragewholesaleprices(forlowestdosagelevelandtreatmentperiod)inRedbook.Montvale,N.J.:
MedicalEconomicsData,1999.Costtothepatientwillbehigher,dependingonprescriptionfillingfee.

Costforonedayoftherapy.

GENITALHERPES
Genitalherpesisarecurrent,incurableviraldisease.Patientcounselingshouldincludeinformationaboutrecurrentepisodes,asymptomaticviralshedding,
perinataltransmissionandsexualtransmission.Episodicantiviraltherapyduringoutbreaksmayshortenthedurationofthelesions,andsuppressiveantiviral
therapymaypreventrecurrences.

Duringthefirstclinicalepisode,thegoalofsystemicantiviraldrugtherapyistocontrolthesignsandsymptomsofgenitalherpes.Dailysuppressivetherapyis
recommendedforuseinpatientswhohavesixormorerecurrencesperyear.Threeantiviralmedicationshavebeenprovedinrandomizedtrialstoprovideclinical
benefitinpatientswithgenitalherpes:acyclovir,valacyclovirandfamciclovir.Clinicalexperiencewithsystemicacyclovirinthetreatmentofgenitalherpeshasbeen
substantial.Topicaltherapyislesseffectivethansystemictherapy,anditsuseisnotrecommended.Twonewerantiviralagentsarevalacyclovirandfamciclovir.3,4
Valacyclovirisavalineesterofacyclovirwithenhancedabsorptionpropertieswhenadministeredorally.Famciclovir,aprodrugofpenciclovir,alsohashighoral
bioavailability.Thesafetyofantiviraltherapyinpregnantwomenhasnotbeenestablished,butextensiveclinicalexperiencewithacyclovirhasbeenreassuring.
Severeorfirstepisodediseasethatoccursduringpregnancymaybetreatedwithacyclovir.However,theroutineadministrationofantiviralagentsinpregnant
womenwithuncomplicatedorrecurrentgenitalherpesisnotrecommended.

SYPHILIS
SyphilisisasystemicdiseasecausedbythesexualtransmissionofTreponemapallidum.Itcanpresentasprimary,secondaryortertiarydisease.Primarydisease
presentswithoneormorepainlessulcersorchancresattheinoculationsite.Secondarydiseasemanifestationsincluderashandadenopathy.Cardiac,neurologic,
ophthalmic,auditoryorgummatouslesionscharacterizetertiaryinfections.Latentdiseasemaybedetectedbyserologictesting,withoutthepresenceofsignsand
symptoms.Earlylatentdiseaseisdefinedasdiseaseacquiredwithintheprecedingyear.Allothercasesoflatentsyphilisareconsideredlatelatentdiseaseor
diseaseofunknownduration.

Therecommendedtreatmentregimenshavenotchangedsincethe1993CDCGuidelines.ParenteralpenicillinGisstillthepreferreddrugfortreatingallstagesof
syphilis,includingdiseaseinpregnantwomen.Table1outlinesthedifferentpenicillinpreparationsandtheproperdosagesanddurationsoftherapy,dependingon
thestageofsyphilisatpatientpresentation.Patientswithearlydiseaseandpenicillinallergymaybedesensitizedfirstandthentreatedwithpenicillinortreatedwith
anotherrecommendedregimen.PatientswithHIVinfectionrequiretreatmentwithpenicillinatallstagesofsyphilis.TreatmentmaybeassociatedwiththeJarisch
Herxheimerreaction.Thisreactionisanacutefebrileillnessthatmayoccurwithinthefirst24hoursoftherapyandincludessymptomssuchasheadacheand
myalgias.Concomitantantipyretictherapymaybebeneficial.

GRANULOMAINGUINALEANDLYMPHOGRANULOMAVENEREUM
GranulomainguinaleandlymphogranulomavenereumarerareintheUnitedStates.Granulomainguinalepresentsasapainless,highlyvascularulcerthatis
causedbyCalymmatobacteriumgranulomatis.Patientswithlymphogranulomavenereumpresentmostoftenwithregionallymphadenopathyitisoftenadiagnosis
ofexclusion.ThediseaseiscausedbyLserogroupstrainsofChlamydiatrachomatis.Thediagnosisisusuallymadeclinicallyandserologically.Treatment
regimensforthesediseasesaregiveninTable1.

DiseasesCharacterizedbyUrethritisandCervicitis
URETHRITIS
Urethritisisaninfectioncharacterizedbymucopurulentorpurulentdischargeandburningduringurination.NeisseriagonorrhoeaeandC.trachomatisarethemost
commonbacterialpathogensassociatedwithurethritis.Empirictreatmentisrecommendedinhighriskpatientsandthoseunlikelytoreturnforfollowup.Treatment
guidelinesareoutlinedinTable2.

View/PrintTable

TABLE2
TreatmentofUrethritisandCervicitis*
REGIMENS

DISEASE AGENT DOSAGE COST

Nongonococcalurethritis

Recommendedregimens Azithromycin(Zithromax) 1gorally(singledose) $20.50(brand)

Doxycycline(Vibramycin) 100mgorallytwicedailyfor7days 55.50(brand)2.50to19.00

(generic)

Alternativeregimens Erythromycinbase 500mgorallyfourtimesdailyfor7 6.50to9.00(generic)

days

or

Erythromycinethylsuccinate 800mgorallyfourtimesdailyfor7 10.00to22.00(generic)

days

or

Ofloxacin(Floxin) 300mgorallytwicedailyfor7days 62.50(brand)

Ifhighdoseerythromycinisnot
tolerated:

Erythromycinbase 250mgorallyfourtimesdailyfor14 8.00to24.00(generic)

days

or

Erythromycinethylsuccinate 400mgorallyfourtimesdailyfor14 5.00to11.00(generic)

days

Recurrent/persistenturethritis

Metronidazole(Flagyl) 2gorallyinasingledose 11.50(brand)1.50to3.00

(generic)

pluseither

Erythromycinbase 500mgorallyfourtimesdailyfor7 6.50to9.00(generic)

days

or

Erythromycinethylsuccinate 800mgorallyfourtimesdailyfor7 10.00to22.00(generic)

days

Chlamydialinfection

Recommendedregimens Azithromycin 1gorally(singledose) 20.50(brand)

or

Doxycycline 100mgorallytwicedailyfor7days 55.50(brand)2.50to19.00

(generic)

Alternativeregimens Erythromycinbase 500mgorallyfourtimesdailyfor7 6.50to9.00(generic)

days

or

Erythromycinethylsuccinate 800mgorallyfourtimesdailyfor7 10.00to22.00(generic)

days
 REGIMENS

DISEASE AGENT DOSAGE COST

or

Ofloxacin 300mgorallytwicedailyfor7days 62.50(brand)

Gonococcalinfection

Uncomplicatedinfectionsofthecervix,urethraand Cefixime(Suprax) 400mgorallyinasingledose $7.50(brand)

rectum

or

Ceftriaxone(Rocephin) 125mgIMinasingledose 14.00per250mgvial(brand)

or

Ciprofloxacin(Cipro) 500mgorallyinasingledose 4.00(brand)

or

Ofloxacin 400mgorallyinasingledose 5.00(brand)

plus

Azithromycin 1gorallyinasingledose 20.50(brand)

or

Doxycycline 100mgorallytwicedailyfor7days 55.50(brand)2.50to19.00

(generic)

Uncomplicatedinfectionofthepharynx Ceftriaxone 125mgIMinasingledose 14.00per250mgvial(brand)

or

Ciprofloxacin 500mgorallyinasingledose 4.00(brand)

or

Ofloxacin 400mgorallyinasingledose 5.00(brand)

plus

Azithromycin 1gorallyinasingledose 20.50(brand)

or

Doxycycline 100mgorallytwicedailyfor7days 55.50(brand)2.50to19.00

(generic)

IM=intramuscularly.

ReprintedfromCentersforDiseaseControlandPrevention.1998Guidelinesforthetreatmentofsexuallytransmitteddiseases.MMWRMorbMortalWklyRep199847(RR1):1111.

*Mucopurulentcervicitisshouldbetreatedaccordingtotheguidelinesforchlamydialandgonococcalinfections.

Estimatedcosttothepharmacist(roundedtothenearesthalfdollar)basedonaveragewholesaleprices(forlowestdosagelevelsandtreatmentperiods)inRedbook.Montvale,
N.J.:MedicalEconomicsData,1999.Costtothepatientwillbehigher,dependingonprescriptionfillingfee.

SeveralregimensforthemanagementofpatientswithnongonococcalurethritisareoutlinedinTable2.Oralazithromycinisrecommendedassingledose
therapy.57Improvedcomplianceandtheabilitytoobservetherapyareadvantagesassociatedwithsingledoseregimens.

MUCOPURULENTCERVICITIS
Mucopurulentcervicitisisoftenasymptomatic.Itmaybedetectedbythepresenceofpurulentormucopurulentendocervicalexudate.Somewomenwiththis
conditionhaveanabnormalvaginaldischargeandreportvaginalbleedingaftersexualintercourse.C.trachomatisorN.gonorrhoeaeusuallycausemucopurulent
cervicitis,butinmanycasesneitherorganismcanbeisolated.PatientswithpositiveculturesornucleicacidamplificationtestsforthepresenceofC.trachomatisor
N.gonorrhoeaealwaysrequiretreatment.Empirictherapyisrecommendedwhenthelikelihoodofinfectionwitheitherorganismishighorwhenpatientsare
unlikelytoreturnfortreatment.RecommendedtreatmentregimensareoutlinedinTable2.

UncomplicatedChlamydialandGonoccocalInfections
CHLAMYDIALINFECTION
Chlamydialgenitalinfectionsarecommonamongadolescentsandyoungadultswhoaresexuallyactive.C.trachomatisinfectionmaybeassociatedwithpelvic
inflammatorydisease(PID),ectopicpregnancyandinfertility.Sincechlamydialinfectionisoftenasymptomaticandthesequelaecanbeserious,routinescreening
fordiseaseduringannualexaminationsisrecommended.Singledosetherapywithazithromycinisaseffectiveasasevendaycourseofdoxycycline(Vibramycin).
Doxycyclineislessexpensive,butazithromycinmaybecostbeneficialbecauseitprovidessingledose,directlyobservedtherapy.Erythromycinandofloxacin
(Floxin)alsomaybeusedtotreatC.trachomatis.Erythromycinislessefficaciousthanazithromycinanddoxycycline,anditsadversegastrointestinaleffectsmay
decreasepatientcompliance.Ofloxacinisaseffectiveastherecommendedregimensbutoffersnodosingorcostadvantages.Doxycyclineandofloxacinare
contraindicatedinpregnantwomen.Inaddition,thesafetyandefficacyofazithromycininpregnantwomenhasnotbeenestablishedtherefore,asevendaycourse
ofeithererythromycinoramoxicillinisrecommendedinthisgroup.Sinceneitherregimenisconsideredhighlyeffective,culturesshouldberepeatedinthreeweeks.

GONOCOCCALINFECTION
Menwithagonococcalinfectionexperiencesymptomsthatrequiretreatment,butwomenoftenareasymptomaticuntilcomplicationsoftheinfection,suchasPID,
occur.Forthisreason,screeningisrecommendedinhighriskpatients.CoinfectionwithC.trachomatisoftenoccursinpatientswithgonococcalinfections.The
costofdoxycyclinetherapyforC.trachomatisislessexpensivethantestingfortheorganism,soempirictreatmentofcoinfectionisbecomingroutine.Also,dual
therapywithdoxycyclineandazithromycinmaydecreasethedevelopmentofantimicrobialresistantN.gonorrhoeae,becausemostgonococciaresusceptibleto
bothdrugs.QuinoloneresistantN.gonorrhoeaehasbeenreportedintheUnitedStatesandisbecomingmorewidespreadinAsia.Atthistime,fluoroquinolone
regimenscanbeusedwithconfidence,butcontinuedmonitoringofemergingresistancewillbeimportant.

Table2outlinestherapyforgonococcalinfections.Foursingledoseregimensarenowavailablefortreatmentofuncomplicatedgonococcalinfectionsofthecervix,
urethraandrectum.Theyincludecefixime(Suprax),ceftriaxone,ciprofloxacinandofloxacin.Cefixime,ciprofloxacinandofloxacinaregivenorally,whileceftriaxone
isadministeredintramuscularly.Gonococcalinfectionsofthepharynxaremoredifficulttoeradicatebut,withtheexceptionofcefixime,therecommendedtherapyis
thesameasforurogenitalandanorectalinfections,andshouldincludeconcomitanttreatmentforchlamydialinfection.

TheAuthors showallauthorinfo
CAROLWOODWARD,PHARM.D.,isassistantdirectorofpharmaceuticalservicesatWestVirginiaUniversityHospitalsandclinicalassistantprofessorattheWest
VirginiaUniversitySchoolofPharmacy,bothinMorgantown.Dr.WoodwardreceivedherdoctorofpharmacydegreefromtheUniversityofNorthCarolinaatChapel
Hill.ShecompletedaresidencyinpharmacyatWestVirginiaUniversityHospitals,Inc....

REFERENCES showallreferences
1.CentersforDiseaseControlandPrevention.1998guidelinesforthetreatmentofsexuallytransmitteddiseases.MMWRMorbMortalWklyRep.199847(RR
1):1111....

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