Latest CDC Guidelines on Treating Sexually Transmitted Diseases: Part 1, Bacterial Infections

June 1, 2006

Some sexually transmitteddiseases (STDs), such assyphilis and gonorrhea, arecenturies-old scourges; othershave attained clinicalsignificance only in recent years.Despite the availability of effectivetherapy for many of these diseases,they remain an important publichealth problem.

Some sexually transmitteddiseases (STDs), such assyphilis and gonorrhea, arecenturies-old scourges; othershave attained clinicalsignificance only in recent years.Despite the availability of effectivetherapy for many of these diseases,they remain an important publichealth problem.

By promptly treating patientswith curable STDs, you can break thechain of transmission. Recently releasedmanagement guidelines fromthe CDC, which update those publishedin 1998, review the latestweapons at your disposal.1 Includedare new alternative regimens forearly syphilis, scabies, bacterial vaginosis,and granuloma inguinale.

Because of the comprehensivenature of the CDC guidelines andtheir importance for primary careclinicians, CONSULTANT will presenta 3-part overview, beginning inthis issue with the management ofsexually transmitted bacterial infections.In future issues, the treatmentof viral (excluding HIV), fungal, andprotozoal infections will be discussed.

SYPHILISDiagnosis. Patients who havesyphilis may present with signs andsymptoms of primary infection (anulcer or chancre at the infection site[Figure 1]); secondary infection (includingrash [Figure 2], mucocutaneouslesions, and lymphadenopathy);or tertiary infection (such as cardiac,ophthalmic, or auditory abnormalitiesand gummatous lesions). Latent infectionsare detected by serologic testing.

Darkfield examination and directfluorescent antibody tests of lesionexudate or tissue can help you definitively diagnose early syphilis. A presumptivediagnosis can be made with2 types of serologic tests:

  • Nontreponemal (such as VDRL andrapid plasma reagin [RPR] tests).
  • Treponemal (eg, fluorescent treponemalantibody absorption and microhemagglutinationassay for antibodyto Treponema pallidum)

.

Results from only one test are insufficientfor diagnosis because falsepositivenontreponemal test resultsare occasionally caused by othermedical conditions. Nontreponemaltest antibody titers usually correlatewith disease activity, and resultsshould be reported quantitatively. In most patients, the nontreponemal testeventually becomes nonreactive aftertreatment; however, some patientsmaintain persistent low titers of nontreponemalantibodies (a serofastreaction).

Although most patients whohave reactive treponemal test resultscontinue to have reactive results forthe rest of their lives, about 15% to25% who are treated during the primarystage of syphilis may becomenonreactive after 2 to 3 years. Avoidusing treponemal test antibody titersto assess treatment response, becausethey correlate poorly with diseaseactivity.

Sequential serologic tests shouldbe performed by the same method,preferably by the same laboratory. Eitherthe VDRL or RPR test can beused, but quantitative results cannotbe directly compared, because RPRtiters are often slightly higher thanVDRL titers.

Test all patients who have syphilisfor HIV infection. Also bear in mindthat HIV-infected patients can have unusuallyhigh, unusually low, or fluctuatingtiters when tested for syphilis.

Treatment. For more than 50years, parenteral penicillin G hasbeen used effectively to achieve alocal cure (healing lesions and preventingsexual transmission) and toforestall late sequelae. Give a singledose of benzathine penicillin G (2.4million U IM) to adults who have primaryor secondary syphilis.

The Jarisch-Herxheimer reaction(an acute febrile reaction oftenaccompanied by headache, myalgia,and other symptoms) can occur within24 hours after therapy, usuallyamong patients with early syphilis.Antipyretics may be used; however, these agents have not been proved toprevent this reaction.

Alternative regimens for nonpregnantadults with penicillin allergyare doxycycline (100 mg PO bid for14 days) and tetracycline (500 mg POqid for 14 days). These regimenshave been used for many years. Limitedevidence suggests that ceftriaxone(1 g/d either IM or IV for 8 to10 days) or azithromycin (single 2-gdose PO) may be effective for treatingearly syphilis. Because the efficacyof these regimens is not welldocumented, close follow-up of patientswho receive ceftriaxone orazithromycin is recommended. Pregnantwomen with penicillin allergyshould be desensitized and treatedwith penicillin.

Follow-up. Reexamine patientsand order serologic testing at 6months and at 12 months. A sustained4-fold increase in the nontreponemaltest titer or persistent or recurrentsigns or symptoms probably indicatestreatment failure or reinfection. Treatsuch patients again for syphilis afterreevaluation for HIV infection.If nontreponemal test titers donot decline 4-fold within 6 monthsafter therapy, treatment failure is likely.Such patients should be evaluatedagain for HIV infection.

GONOCOCCALINFECTIONDiagnosis. About 600,000 newNeisseria gonorrhoeae infections occureach year in the United States. Mostinfections among men, such as urethritis,are symptomatic, and patientsseek treatment early enough to preventserious sequelae. Amongwomen, however, gonococcal infectionsare usually asymptomatic untilcomplications, such as pelvic inflammatorydisease (PID), have occurred.

In men with urethritis, Gramstaining of urethral secretions can establishthe diagnosis of gonococcal infectionby documenting the presenceof white blood cells with intracellulargram-negative diplococci. Nucleicacid amplification tests allow detectionof N gonorrhoeae in first-voidurine; in some settings, these testsmay be more sensitive than traditionalculture techniques.

Treatment. Because patientswho have gonococcal infections frequentlyhave coexisting Chlamydiatrachomatis infection, dual therapy isrecommended. In areas where coinfectionrates are low, physiciansmay prefer to test for Chlamydia beforetreatment. Patients who are unlikelyto return for follow-up shouldreceive dual therapy.

 Table 1 - Recommended regimens for uncomplicated gonococcal infections
Site of infection Drug Dosage

Cervix, urethra, or rectum* Cefixime† 400 mg PO (single dose)
  or  
  Ceftriaxone† 125 mg IM (single dose)
  or  
  Ciprofloxacin‡§ 500 mg PO (single dose)
  or  
  Ofloxacin‡§ 400 mg PO (single dose)
  or  
  Levofloxacin‡§ 250 mg PO (single dose)

  plus¶  
  Azithromycin 1 g PO (single dose)
  or  
  Doxycycline 100 mg PO bid for 7 d

Pharynx Ceftriaxone 125 mg IM (single dose)
  or  
  Ciprofloxacin§ 500 mg PO (single dose)

  plus¶  
  Azithromycin 1 g PO (single dose)
  or  
  Doxycycline 100 mg PO bid for 7 d

*Spectinomycin (2 g IM in a single dose) is useful for patients who cannot tolerate cephalosporins and quinolones. †Alternative single-dose cephalosporin regimens include ceftizoxime (500 mg IM), cefotaxime (500 mg IM), and cefoxitin (2 g IM) with probenecid (1 g PO). ‡Alternative single-dose quinolone regimens include gatifloxacin (400 mg PO), norfloxacin (800 mg PO), and lomefloxacin 400 mg PO). §Quinolones should not be used for infections acquired in Asia or the Pacific region, including Hawaii. Also, quinolones are not recommended for patients with infections acquired in California and other areas with an increased prevalence of quinolone resistance. ¶If chlamydial infection is not ruled out. Data from Centers for Disease Control and Prevention. MMWR. 2002.

Because many antimicrobialsare active against N gonorrhoeae, theguidelines are not intended to be acomprehensive list of all effectiveagents. Table 1 provides recommendedregimens for uncomplicatedgonococcal infections. Pharyngeal infectionsare more difficult to eradicatethan urogenital and anorectalinfections.

Follow-up. Patients who aretreated for uncomplicated gonorrheado not need to return for follow-up. Ifsymtoms persist after treatment, culturefor N gonorrhoeae is recommended.Test any gonococci isolated forantimicrobial susceptibility.

CHLAMYDIALINFECTIONDiagnosis. Chlamydial infectionis frequently asymptomatic. Inthe United States, the infection occursmost often among adolescentsand young adults. Screen sexuallyactive adolescent and young adultwomen for chlamydial infection during annual examinations, even ifsymptoms are not present. Also considerscreening older women withrisk factors, such as new or multiplesex partners.

Treatment. The recommendedregimens for chlamydial infection areazithromycin, 1 g PO in a single dose,or doxycycline, 100 mg PO bid for 7days. Alternative regimens are:

  • Erythromycin base, 500 mg PO qidfor 7 days.
  • Erythromycin ethylsuccinate,800 mg PO qid for 7 days.
  • Ofloxacin, 300 mg PO bid for 7 days.
  • Levofloxacin, 500 mg PO for 7 days.

Doxycycline costs less thanazithromycin; however, if you suspectthe patient may not comply with theregimen, azithromycin may be a betterchoice because it affords singledose,directly observed therapy. Advisepatients to abstain from sexual intercoursefor 7 days after single-dosetherapy or until completion of a 7-dayregimen. To reduce the risk of reinfection,also tell them to abstain untilall their sex partners are treated.

Follow-up. Unless symptomspersist or reinfection is suspected,retesting for Chlamydia is not necessaryafter treatment with doxycyclineor azithromycin. Consider retesting3 weeks after erythromycin therapyis completed.

PELVIC INFLAMMATORYDISEASEDiagnosis. Acute PID is difficultto diagnose because the signs andsymptoms vary widely. Many womenhave only subtle or mild symptoms. Because even mild PID can cause severesequelae, such as infertility andectopic pregnancy, maintain a lowthreshold of suspicion for the diagnosis.In sexually active young womenand other women at risk for STDs,empiric treatment is warranted if thefollowing criteria are present and noother cause of illness can be identified:

  • Uterine/adnexal tenderness.
  • Cervical motion tenderness.

Additional criteria that supportthe diagnosis of PID are an oral temperaturegreater than 38.3oC(101oF), abnormal cervical or vaginalmucopurulent discharge, thepresence of white blood cells onsaline microscopy of vaginal secretions,an elevated erythrocyte sedimentationrate, an elevated C-reactiveprotein level, and laboratorydocumentation of N gonorrhoeae orC trachomatis. Definitive criteriainclude:

  • Histopathologic evidence of endometritison endometrial biopsy.
  • Transvaginal sonography or otherimaging technique showing thickened,fluid-filled tubes with or withoutfree pelvic fluid or tubo-ovariancomplex.
  • Laparoscopic abnormalities consistentwith PID.
 Table 2 - Recommended regimens for pelvic inflammatory disease
Parenteral Oral 

Regimen A Regimen A 
Cefotetan, 2 g IV q12h Ofloxacin, 400 mg PO bid for 14 d 
or or 
Cefoxitin, 2 g IV q6h Levofloxacin, 500 mg PO once daily for 14 d 
plus  with or without 
Doxycycline, 100 mg PO or IV q12h*  Metronidazole, 500 mg PO bid for 14 d 

Regimen B  Regimen B 
Clindamycin, 900 mg IV q8h  Ceftriaxone, 250 mg IM (single dose) 
plus  or 
Gentamicin, IV or IM loading dose (2 mg/kg), followed by a maintenance dose (1.5 mg/kg) q8h. Single daily dosing may be substituted  Cefoxitin, 2 g IM (single dose), and probenecid, 1 g PO (single dose), administered concurrently 
Alternative regimens  or 
Ofloxacin, 400 mg IV q12h  Other parenteral third-generation cephalosporin eg, ceftizoxime or cefotaxime) 
or  plus 
Levofloxacin, 500 mg IV once daily  Doxycycline, 100 mg PO bid for 14 d 
with or without  with or without 
Metronidazole, 500 mg IV q8h  Metronidazole, 500 mg PO bid for 14 d 
Ampicillin/sulbactam, 3 g IV q6h    
plus    
Doxycycline, 100 mg PO or IV q12h*    
     

*Because pain is associated with infusion, administer doxycycline orally when possible, even if the patient is hospitalized. Data from Centers for Disease Control and Prevention. MMWR. 2002.

Treatment. Because PID is apolymicrobial infection-involving notonly N gonorrhoeae and C trachomatisbut also a host of mixed anaerobic andaerobic bacteria-broad-spectrumantibiotic coverage is required. Initiatetreatment as soon as you make thepresumptive diagnosis, because immediateantibiotic administration hasbeen shown to prevent long-term sequelae.Table 2 lists the recommendedparenteral and oral regimens.

Parenteral therapy may be discontinued24 hours after the patientimproves clinically. Continue oraltherapy (doxycycline, 100 mg bid) tocomplete a total of 14 days of therapy.In patients with tubo-ovarian abscess,many physicians use clindamycin ormetronidazole with doxycycline forcontinued therapy, rather than doxycyclinealone, to provide better anaerobiccoverage.

Routine hospitalization of adolescentswith PID is no longer recommended.Although the decision tohospitalize a patient remains an individual one, the latest CDC criteriaare:

  • Potential for surgical emergency,such as appendicitis.
  • Pregnancy.
  • Failure to respond to oral antimicrobialtherapy.
  • Inability to receive oral medications.
  • Severe illness, nausea and vomiting,or high fever.
  • Tubo-ovarian abscess.

Follow-up. If the patient doesnot show substantial clinical improvement(eg, defervescence; reduced director rebound abdominal tenderness;and reduced uterine, adnexal,and cervical motion tenderness) within3 days after therapy is started, additionaldiagnostic tests and/orsurgery are usually required. Someexperts recommend screening for Ngonorrhoeae and C trachomatis 4 to 6weeks after therapy is completed.

CHANCROIDDiagnosis. Painful genital ulcersand suppurative inguinal adenopathyare nearly pathognomonic for chancroid(Figure 3). Other diagnosticcriteria include negative results ofdarkfield examination of ulcer exudatefor T pallidum, serologic testingfor syphilis, and testing for herpessimplex virus. A definitive diagnosisrequires identification of Haemophilusducreyi on special culture media thatare not widely available.

Treatment. Effective treatmentof chancroid cures the infection, resolvessymptoms, and prevents transmission.The recommended regimensare:

  • Azithromycin, 1 g PO in a singledose.
  • Ceftriaxone, 250 mg IM in a singledose.
  • Ciprofloxacin, 500 mg PO bid for3 days.
  • Erythromycin base, 500 mg PO tidfor 7 days.

Follow-up. Reexamine patients3 to 7 days after therapy is initiated.With successful treatment, ulcers improvesymptomatically within 3 daysand objectively within 7 days aftertherapy. Large ulcers may requiremore than 2 weeks to heal. Reasonsfor treatment failure include concurrentinfection with another STD, noncompliancewith the therapeutic regimen,and infection with an antimicrobial-resistant strain of H ducreyi.

References:

REFERENCE:1. Centers for Disease Control and Prevention. Sexuallytransmitted diseases treatment guidelines2002. MMWR. 2002;51(RR-6):1-80.