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1993 Sexually Transmitted Diseases Treatment Guidelines


09/24/1993

SUGGESTED CITATION
Centers for Disease Control and Prevention. 1993 Sexually
transmitted diseases treatment guidelines. MMWR 1993;42(No. RR-14):
{inclusive page numbers}.

CIO Responsible for this publication:
National Center for Prevention Services,
Division of Sexually Transmitted Diseases and HIV Prevention

Gonococcal Infections Among Adolescents and Adults
     
     An estimated 1 million new infections with N. gonorrhoeae
occur in the United States each year. Most infections among men
produce symptoms that cause the person to seek curative treatment
soon enough to prevent serious sequelae -- but not soon enough to
prevent transmission to others. Many infections among women do not
produce recognizable symptoms until complications such as PID have
occurred. PID, whether symptomatic or asymptomatic, can cause tubal
scarring leading to infertility or ectopic pregnancy. Because
gonococcal infections among women are often asymptomatic, a primary
measure for controlling gonorrhea in the United States has been the
screening of high-risk women.

Uncomplicated Gonococcal Infections

Recommended Regimens -
     Ceftriaxone 125 mg IM in a single dose
                       or
     Cefixime 400 mg orally in a single dose
                       or
     Ciprofloxacin 500 mg orally in a single dose
                       or
     Ofloxacin 400 mg orally in a single dose
                       PLUS
     A regimen effective against possible coinfection with C.
     trachomatis, such as doxycycline 100 mg orally 2 times a day for 7
     days.

     Many antibiotics are safe and effective for treating
gonorrhea, eradicating N. gonorrhoeae, ending the possibility of
further transmission, relieving symptoms, and reducing the chances
of sequelae.

     Selection of a treatment regimen for N. gonorrhoeae infection
requires consideration of the anatomic site of infection,
resistance of N. gonorrhoeae strains to antimicrobials, the
possibility of concurrent infection with C. trachomatis, and the
side effects and costs of the various treatment regimens.

     Because coinfection with C. trachomatis is common, persons
treated for gonorrhea should be treated presumptively with a
regimen that is effective against C. trachomatis (see Chlamydial
Infections).

     Most experts agree that other regimens recommended for the
treatment of C. trachomatis infection are also likely to be
satisfactory for the treatment of co- infection (see Chlamydial
Infections). However, studies have not been conducted to
investigate possible interactions between other treatments for N.
gonorrhoeae and C. trachomatis, including interactions influencing
the effectiveness and side effects of cotreatment.

     In clinical trials, these recommended regimens cured greater
than 95% of anal and genital infections; any of the regimens may be
used for uncomplicated anal or genital infection. Published studies
indicate that ceftriaxone 125 mg and ciprofloxacin 500 mg can cure
greater than or equal to 90% of pharyngeal infections. If
pharyngeal infection is a concern, one of these two regimens should
be used.

     Ceftriaxone in a single dose of either 125 mg or 250 mg
provides sustained, high bactericidal levels in the blood.
Extensive clinical experience indicates that both doses are safe
and effective for the treatment of uncomplicated gonorrhea at all
sites. In the past, the 250 mg dose has been recommended on the
supposition that the routine use of a higher dose may forestall the
development of resistance. However, on the basis of ceftriaxone's
activity against N. gonorrhoeae, its pharmacokinetics, and the
results in clinical trials of doses as low as 62.5 mg, the 125 mg
dose appears to have a therapeutic reserve at least as large as
that of other accepted treatment regimens. No ceftriaxone-resistant
strains of N. gonorrhoeae have been reported. The drawbacks of
ceftriaxone are that it is expensive, currently unavailable in
vials of less than 250 mg, and must be administered by injection.
Some health-care providers believe that the discomfort of the
injection may be reduced by using 1% lidocaine solution as a
diluent. Ceftriaxone also may abort incubating syphilis, a concern
when gonorrhea treatment is not accompanied by a 7-day course of
doxycycline or erythromycin for the presumptive treatment of
chlamydia.

     Cefixime has an antimicrobial spectrum similar to that of
ceftriaxone, but the 400 mg oral dose does not provide as high nor
as sustained a bactericidal level as does 125 mg of ceftriaxone.
Cefixime appears to be effective against pharyngeal gonococcal
infection, but few patients with pharyngeal infection have been
included in studies. No gonococcal strains resistant to cefixime
have been reported. The advantage of cefixime is that it can be
administered orally. It is not known if the 400 mg dose can cure
incubating syphilis.

     Ciprofloxacin at a dose of 500 mg provides sustained
bactericidal levels in the blood. Clinical trials have demonstrated
that both 250 mg and 500 mg doses are safe and effective for the
treatment of uncomplicated gonorrhea at all sites. Most clinical
experience in the United States has been with the 500 mg dose.
Ciprofloxacin can be administered orally and is less expensive than
ceftriaxone. No resistance has been reported in the United States,
but strains with decreased susceptibility to some quinolones are
becoming common in Asia and have been reported in North America.
The 500 mg dose is recommended, rather than the 250 mg dose,
because of the trend toward decreasing susceptibility to quinolones
and because of rare reports of treatment failure. Quinolones are
contraindicated for pregnant or nursing women and for persons less
than or equal to 17 years of age on the basis of information from
animal studies. Quinolones are not active against T. pallidum.

     Ofloxacin is active against N. gonorrhoeae, has favorable
pharmacokinetics, and the 400 mg dose has been effective for the
treatment of uncomplicated anal and genital gonorrhea. In published
studies a 400 mg dose cured 22 (88%) of 25 pharyngeal infections.

Alternative Regimens -

--   Spectinomycin 2 g IM in a single dose. Spectinomycin has the
     disadvantages of being injectable, expensive, inactive against T.
     pallidum, and relatively ineffective against pharyngeal gonorrhea.
     In addition, resistant strains have been reported in the United
     States. However, spectinomycin remains useful for the treatment of
     patients who can tolerate neither cephalosporins nor quinolones.

--   Injectable cephalosporin regimens other than ceftriaxone 125
     mg that have demonstrated efficacy against uncomplicated anal or
     genital gonococcal infections include these injectable
     cephalosporins: ceftizoxime 500 mg IM in a single dose; cefotaxime
     500 mg IM in a single dose; cefotetan 1 g IM in a single dose; and
     cefoxitin 2 g IM in a single dose.

     None of these injectable cephalosporins offers any advantage
     compared with ceftriaxone, and there is less clinical experience
     with them for the treatment of uncomplicated gonorrhea. Of these
     four regimens, ceftizoxime 500 mg appears to be the most effective
     according to cumulative experience in published clinical trials.

--   Oral cephalosporin regimens other than cefixime 400 mg include
     cefuroxime axetil 1 g orally in a single dose and cefpodoxime
     proxetil 200 mg orally in a single dose. These two regimens have
     anti-gonococcal activity and pharmacokinetics less favorable than
     the 400 mg cefixime regimen, and there is less clinical experience
     with them in the treatment of gonorrhea. They have not been very
     effective against pharyngeal infections among the few patients
     studied.

--   Quinolone regimens other than ciprofloxacin 500 mg and
     ofloxacin 400 mg include enoxacin 400 mg orally in a single dose;
     lomefloxacin 400 mg orally in a single dose; and norfloxacin 800 mg
     orally in a single dose. They appear to be safe and effective for
     the treatment of uncomplicated gonorrhea, but none appears to offer
     any advantage over ciprofloxacin at a dose of 500 mg or ofloxacin
     at 400 mg.

     Enoxacin and norfloxacin are active against N. gonorrhoeae,
     have favorable pharmacokinetics, and have been effective in
     clinical trials, but there is minimal experience with their use in
     the United States. Lomefloxacin is effective against N. gonorrhoeae
     and has very favorable pharmacokinetics, but there are few
     published clinical studies to support its use for the treatment of
     gonorrhea, and there is little experience with its use in the
     United States.

     Many other antimicrobials are active against N. gonorrhoeae.
These guidelines are not intended to be a comprehensive list of all
effective treatment regimens.

Other Management Considerations -
     Persons treated for gonorrhea should be screened for syphilis
by serology when gonorrhea is first detected. Gonorrhea treatment
regimens that include ceftriaxone or a 7-day course of either
doxycycline or erythromycin may cure incubating syphilis, but few
data relevant to this topic are available.

Follow-Up -
     Persons who have uncomplicated gonorrhea and who are treated
with any of the regimens in these guidelines need not return for a
test-of-cure. Those persons with symptoms persisting after
treatment should be evaluated by culture for N. gonorrhoeae, and
any gonococci isolated should be tested for antimicrobial
susceptibility. Infections detected after treatment with one of the
recommended regimens more commonly occur because of reinfection
rather than treatment failure, indicating a need for improved sex
partner referral and patient education. Persistent urethritis,
cervicitis, or proctitis also may be caused by C. trachomatis and
other organisms.

Management of Sex Partners -
     Patients should be instructed to refer sex partners for
evaluation and treatment. Sex partners of symptomatic patients who
have N. gonorrhoeae infection should be evaluated and treated for
N. gonorrhoeae and C. trachomatis infections, if their last sexual
contact with the patient was within 30 days of onset of the
patient's symptoms. If the index patient is asymptomatic, sex
partners whose last sexual contact with the patient was within 60
days of diagnosis should be evaluated and treated. Health-care
providers should treat the most recent sex partner, if last sexual
intercourse took place before those time periods.

     Patients should be instructed to avoid sexual intercourse
until patient and partner(s) are cured. In the absence of
microbiologic test-of-cure, this means until therapy is completed
and patient and partner(s) are without symptoms.

Special Considerations -

Allergy, Intolerance, or Adverse Reactions
     Persons who cannot tolerate cephalosporins should, in general,
be treated with quinolones. Those who can take neither
cephalosporins nor quinolones should be treated with spectinomycin,
except for those patients who are suspected or known to have
pharyngeal infection. For pharyngeal infections among persons who
can tolerate neither a cephalosporin nor quinolones, some studies
suggest that trimethoprim/ sulfamethoxazole may be effective at a
dose of 720 mg trimethoprim/3,600 mg sulfamethoxazole orally once
a day for 5 days.

Pregnancy -
     Pregnant women should not be treated with quinolones or
tetracyclines. Those infected with N. gonorrhoeae should be treated
with a recommended or alternate cephalosporin. Women who cannot
tolerate a cephalosporin should be administered a single dose of 2
g of spectinomycin IM. Erythromycin is the recommended treatment
for presumptive or diagnosed C. trachomatis infection during
pregnancy (see Chlamydial Infections).

HIV Infection -
     Persons with HIV infection and gonococcal infection should
receive the same treatment as persons not infected with HIV.

Gonococcal Conjunctivitis
     Only one North American study of the treatment of gonococcal
conjunctivitis among adults has been published in recent years. In
that study, 12 of 12 patients responded favorably to a single 1 g
IM injection of ceftriaxone. The recommendations that follow
reflect the opinions of expert consultants.

Treatment -

Recommended Regimen -
     A single, 1 g dose of ceftriaxone should be administered IM,
     and the infected eye should be lavaged with saline solution once.

Management of Sex Partners -
     As for uncomplicated infections, patients should be instructed
to refer sex partner(s) for evaluation and treatment (see
Uncomplicated Gonococcal Infections, Management of Sex Partners).

Disseminated Gonococcal Infection
     Disseminated gonococcal infection (DGI) results from
gonococcal bacteremia, often resulting in petechial or pustular
acral skin lesions, asymmetrical arthalgias, tenosynovitis or
septic arthritis -- and is occasionally complicated by hepatitis
and, rarely, by endocarditis or meningitis. Strains of N.
gonorrhoeae that cause DGI tend to cause little genital
inflammation. These strains have become uncommon in the United
States during the past decade.

     No North American studies of the treatment of DGI have been
published recently. The recommendations that follow reflect the
opinions of expert consultants.

Treatment -
     Hospitalization is recommended for initial therapy, especially
for patients who cannot be relied on to comply with treatment, for
those for whom the diagnosis is uncertain, and for those who have
purulent synovial effusions or other complications. Patients should
be examined for clinical evidence of endocarditis and meningitis.
Patients treated for DGI should be treated presumptively for
concurrent C. trachomatis infection.

Recommended Initial Regimen -
     Ceftriaxone 1 g IM or IV every 24 hours.
     
Alternative Initial Regimens
     Cefotaxime 1 g IV every 8 hours
                  or
     Ceftizoxime 1 g IV every 8 hours
                  or
     For persons allergic to B-lactam drugs:
     Spectinomycin 2 g IM every 12 hours.

     All regimens should be continued for 24-48 hours after
improvement begins; then therapy may be switched to one of the
following regimens to complete a full week of antimicrobial
therapy:
     Cefixime 400 mg orally 2 times a day
                   or
     Ciprofloxacin 500 mg orally 2 times a day.

NOTE: Ciprofloxacin is contraindicated for children,
adolescents less than or equal to 17 years of age, and pregnant and
lactating women.

Management of Sex Partners
     Gonococcal infection is often asymptomatic in sex partners of
patients with DGI. As for uncomplicated infections, patients should
be instructed to refer sex partner(s) for evaluation and treatment
(see Uncomplicated Gonococcal Infections, Management of Sex
Partners).

Gonococcal Meningitis and Endocarditis

Recommended Initial Regimen -
     1-2 g of ceftriaxone IV every 12 hours.

     Therapy for meningitis should be continued for 10-14 days and
for endocarditis for at least 4 weeks. Treatment of complicated DGI
should be undertaken in consultation with an expert.

Management of Sex Partners -
     As for uncomplicated infections, patients should be instructed
to refer sex partners for evaluation and treatment (see
Uncomplicated Gonococcal Infections, Management of Sex Partners).



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