Warning:

This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:

• STD Treatment Guidelines   at http://www.cdc.gov/STD/treatment

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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

PELVIC INFLAMMATORY DISEASE
     
     PID comprises a spectrum of inflammatory disorders of the
upper genital tract among women and may include any combination of
endometritis, salpingitis, tubo-ovarian abscess, and pelvic
peritonitis. Sexually transmitted organisms, especially N.
gonorrhoeae and C. trachomatis, are implicated in the majority of
cases; however, microorganisms that can be part of the vaginal
flora, such as anaerobes, G. vaginalis, H. influenzae, enteric
Gram-negative rods, and Streptococcus agalactiae also can cause
PID. Some experts also believe that M. hominis and U. urealyticum
are etiologic agents of PID.

Diagnostic Considerations
     
     Because of the wide variation in many symptoms and signs among
women with this condition, a clinical diagnosis of acute PID is
difficult. Many women with PID exhibit subtle or mild symptoms that
are not readily recognized as PID. Consequently, delay in diagnosis
and effective treatment probably contributes to inflammatory
sequelae in the upper reproductive tract. Laparoscopy can be used
to obtain a more accurate diagnosis of salpingitis and a more
complete bacteriologic diagnosis. However, this diagnostic tool is
often neither readily available for acute cases nor easily
justifiable when symptoms are mild or vague. Moreover, laparoscopy
will not detect endometritis and may not detect subtle inflammation
of the fallopian tubes. Consequently, the diagnosis of PID is
usually made on the basis of clinical findings.

     The clinical diagnosis of acute PID is also imprecise. Data
indicate that a clinical diagnosis of symptomatic PID has a
positive predictive value (PPV) for salpingitis of 65%-90% when
compared with laparoscopy as the standard. The PPV of a clinical
diagnosis of acute PID varies depending on epidemiologic
characteristics and the clinical setting, with higher PPV among
sexually active young (especially teenage) women and among patients
attending STD clinics or from settings with high rates of gonorrhea
or chlamydia. In all settings, however, no single historical,
physical, or laboratory finding is both sensitive and specific for
the diagnosis of acute PID (i.e., can be used both to detect all
cases of PID and to exclude all women without PID). Combinations of
diagnostic findings that improve either sensitivity (detect more
women who have PID) or specificity (exclude more women who do not
have PID) do so only at the expense of the other. For example,
requiring two or more findings excludes more women without PID but
also reduces the number of women with PID who are detected.

     Many episodes of PID go unrecognized. Although some women may
have asymptomatic PID, others are undiagnosed because the patient
or the health-care provider fails to recognize the implications of
mild or nonspecific symptoms or signs, such as abnormal bleeding,
dyspareunia, or vaginal discharge ("atypical PID"). Because of the
difficulty of diagnosis and the potential for damage to the
reproductive health of women even by apparently mild or atypical
PID, experts recommend that providers maintain a low threshold of
diagnosis for PID. Even so, the long-term outcome of early
treatment of women with asymptomatic or atypical PID on important
clinical outcomes is unknown. The following recommendations for
diagnosing PID are intended to help health-care providers recognize
when PID should be suspected and when they need to obtain
additional information to increase diagnostic certainty. These
recommendations are based in part on the fact that diagnosis and
management of other common causes of lower abdominal pain (e.g.,
ectopic pregnancy, acute appendicitis, and functional pain) are
unlikely to be impaired by initiating empiric antimicrobial therapy
for PID.


Minimum Criteria
     Empiric treatment of PID should be instituted on the basis of
the presence of all of the following three minimum clinical
criteria for pelvic inflammation and in the absence of an
established cause other than PID:

--   Lower abdominal tenderness,

--   Adnexal tenderness, and

--   Cervical motion tenderness.

Additional Criteria
     For women with severe clinical signs, more elaborate
diagnostic evaluation is warranted because incorrect diagnosis and
management may cause unnecessary morbidity. These additional
criteria may be used to increase the specificity of the diagnosis.

     Listed below are the routine criteria for diagnosing PID:

--   Oral temperature greater than 38.3 C,

--   Abnormal cervical or vaginal discharge,

--   Elevated erythrocyte sedimentation rate,

--   Elevated C-reactive protein,

--   Laboratory documentation of cervical infection with N.
     gonorrhoeae or C. trachomatis.

     Listed below are the elaborate criteria for diagnosing PID:

--   Histopathologic evidence of endometritis on endometrial
     biopsy,

--   Tubo-ovarian abscess on sonography or other radiologic tests,

--   Laparoscopic abnormalities consistent with PID.

     Although initial treatment decisions can be made before
bacteriologic diagnosis of C. trachomatis or N. gonorrhoeae
infection, such a diagnosis emphasizes the need to treat sex
partners.


Treatment

     PID therapy regimens must provide empiric, broad-spectrum
coverage of likely pathogens. Antimicrobial coverage should include
N. gonorrhoeae, C. trachomatis, Gram-negative facultative bacteria,
anaerobes, and streptococci. Although several antimicrobial
regimens have proven effective in achieving clinical and
microbiologic cure in randomized clinical trials with short-term
follow-up, few studies have been done to assess and compare
elimination of infection of the endometrium and fallopian tubes, or
the incidence of long-term complications such as tubal infertility
and ectopic pregnancy.

     No single therapeutic regimen has been established for persons
with PID. When selecting a treatment regimen, health-care providers
should consider availability, cost, patient acceptance, and
regional differences in antimicrobial susceptibility of the likely
pathogens.

     Many experts recommend that all patients with PID be
hospitalized so that supervised treatment with parenteral
antibiotics can be initiated. Hospitalization is especially
recommended when the following criteria are met:

--   The diagnosis is uncertain, and surgical emergencies such as
     appendicitis and ectopic pregnancy cannot be excluded,

--   Pelvic abscess is suspected,

--   The patient is pregnant,

--   The patient is an adolescent (among adolescents, compliance
     with therapy is unpredictable),

--   The patient has HIV infection,

--   Severe illness or nausea and vomiting preclude outpatient
     management,

--   The patient is unable to follow or tolerate an outpatient
     regimen,

--   The patient has failed to respond clinically to outpatient
     therapy,

--   Clinical follow-up within 72 hours of starting antibiotic
     treatment cannot be arranged.

Inpatient Treatment
     Experts have experience with both of the following regimens.
Also, there are multiple randomized trials demonstrating the
efficacy of each regimen.

Regimen A -
     Cefoxitin 2 g IV every 6 hours or cefotetan 2 g IV every 12
     hours,
                         PLUS
     Doxycycline 100 mg IV or orally every 12 hours.

NOTE: This regimen should be continued for at least 48 hours
after the patient demonstrates substantial clinical improvement,
after which doxycycline 100 mg orally 2 times a day should be
continued for a total of 14 days. Doxycycline administered orally
has bioavailability similar to that of the IV formulation and may
be administered if normal gastrointestinal function is present.

     Clinical data are limited for other second- or
third-generation cephalosporins (e.g., ceftizoxime, cefotaxime, and
ceftriaxone), which might replace cefoxitin or cefotetan, although
many authorities believe they also are effective therapy for PID.
However, they are less active than cefoxitin or cefotetan against
anaerobic bacteria.

Regimen B -
     Clindamycin 900 mg IV every 8 hours,
                     PLUS
     Gentamicin loading dose IV or IM (2 mg/kg of body weight)
     followed by a maintenance dose (1.5 mg/kg) every 8 hours.

NOTE:This regimen should be continued for at least 48 hours
after the patient demonstrates substantial clinical improvement,
then followed with doxycycline 100 mg orally 2 times a day or
clindamycin 450 mg orally 4 times a day to complete a total of 14
days of therapy. When tubo-ovarian abscess is present, many
health-care providers use clindamycin for continued therapy rather
than doxycycline, because it provides more effective anaerobic
coverage. Clindamycin administered intravenously appears to be
effective against C. trachomatis infection; however, the
effectiveness of oral clindamycin against C. trachomatis has not
been determined.

     Alternative Inpatient Regimens. Limited data support the use
of other inpatient regimens, but two regimens have undergone at
least one clinical trial and have broad-spectrum coverage.
Ampicillin/sulbactam plus doxycycline has good anaerobic coverage
and appears to be effective for patients with a tubo-ovarian
abscess. Intravenous ofloxacin has been studied as a single agent.
A regimen of ofloxacin plus either clindamycin or metronidazole
provides broad-spectrum coverage. Evidence is insufficient to
support the use of any single agent regimen for inpatient treatment
of PID.

Outpatient Treatment
     Clinical trials of outpatient regimens have provided little
information regarding intermediate and long-term outcomes. The
following regimens provide coverage against the common etiologic
agents of PID, but evidence from clinical trials supporting their
use is limited. The second regimen provides broader coverage
against anaerobic organisms but costs substantially more than the
other regimen. Patients who do not respond to outpatient therapy
within 72 hours should be hospitalized to confirm the diagnosis and
to receive parenteral therapy.

Regimen A -
     Cefoxitin 2 g IM plus probenecid, 1 g orally in a single dose
     concurrently, or ceftriaxone 250 mg IM or other parenteral
     third-generation cephalosporin (e.g., ceftizoxime or cefotaxime),
                               PLUS
     Doxycycline 100 mg orally 2 times a day for 14 days.

Regimen B -
     Ofloxacin 400 mg orally 2 times a day for 14 days,
                               PLUS
     Either clindamycin 450 mg orally 4 times a day, or
     metronidazole 500 mg orally 2 times a day for 14 days.

     Clinical trials have demonstrated that the cefoxitin regimen
is effective in obtaining short-term clinical response. Fewer data
support the use of ceftriaxone or other third-generation
cephalosporins, but, based on their similarities to cefoxitin, they
also are considered effective. No data exist regarding the use of
oral cephalosporins for the treatment of PID.

     Ofloxacin is effective against both N. gonorrhoeae and C.
trachomatis. One clinical trial demonstrated the effectiveness of
oral ofloxacin in obtaining short-term clinical response with PID.
Despite results of this trial, there is concern related to
ofloxacin's lack of anaerobic coverage; the addition of clindamycin
or metronidazole provides this coverage. Clindamycin, but not
metronidazole, further enhances the Gram-positive coverage of the
regimen.

     Alternative Outpatient Regimens. Information regarding other
outpatient regimens is limited. The combination of
amoxicillin/clavulanic acid plus doxycycline was effective in
obtaining short-term clinical response in one clinical trial, but
many of the patients had to discontinue the regimen because of
gastrointestinal symptoms.

Follow-Up
     
     Hospitalized patients receiving IV therapy should show
substantial clinical improvement (e.g., defervescence, reduction in
direct or rebound abdominal tenderness, and reduction in uterine,
adnexal, and cervical motion tenderness) within 3-5 days of
initiation of therapy. Patients who do not demonstrate improvement
within this time period usually require further diagnostic workup
or surgical intervention, or both.

     If the provider elects to prescribe outpatient therapy,
follow-up examination should be performed within 72 hours, using
the criteria for clinical improvement previously described.

     Because of the risk for persistent infection, particularly
with C. trachomatis, patients should have a microbiologic
re-examination 7-10 days after completing therapy. Some experts
also recommend rescreening for C. trachomatis and N. gonorrhoeae 4-
6 weeks after completing therapy.

Management of Sex Partners

     Evaluation and treatment of sex partners of women who have PID
is imperative because of the risk for re-infection and the high
likelihood of urethral gonococcal or chlamydial infection of the
partner.

     Since nonculture, and perhaps culture, tests for C.
trachomatis and N. gonorrhoeae are thought to be insensitive among
asymptomatic men, sex partners should be treated empirically with
regimens effective against both of these infections -- regardless
of the apparent etiology of PID or pathogens isolated from the
infected woman.

     Even in clinical settings in which only women are seen,
special arrangements should be made to provide care for male sex
partners of women with PID. When this is not feasible, health-care
providers should ensure that sex partners are appropriately
referred for treatment.

Special Considerations

Pregnancy -
     Pregnant women with suspected PID should be hospitalized and
treated with parenteral antibiotics.

HIV Infection -
     Differences in the clinical manifestations of PID between
HIV-infected women and noninfected women have not been described
clearly. However, in one study, HIV-infected women with PID tended
to have a leukopenia or a lesser leukocytosis than women who were
not HIV-infected, and they were more likely to require surgical
intervention. HIV-infected women who develop PID should be managed
aggressively. Hospitalization and inpatient therapy with one of the
IV antimicrobial regimens described in this report is recommended.

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