An abscess may form in the pelvic or abdominal cavity and in one or both fallopian
tubes. Chronic abdominal pain develops in 18% of women with PID and may be the
result of pelvic adhesions surrounding the tubes and ovaries. After a single episode
of PID, tubal occlusion and fibrosis secondary to fallopian tube inflammation
(salpingitis) result in 12% infertility, 25% infertility after two episodes, and 50%
infertility after three or more episodes.
42 Other sequelae include ectopic pregnancy
(9%) and chronic pelvic pain (18%).
48 The risk of ectopic pregnancy is increased
approximately eightfold after one or more episodes of PID.
The peripheral WBC count was mildly elevated (11,000/μL) with 70% polymorphonuclear leukocytes. Does
H.C. have PID? How should she be treated?
Antimicrobial Regimens Recommended by the CDC for Treatment of Acute
Treatment Setting, Drugs, Schedule Advantage Disadvantage
Inpatient (Parenteral) Therapy
Cefotetan 2 g IV every 12 hours OR
cefoxitin 2 g IV every 6 hours PLUS
Continue doxycycline (100 mg PO twice
daily) after discharge to complete 14 days
Clindamycin 900 mg IV every 8 hours
PLUS gentamicin loading dose IV or IM (2
mg/kg) followed by a maintenance dose of
Ampicillin/sulbactam 3 g IV every 6 hours
PLUS doxycycline 100 mg PO or IV every
Ceftriaxone 250 mg IM in a single dose
PLUS doxycycline 100 mg PO twice daily
metronidazole 500 mg PO twice daily for 14
days OR cefoxitin 2 g IM in a single dose
and probenecid, 1 g PO administered
concurrently in a single dose PLUS
doxycycline 100 mg PO twice daily for 14
days WITH or WITHOUT metronidazole
500 mg PO twice daily for 14 days OR
other parenteral third-generation
cephalosporins (e.g., ceftizoxime or
cefotaxime) PLUS doxycycline 100 mg PO
twice daily for 14 days WITH or
WITHOUT metronidazole 500 mg PO
bSingle daily dosing (3–5 mg/kg) may be substituted.
cConsider for mild-to-moderate acute PID.
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137.
Although fever and leukocytosis are often absent in mild or subacute PID, these
findings in a woman with uterine and adnexal tenderness with cervical exudate
increases the likelihood of acute PID. Recommended treatment regimens for PID are
listed in Table 72-2 and should be initiated immediately after diagnosis of PID to
prevent clinical sequelae; confirmation of the actual pathogen rarely takes place.
Patients such as H.C. with mild-to-moderate PID can be hospitalized and treated with
parenteral antibiotics; however, clinical efficacy and overall outcomes are equal
between parental and oral therapy, and H.C. could also be treated on an outpatient
basis. For inpatient treatment, the CDC recommends either intravenous (IV) cefotetan
2 g every 12 hours or IV cefoxitin 2 g every 6 hours for at least 24 hours beyond the
first signs of clinical improvement along with doxycycline 100 mg every 12 hours.
Once clinical improvement is noted, parenteral therapy may be discontinued and PO
doxycycline 100 mg every 12 hours can continue to complete 14 days of therapy. For
outpatient treatment, the CDC guidelines recommend either IM ceftriaxone 250 mg as
a single dose or IM cefoxitin 2 g as a single dose (with probenecid 1 g PO for one
dose) plus PO doxycycline 100 mg twice a day for 14 days with or without PO
metronidazole 500 mg twice daily for 14 days.
2 A tetracycline derivative or an
alternative agent that is active against C. trachomatis should be included in the
treatment of PID; however, monotherapy with a tetracycline is not recommended
because of the lack of activity against gram-negative aerobic and anaerobic
organisms and N. gonorrhoeae. The addition of metronidazole, which covers
anaerobic bacteria, should also be considered; anaerobes have been isolated from
the upper reproductive tract of women with PID and may cause tubal
49 Metronidazole is widely used by clinicians, because
BV is frequently associated with PID.
2 Fluoroquinolones, such as levofloxacin and
ofloxacin, are no longer recommended for the treatment of PID because of the
increase in prevalence of QRNG in the United States.
Both oral and IV doxycycline have similar bioavailability; therefore, doxycycline
should be given PO whenever possible.
2 Substantial clinical improvement is usually
seen within 3 days after initiation of therapy. Clindamycin plus gentamicin can be
used alternatively in penicillin-allergic and pregnant women.
sexually active, any sexual partners within the previous 60 days (or if >60 days, then
the most recent sexual partner) should be empirically treated because of the risk of
gonococcal or chlamydial urethritis as well as to reduce the risk of reinfection.
Disseminated Gonococcal Infection
isolated from the throat, cervix, blood, and synovial fluid. A chest radiograph, echocardiogram, and
S.P.’s signs, symptoms, and laboratory findings are consistent with gonococcal
bacteremia, which today occurs in less than 1% of women and men with gonorrhea.
The most common manifestation of gonococcemia is the gonococcal arthritis–
dermatitis syndrome or DGI exhibited by S.P. Symptoms include fever, occasional
chills, a mild tenosynovitis of the small joints, and skin lesions; the latter primarily
involving the distal extremities are petechial, papular, pustular, and hemorrhagic in
Diagnosis of DGI is made by NAAT or culture of specimen from routine sites of
gonococcal infections (e.g., urethra, cervix, pharynx, and rectum), as well as culture
from disseminated sites of infection (e.g., synovial fluid, blood, skin, and CNS).
However, blood cultures are positive in only 33% of DGI cases, even when culture
samples are obtained early in the course of the infection.
from blood cultures may be attributable to the low inoculum or intermittent
CASE 72-4, QUESTION 2: How should S.P. be managed? How quickly willshe respond to therapy?
Patients like S.P. with gonococcal arthritis and bacteremia should be hospitalized
for treatment with ceftriaxone 1 g IV or IM daily until substantial clinical
improvement is sustained for 24 to 48 hours, at which time therapy may be switched
to an oral agent guided by antimicrobial susceptibility for a total treatment course of
Initiation of treatment should also include azithromycin
1 g PO in a single dose. Symptoms and signs of tenosynovitis should be improved
markedly within 48 hours. Septic gonococcal arthritis with purulent synovial fluid
may require repeated aspiration and resolves more slowly.
Treatment of Disseminated Gonococcal Infection
b—Ceftriaxone 1 g IV or IM every 24 hours
b—Cefotaxime 1 g IV q8h or ceftizoxime 1 g IV every 8 hours
Cefixime 400 mg PO twice daily
aParenteral treatment should be continued for 24 to 48 hours beyond clinical improvement.
bTreatment should include a single dose of Azithromycin 1 g PO.
cTreat for 7 days after switching from parenteral therapy.
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137.
CASE 72-4, QUESTION 3: How should gonococcal endocarditis and meningitis be treated?
Treatment of Gonococcal Endocarditis and Meningitis
Gonococcal endocarditis and meningitis, occurring in only 1% to 3% of DGIs,
require high-dose IV therapy, such as ceftriaxone (1–2 g IV every 12–24 hours), for
10 to 14 days in the case of meningitis and for at least 4 weeks in the case of
2 Like other gonococcal infections, a single dose of azithromycin 1 g PO
Neonatal Disseminated Gonococcal Infection: Treatment
CASE 72-4, QUESTION 4: How should neonatal DGI and meningitis be managed?
Neonatal DGI and meningitis can be treated with either ceftriaxone 25 to 50 mg/kg
(IV or IM) daily or cefotaxime 25 mg/kg (IV or IM) every 12 hours. Treatment is for
7 days for DGI; however, meningitis requires 10 to 14 days of treatment.
ceftriaxone is also effective in the treatment of neonatal DGI and meningitis,
cefotaxime is considered a safer choice in the neonatal population.
The rate of reported Chlamydia infections has climbed steadily each year since the
1980s, and it is the most commonly reported STD in the United States. During 1993
to 2012, the reported rate of chlamydial infections increased from 178 to 453.3 cases
4 This increase may be attributable to the increased
development and use of more sensitive screening tests, improved national reporting
efforts, or a true increase in the incidence of disease.
In 2013, the United States saw
the rate of chlamydial infections decrease for the first time to 446.6 cases per
4 Women are 3 times more likely than men to be infected with Chlamydia—
623.1 cases versus 262.6 cases per 100,000 individuals, respectively, in 2013.
to 2013, the infection rate among men increased 21% compared with 6.2% in
women. The highest rate of infection is in women 15 to 19 years (3,043.3 cases per
100,000 females) and in men 20 to 24 years (1,325.6 cases per 100,000 males).
left untreated, chlamydial infection in women can lead to serious sequelae, such as
PID, ectopic pregnancy, and infertility. Asymptomatic infection is also observed in
both men and women; however, routine screening is recommended for sexually
active women up to 25 years of age and older women with risk factors for infection
(e.g., multiple sexual partners or having a new sexual partner). Screening sexually
active men for C. trachomatis can be considered in settings or populations with a
high prevalence of the infection (e.g., MSM populations).
C. trachomatis, an intracellular obligate organism, can be diagnosed either by
culture, direct immunofluorescence assay (DFA), enzyme immunoassay (EIA), or
NAAT of endocervical or male urethral swabs.
12 However, C. trachomatis is a
difficult organism to demonstrate in clinical specimens because cell culture
techniques are not readily available to the practitioner. Because few practitioners
have access to facilities for isolation of C. trachomatis, most chlamydial infections
are diagnosed and treated based on clinical impression and laboratory techniques.
Nonculture diagnostic tests, such as NAATs, DFAs, and EIAs, are generally
sensitive methods for detecting C. trachomatis. Ligase chain reaction and PCR are
two NAATs with wide commercial availability, are relatively simple to use, can be
performed using urine or genital swab specimens, and are more sensitive than nonNAATs.
15 NAATs are approximately 20% to 35% more sensitive than EIAs and
DFAs and are the recommended test method for detection of C. trachomatis in men
and women with and without symptoms.
16 A test-of-cure is not necessary unless
patient compliance is questionable, symptoms persist, or reinfection is suspected.
Repeat testing with NAATs fewer than 3 weeks after initiation of treatment is not
recommended because false-negative results may occur as a result of undetectable C.
trachomatis organisms. Moreover, false positives may occur with repeat NAATs
with the continued excretion of dead organisms.
A variety of clinical syndromes are caused by C. trachomatis, including cervicitis,
urethritis, bartholinitis, endometritis, salpingitis, and perihepatitis in women, and
urethritis, epididymitis, prostatitis, proctitis, and Reiter syndrome in men.
spectrum of chlamydial infections closely resembles those caused by the gonococcus,
which is why many patients presenting with these syndromes are treated with drugs
effective against both organisms.
There is controversy in how C. trachomatis is cultured and what the in vitro results
mean clinically, especially in the 10% to 15% of cases that fail treatment.
thus uses cure rates instead of microbial susceptibilities to make treatment
recommendations. Only azithromycin and doxycycline have 97% and 98% cure rates,
51 Alternatives include erythromycin, ofloxacin, and levofloxacin.
Other quinolones should not be used because they have not been evaluated
adequately or are not reliably effective.
associated with nongonococcal urethritis (NGU)?
In the United States, NGU is the most common STD in men.
frequent cause of NGU, representing 15% to 40% of all cases. Other agents that have
been associated with NGU include M. genitalium, T. vaginalis, HSV, and
adenovirus; however, the cause for the majority of NGU cases is unknown.
variety of pathogens and disparity among identification techniques require sound
clinical judgment and an algorithmic laboratory testing approach to accurately
identify and treat the cause. A NAAT, if available, should be performed to rule out
the presence of C. trachomatis and N. gonorrhoeae.
consistent with NGU? How does one differentiate between NGU and gonococcal urethritis?
T.K.’s presentation is typical. Compared with gonococcal urethritis, NGU
typically produces less severe and less frequent dysuria and less penile discharge.
Chlamydial urethral infection is completely asymptomatic more often than
gonococcal urethral infection. The incubation period for gonococcal urethritis is 2 to
7 days, whereas the incubation period for NGU is typically 2 to 3 weeks.
Nonetheless, NGU and gonococcal urethritis cannot be reliably differentiated
solely on the basis of symptoms and signs. If there is objective evidence of a urethral
discharge (expressed by milking the urethra), a Gram stain with ≥2 WBCs per oil
immersion field in the urethral secretion, positive leukocyte esterase test
demonstrating 10 WBCs per high-power field, the diagnosis of NGU is made by
excluding the presence of N. gonorrhoeae by Gram stain and/or culture.
CASE 72-5, QUESTION 3: How should T.K. be treated?
If C. trachomatis cannot be ruled out, therapy with azithromycin 1 g PO for one
dose or doxycycline 100 mg PO twice daily for 7 days should be ordered. Compared
to doxycycline, M. genitalium responds better to azithromycin as doxycycline does
not effectively eradicate M. genitalium.
2 Azithromycin also has the advantage of a
single-dose regimen, which may aid in patient compliance. Erythromycin base 500
mg PO 4 times a day or erythromycin ethylsuccinate 800 mg PO 4 times a day for 7
days are alternative CDC-approved regimens. Additionally, ofloxacin 300 mg PO
twice daily or levofloxacin 500 mg PO every day for 7 days are other alternatives,
but they offer no significant advantages compared with the previously mentioned
agents, may not treat U. urealyticum adequately, and are significantly more
54 Ciprofloxacin should be avoided because treatment failures have been
55 Patient counseling should emphasize the need for abstinence from sexual
intercourse at least until the prescribed course of therapy has been completed (or 7
days after single-dose therapy) by the patient and his sexual partner(s).
some indication that the proportion of NGU caused by C. trachomatis is declining,
potentially being replaced by an increased proportion of U. urealyticum, which is
variably cured at 2 weeks by azithromycin (73%) and doxycycline (65%).
CASE 72-5, QUESTION 4: T.K. was treated with doxycycline 100 mg twice daily for 7 days. He remained
and a mucoid-like urethral discharge. How should T.K.’s recurrent infection be treated?
The major problem encountered in the treatment of NGU is the high rate of
recurrent infections. Men receiving treatment should follow-up if symptoms persist
or recur after completion of therapy. Approximately 20% to 60% of patients
experience recurrent or persistent urethritis within 1 to 2 weeks after treatment.
rate of recurrence is highest in patients with idiopathic urethritis, that is, those not
infected with C. trachomatis or U. urealyticum. Recurrence suggests reexposure to an
untreated partner, whereas persistent urethritis (without improvement during therapy)
suggests the presence of other organisms, including M. genitalium, U. urealyticum, or
59 NGU that persists or recurs should be retreated with the initial
regimen if the patient was not compliant or the sexual partner was not treated. For
patients with persistent symptoms, who were compliant with the initial regimen and
were not reexposed, the CDC recommends using a single 1 g dose of azithromycin if
not used for the initial episode, or moxifloxacin 400 mg PO daily for 7 days if the
patient has failed azithromycin.
Men with acute epididymitis often have chlamydial or gonococcal infection,
particularly if they are younger than 35 years of age or have a urethral discharge.
Escherichia coli and Pseudomonas species are common pathogens in homosexual
men. In older men, sexually transmitted epididymitis is less common and is more
commonly caused by urinary tract instrumentation, surgery, systemic disease, or
If testicular tenderness is present with urethritis, and the
clinical impression is consistent with epididymitis caused by Chlamydia or
gonorrhea, the CDC recommend a single dose of ceftriaxone 250 mg IM plus
doxycycline 100 mg PO twice for 10 days. For acute epididymitis caused by enteric
organisms or with a negative gonococcal culture or NAAT, ofloxacin 300 mg PO
twice daily or levofloxacin 500 mg PO once daily for 10 days may be used.
men who practice insertive anal sex, where the most likely cause of acute
epididymitis is caused by Chlamydia, gonorrhea, and enteric organisms, the CDC
recommends ceftriaxone 250 mg IM in a single dose plus levofloxacin 500 mg PO
daily or ofloxacin 300 mg PO BID for 10 days.
In the absence of cultures for Chlamydia, empirical treatment against chlamydia of
women who are sexual partners of men with NGU is recommended. Many partners
are asymptomatic but from 30% to 70% are culture positive if tested. A.C. should be
examined carefully for mucopurulent cervicitis and salpingitis. Although many
women with chlamydial infection of the cervix are asymptomatic, up to one-quarter
have evidence of mucopurulent discharge.
60 A Gram stain of appropriately collected
mucopurulent endocervical discharge from patients with Chlamydia infection shows
Regardless of findings, treatment should be initiated with the same azithromycin or
doxycycline regimen used for NGU. However, if A.C. is pregnant, tetracyclines and
fluoroquinolones should be avoided. Azithromycin 1 g PO as a single dose or
amoxicillin 500 mg PO 3 times a day for 7 days could be used instead. Alternatively,
either erythromycin base 500 mg PO 4 times a day for 7 days, erythromycin base 250
mg PO 4 times a day for 14 days, erythromycin ethylsuccinate 800 mg PO 4 times a
day for 7 days, or erythromycin ethylsuccinate 400 mg PO 4 times a day for 14 days
2 Erythromycin estolate should be avoided in pregnancy because of the
increased risk of hepatotoxicity. Azithromycin is safe and effective during
62 High rates of GI side effects limit the use of erythromycin. In pregnant
women, a repeat NAAT is recommended 3 weeks after completion of therapy to
2 Coinfection with Chlamydia is common in heterosexual men
and women with gonorrhea. Therefore, drug regimens effective against both
organisms are recommended in patients with gonorrhea to prevent postgonococcal
chlamydial morbidity (epididymitis, mucopurulent cervicitis, salpingitis) and to
reduce the genital reservoir of C. trachomatis.
ETIOLOGY AND SIGNS AND SYMPTOMS
manifestations in S.F. are consistent with LGV?
LGV or Nicolas–Favre disease has historically been considered a rare disease in
the United States and other developed nations; however, outbreaks have been
recently reported in The Netherlands and Great Britain as well as in the United States
in New York, Texas, and San Francisco.
64 Since 2003, the number of cases of
LGV, especially proctocolitis, in MSM in developed countries has been
66 The cause of LGV is usually C. trachomatis serovars L1, L2, or L3,
which are different from those serovars responsible for chlamydia urethritis.
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