CASE 72-8, QUESTION 2: N.W. was treated with an IM injection of 2.4 million-units of benzathine
rash. She was tachypneic, but normotensive. What is this reaction? How should N.W. be managed?
N.W. has developed the Jarisch–Herxheimer reaction (JHR), a usually benign,
self-limited complication of antitreponemal antibiotic therapy that develops within
hours after treatment of early syphilis.
2 The cause of JHR is not well understood, but
it is probably related to the release of cytokines.
97 Clinical manifestations include
fever, chills, myalgias, headache, tachycardia, and hypotension. The pathogenesis of
the syndrome is uncertain, but the reaction should not be interpreted as an allergic
reaction to penicillin. It typically begins within the first 24 hours after antibiotic
administration and normally subsides spontaneously, generally subsiding even while
98 Notably, JHR can occur after administration of many
antimicrobials and is not exclusive to penicillins, nor is it exclusive to syphilis
treatment, occurring in other spirochetal diseases, such as Lyme disease and
99 Usually self-limiting in nonpregnant patients, the primary risk of
this reaction in pregnant women is miscarriage, premature labor, or fetal distress.
Pregnant women should seek medical attention if contractions or a change in fetal
movements are noted. Close monitoring of JHR should be observed for patients with
ophthalmic or neurologic syphilis. For these patients, prednisolone 10 to 20 mg 3
times a day for 3 days given 24 hours before syphilis treatment may prevent fever,
but it will not control local inflammation.
86 Tumor necrosis factor-α has been
demonstrated to have some success in the prevention of JHR in spirochete disease.
Although there is no proven effective preventive therapy, some experts still
recommend antipyretics, hydration, and patient education; antibiotic therapy should
CASE 72-8, QUESTION 3: How should N.W.’s baby be treated if a diagnosis of congenital syphilis is
Infants born to mothers who have been treated for syphilis during pregnancy should
be carefully examined at birth with a quantitative nontreponemal serologic test. If
tests are reactive, the infant should be followed and have serologic testing every 2 to
3 months until nontreponemal tests are nonreactive.
2 Newborn serology is difficult to
interpret because of transplacental transfer of nontreponemal and treponemal
immunoglobulin G to the infant. Treatment decisions are largely based on evidence of
syphilis in the mother, adequacy of maternal treatment, comparison of maternal and
neonatal nontreponemal serology, and/or presence of clinical or laboratory evidence
of syphilis in the neonate. In addition, infants should be treated at birth, even if they
are asymptomatic, when maternal treatment is unknown or inadequate, or when infant
follow-up cannot be guaranteed. In most cases, a CSF examination should be
performed before treatment is begun to rule out neurosyphilis.
Chancroid or soft chancre is a painful genital ulcer disease that is often associated
the United States has steadily declined. In 2013, 10 cases of chancroid were reported
in the United States, down from 28 cases in 2009.
4 Chancroid and other genital ulcers
have also been implicated in the acquisition and transmission of HIV.
QUESTION 1: T.G., a 31-year-old uncircumcised sexually active male, presents to the STD clinic with
signs or symptoms consistent with chancroid? What diagnostic procedures are necessary?
Uncircumcised men, as well as circumcised men, may have an increased risk of
chancroid infection and may not respond to therapy. In fact, evidence suggests
circumcision is protective against nearly all STDs, including HIV, as well as
protecting women against T. vaginalis and BV.
2 A painful genital ulcer appears 3 to
10 days after exposure and begins as a tender, red papule that becomes pustular and
ulcerates within 2 days. Chancroid can be suspected if all of the following criteria
are met: (1) one or more painful genital ulcers present, (2) regional
lymphadenopathy, (3) no evidence of T. pallidum by dark-field examination, and (4)
a negative HSV PCR test or HSV culture. As illustrated by T.G., the ulcer may be
covered by a grayish or yellow exudate. A Gram stain can be misleading because of
the polymicrobic nature of the ulcer and culture and because isolation of H. ducreyi
is difficult, requiring specialized specimen collection and growth media.
CASE 72-9, QUESTION 2: How should T.G.’s chancroid be treated?
Most strains of H. ducreyi produce a TEM-type β-lactamase, and many strains are
resistant to the antimicrobials that traditionally were used to treat chancroid, such as
sulfonamides and tetracycline.
103 Currently recommended CDC treatment regimens
include azithromycin 1 g PO for 1 dose, ceftriaxone 250 mg IM once, ciprofloxacin
500 mg PO twice a day for 3 days, or erythromycin base 500 mg PO 3 times a day for
7 days. Ciprofloxacin is contraindicated in pregnant and lactating women. Because
T.G. has a history of penicillin hypersensitivity, azithromycin as a single oral dose is
a preferred treatment regimen. Treatment may not be as effective for patients who are
coinfected with HIV or who are uncircumcised; therefore, HIV testing should occur
at the time of chancroid diagnosis and if negative, should be repeated 3 months after
the diagnosis. Follow-up should occur 3 to 7 days after treatment is initiated.
Depending on the size of the ulcer, the time required until complete recovery will
vary; larger ulcers may require longer than 2 weeks. Because T.G. is also sexually
active, his sexual partner should be evaluated and treated if they had contact during
the 10 days prior to the onset of symptoms.
Approximately 10 million physician office visits are made annually in the United
States for women seeking evaluation and treatment of vaginitis.
refers to such nonspecific vaginal symptoms as itching, burning, irritation, and
abnormal discharge that may be caused by infection or other medical conditions. The
most common vaginal infections are BV (22%–50% of cases), vulvovaginal
candidiasis (VVC; 17%–39% of cases), and trichomoniasis (4%–35% of cases).
However, approximately 30% of cases of vaginitis remain undiagnosed.
Bacterial vaginosis (BV) is the most common genital tract infection amongst
106 While the exact prevalence of BV varies, one estimate
places it at 29.2%. In addition, many sexually active women are infected with G.
vaginalis, yet as much as 84% are asymptomatic.
107 During an episode of BV, the
normal vaginal lactobacillus flora is replaced by Mobiluncus species, Prevotella
species, Ureaplasma species, Mycoplasma species, and increased numbers of G.
vaginalis and is associated with an increased, malodorous vaginal discharge.
The evidence for definitive risk factors in BV is inconclusive. Multiple sexual
partners, a new sexual partner, douching, lack of condom use, and decreased
concentrations of vaginal lactobacilli have been associated with BV. Non-sexually
active women are rarely affected.
In addition, studies among women who generally
have sex with other women show evidence for sexual transmission.
treatment of male sexual partners is not recommended because a woman’s response
to therapy or her likelihood of relapse or recurrence is not impacted by treatment of
SIGNS, SYMPTOMS, AND DIAGNOSIS
QUESTION 1: H.H. is a 24-year-old, sexually active woman with a 1-week history of moderate vaginal
and a characteristic fishy odor was noted when the discharge was mixed with 10% potassium hydroxide
(KOH). Does H.H. have signs and symptoms consistent with BV? What diagnostic tests are required?
H.H.’s signs and symptoms are typical of BV. The clinical diagnosis can be
confirmed by a vaginal Gram stain that shows overgrowth of the vagina with G.
vaginalis and other organisms as noted earlier. A 10% KOH solution mixed with the
vaginal secretions yields a transient fishy odor because of the increased production
of biogenic diamines (positive amine test). A wet preparation of the specimen
reveals “clue cells” (exfoliated vaginal epithelial cells sometimes with adherent
coccobacillary pathogens), vaginal pH greater than 4.5, and the characteristic KOH
If there are many white cells, other infections (e.g., T. vaginalis)
should be suspected. Self-diagnosis is correct only about 3% to 4% of the time
because most women attribute symptoms to poor hygiene.
CASE 72-10, QUESTION 2: How should H.H. be treated?
metronidazole gel 0.75% intravaginally daily for 5 days, or clindamycin cream 2%
intravaginally at bedtime for 7 days.
2 The FDA has approved metronidazole extended
release 750 mg once daily for 7 days and a single dose of clindamycin intravaginal
cream for the treatment of BV; however, limited data have been published comparing
these regimens to established therapies. Alternatively, the CDC recommends either
tinidazole 2 g PO every day for 2 days, tinidazole 1 g PO every day for 5 days,
clindamycin 300 mg PO 2 times a day for 7 days, or clindamycin ovules 100 mg
intravaginally once at bedtime for 3 days.
2 Patients should be instructed to avoid
consuming alcohol during treatment with metronidazole and for 72 hours afterward to
avoid disulfiram-like reactions. Additionally, clindamycin cream is oil based and
may weaken latex condoms or diaphragms. Alternative products include probiotics
which have been evaluated in non-pregnant women and have shown to improve cure
rates and reduce the reoccurrence of BV, although more studies are needed to
establish their role in treatment.
BV has been associated with preterm labor and premature delivery and treatment
is recommended for all symptomatic women. The CDC recommends metronidazole
250 mg PO 3 times daily for 7 days or 500 mg PO twice a day for 7 days, or
clindamycin 300 mg PO twice daily for 7 days. Teratogenic data suggest that
metronidazole is not harmful to the fetus. More recent data suggest that the use of
intravaginal clindamycin cream is also safe to use for pregnant women.
Candida albicans is the causative organism of VVC in 80% to 92% of cases, with
Candida glabrata and Candida tropicalis accounting for most of the remaining
114 The latter organisms have been identified increasingly as the
causative agents of VVC during the past two decades. Approximately 75% of women
will experience at least one episode of VVC during their reproductive years and 40%
to 45% will have two or more episodes within their lifetime.
women who have VVC have recurrent candidal episodes (defined as four or more
year). Vulvovaginal candidiasis is not usually described as an STD because celibate
women may also experience it; however, the incidence of VVC increases when
114 Because of this, VVC is often diagnosed during
evaluation for a suspected STD when women present with vaginal symptoms.
The pharmacist should ask L.L. if this is her first episode of vaginitis or whether
she has experienced similar symptoms previously that have been diagnosed as a
vaginal yeast infection and treated by a physician. The nonprescription antifungal
agents are indicated for the treatment of VVC in women who previously were
diagnosed and treated by their physician. Additional questions that should be asked
by the pharmacist include current symptoms, whether they are pregnant or not, other
current medical conditions or medications, and allergies. Patients should be referred
to a physician if any of the following are present: first episode of VVC, has had more
than three episodes of VVC within the past 12 months, last episode was less than 2
months ago, is pregnant, is younger than 12, fever, lower abdominal, back, or
shoulder pain, severe symptoms, or has a malodorous vaginal discharge.
CASE 72-11, QUESTION 2: L.L. has experienced two episodes of vaginal yeast infections, with the most
L.L. exhibit that are consistent with VVC? What are the other common manifestations?
L.L. exhibits signs and symptoms associated with VVC (i.e., vulvar and vaginal
pruritus, vaginal soreness, vulvar burning, dyspareunia, and a thick, white vaginal
discharge that appears to be curd-like). Women may also have vaginal discharge
which is usually described as nonodorous, highly viscous, and white in color that
may vary in consistency from curd-like to watery. Vulvar erythema may also be
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