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521
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522 S ECTION F OUR • Infection
T A B L E 3 1 – 1 T A B L E 3 1 – 3
Classification of Group A Streptococcal Diagnostic Criteria for Streptococcal Toxic
Infections Shock Syndrome
1. Streptococcal toxic shock syndrome (streptococcal TSS) I. Isolation of Streptococcus pyogenes
2. Other invasive infections (isolation of Streptococcus pyogenes from A. From a normally sterile site
a normally sterile site in patients not fulfilling criteria from B. From a nonsterile site (throat, sputum, vagina, superficial skin
streptococcal TSS) lesion)
a. Bacteremia with no identifiable focus II. Clinical evidence of severity
b. Focal infection with or without bacteremia (meningitis, A. Hypotension (systolic blood pressure ≤ 90 mm Hg in adults or
pneumonia, peritonitis, puerperal sepsis, osteomyelitis, septic ≤ 5th percentile for age in children) and
arthritis, necrotizing fasciitis, surgical wound infections, B. Two or more of the following:
erysipelas, cellulitis) 1. Renal impairment (serum creatinine ≥ 2.0 mg/dL or a twofold
3. Scarlet fever elevation over baseline level in patients with preexisting renal
4. Noninvasive infections (recovery of S. pyogenes from a nonsterile impairment)
site) 2. Coagulopathy (platelets ≤ 100 × 106/L or disseminated
a. Mucous membranes (pharyngitis, tonsillitis, otitis media, intravascular coagulation)
sinusitis, vaginitis) 3. Liver involvement (AST, ALT, or total bilirubin ≥ two times
b. Cutaneous (impetigo) upper limits of normal)
5. Nonsuppurative sequelae (specific clinical findings with evidence of 4. Adult respiratory distress syndrome
a recent group A streptococcal infection) 5. Generalized erythematous macular rash
a. Acute rheumatic fever 6. Soft tissue necrosis (necrotizing fasciitis, myositis, or
b. Acute glomerulonephritis gangrene)
Adapted from The Working Group on Severe Streptococcal Infections: Defining ALT, alanine aminotransferase; AST, aspartate aminotransferase.
the group A streptococcal toxic shock syndrome. JAMA 1993;269:390– Adapted from The Working Group on Severe Streptococcal Infections: Defining
391. the group A streptococcal toxic shock syndrome. JAMA 1993;269:
390–391.
T A B L E 3 1 – 2 Diagnosis
Diseases Seen among Patients with Postpartum GASs can be readily recovered from most patients with
Group A Streptococcus Infection evidence of GAS disease. GASs are catalase-negative gram-
INFECTION NUMBER OF PATIENTS (N = 87) positive cocci that are β-hemolytic on blood agar. The colo-
nies may appear as highly mucoid to nonmucoid, and the
Bacteremia without focus 40 (46%) organisms are usually 1 to 2 mm in diameter. Although cul-
Endometritis 24 (28%) tures may be helpful in confirming the diagnosis of GAS
Peritonitis 7 (8%) disease, they are seldom available when considering the
Septic abortion 6 (7%) initial diagnosis. GAS disease may progress rapidly, and
Cellulitis 3 (3%) therapy must be initiated before cultures are generally
Septic arthritis 3 (3%) available.
Necrotizing fasciitis 3 (3%)
Therefore, the diagnosis of GAS disease depends upon a
high index of suspicion. Fever is the most common present-
Streptococcal toxic shock syndrome 3 (3%)
ing sign, and 20% of patients have a flulike syndrome with
Chorioamnionitis 3 (3%)
fever, chills, myalgia, nausea, vomiting, and diarrhea.13 Con-
Pneumonia 1 (1%) fusion or altered mental status is present in over one half of
Other 3 (3%) patients. Renal dysfunction occurs in 80% of patients and
Adapted from Chuang I, Van Beneden C, Beall B, Schuchat A: Population-based
may precede hypotension or shock. The presence of hema-
surveillance for postpartum invasive group A streptococcus infections, globinuria or an elevated serum creatinine is evidence of
1995–2000. Clin Infect Dis 2002;35:665–670. renal involvement. Hemoconcentration, as a result of a fluid
shift to the extravascular compartment, and leukocytosis
(often > 20,000/mm3), with a predominance of immature
Neonatal invasive GAS has also been reported and has a neutrophils, are common. Respiratory failure and adult respi-
case fatality rate of up to 30%.9–11 Although the neonate may ratory distress syndrome occur in approximately 50% of
be colonized following horizontal transmission within the patients but usually develop after the onset of clinically
nursery, vertical transmission from a colonized mother has recognized shock. Criteria for the diagnosis of STSS are
also been demonstrated.10,12 Furthermore, 50% of neonatal outlined in Table 31–3.
cases of invasive GAS disease occur within the first week of Eighty percent of patients have evidence of soft tissue
life, suggesting that vertical transmission from a colonized infection characterized by induration and erythema, which
parturient may be the most important route of infection. The progress to necrotizing fasciitis in 70% of cases.13 The hall-
most frequent manifestation of neonatal GAS disease is mark of these soft tissue infections is the abrupt onset of
omphalitis, but cellulitis, meningitis, sepsis, and fasciitis may severe pain, which usually precedes physical findings or is
also occur. Fortunately, neonatal GAS disease is rare, with out of proportion to physical findings. Any patient suspected
an estimated incidence of 1 in 18,000 births. of having GAS-associated necrotizing fasciitis must have the
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C HAPTER 31 • Other Infectious Conditions 523
diagnosis confirmed by immediate wound exploration and Broad-spectrum parenteral antibiotics should be admin-
débridement. A purulent discharge is usually not present, istered promptly. Penicillin G (200,000–400,000 U/kg/
and a limited wound inspection may fail to confirm the day) is the drug of choice for GAS invasive infections.
diagnosis. When the wound is opened, a thin, watery, non- However, studies in mice have demonstrated that even a
malodorous discharge is frequently present. The diagnosis short delay of 2 hours after initiation of infection dramati-
of necrotizing fasciitis can be easily confirmed by the blood- cally reduces the efficacy of penicillin G.17 Some studies
less blunt dissection of the superficial fascia and by patho- indicate that clindamycin may be more efficacious than
logic frozen section. penicillin when therapy is delayed. In an experimental
In summary, the diagnosis of GAS disease should be con- model with mice, survival was 70% even when initiated 16
sidered in any patient with the sudden onset of hypotension hours after GAS infection.17 Several potential advantages
and shock, the abrupt onset of severe pain in a wound, or to clindamycin therapy (900 mg IV q8h) have been identi-
systemic signs and symptoms such as confusion, renal fied.7 First, in contrast to penicillins, clindamycin is not
impairment, or respiratory distress in a patient with a wound affected by bacterial inoculum size or rate of growth.
or episiotomy infection. Aggressive intravenous fluid resus- Second, clindamycin suppresses the synthesis of bacterial
citation, antibiotic therapy, and wound débridement are toxins. Third, clindamycin facilitates phagocytosis of S.
necessary in these patients. pyogenes by inhibition of M protein synthesis. Fourth,
clindamycin has a longer postantibiotic effect than penicil-
lin. Last, clindamycin suppresses lipopolysaccharide-
Management Options induced monocyte synthesis of tumor necrosis factor-alpha
(TNF-α), a cytokine that contributes to hypotension and
Prepregnancy shock. However, a small proportion of GAS infections are
No current evidence suggests that the identification of GAS resistant to clindamycin, and clindamycin should not be
carriers prior to pregnancy is predictive of subsequent used alone until the organism is demonstrated to be sus-
pregnancy outcome or effective in reducing puerperal ceptible by susceptibility testing. Therefore, initial therapy
infectious morbidity. Therefore, prepregnancy screening is usually includes a combination of both penicillin G and
not recommended. clindamycin.
Some data also indicate that intravenous immunoglobu-
Prenatal lin (IVIG) (1–2 g/kg given once) may be a useful adjunct
Women may be identified as being GAS carriers as a result to antibiotic therapy in the treatment of STSS. Commer-
of routine screening for group B streptococcus (GBS) near cial preparations of IVIG have been shown to contain
the end of pregnancy. In one study, 0.03% of women neutralizing antibodies to several streptococcal virulence
screened at 35 to 37 weeks’ gestation were found to have factors.18 Recently, investigators reported a significant
vaginal colonization with GAS.14 At present, there are not reduction in mortality rate among patients with GAS
sufficient data to make a recommendation regarding man- disease treated with IVIG when compared with a historical
agement of asymptomatic carriers. However, there are pub- cohort.
lished case reports of women identified as carriers during Thus, the optimal treatment for invasive GAS disease
pregnancy who then developed GAS sepsis after delivery.15 includes a high index of suspicion, aggressive fluid resuscita-
A case of puerperal sepsis in a woman with a strain of GAS tion and hemodynamic support, surgical exploration and
identical to that identified in her husband’s throat swab has aggressive débridement, parenteral antibiotics including
also been reported.16 penicillin G and clindamycin, and possibly IVIG.
A high index of suspicion is necessary for the early diag-
nosis of GAS infection. Unfortunately, diagnosis may be Labor and Delivery
difficult in the early stages of GAS infection, and delays in GAS may be associated with intra-amniotic infection and
therapy may be associated with increased morbidity and with stillbirth. However, most patients with invasive GAS
mortality rates. Many patients die within 24 to 48 hours of disease usually present in the postpartum period, frequently
infection.17 In general, treatment must be directed at hemo- within the first 24 to 48 hours. Treatment should follow the
dynamic stabilization with intravenous fluids and vasopres- general guidelines provided earlier.
sors, antibiotic therapy, and in the case of soft tissue
infections, surgical exploration and aggressive débridement Postnatal
of involved tissues. Massive amounts of intravenous crystal- There are no current recommendations for screening for or
loids, in the range of 10 to 20 L/day, are often necessary to treating asymptomatic parturients colonized with GAS.
maintain blood pressure and tissue perfusion. Vasopressors However, careful attention should be given to any parturient
such as dopamine are also frequently required. In soft tissue with the sudden onset of systemic signs such as hypotension
GAS infections such as necrotizing fasciitis, antibiotic or shock or to parturients with severe pain out of proportion
therapy alone, without surgical débridement, usually results of physical findings or rapidly progressive soft tissue infec-
in maternal death. Intraoperative Gram stain and histologic tions, as noted earlier. Although these findings, which are
frozen section may be necessary to fully delineate the extent consistent with necrotizing fasciitis, usually suggest a
of involved tissues. Hyperbaric oxygen therapy has no role polymicrobial infection, GAS should be considered in the
in the treatment of necrotizing fasciitis but might be a useful diagnosis, and broad-spectrum antibiotics including peni-
adjunct in delineating necrotic tissue that must be surgically cillin and clindamycin should be utilized in the initial
débrided. management.
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524 S ECTION F OUR • Infection
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C HAPTER 31 • Other Infectious Conditions 525
cervix in 10% to 30% of pregnant women at some point intrapartum, postpartum, and occasionally prenatal infec-
during gestation.24 The colonization may be transient, tions. Data from an early report suggest puerperal septice-
chronic, or intermittent, and the rate of colonization does mia due to GBS occurs with an incidence of approximately
not vary with gestational age. Women with GBS coloniza- 1 to 2 per 1000 deliveries and accounts for up to 15% of
tion in one pregnancy are at increased risk, relative to positive blood cultures from postpartum patients.28 Postpar-
women who are negative in the initial pregnancy, for colo- tum endometritis is reported to be more frequently observed
nization in a subsequent pregnancy.25 There is evidence that among GBS-colonized parturients than among noncolo-
the gastrointestinal tract is the major primary reservoir and nized parturients. GBS is also associated with clinical intra-
that vaginal or cervical contamination and colonization amniotic infection and is a frequent isolate from amniotic
occur from a gastrointestinal source. The frequency of GBS fluid of patients with intra-amniotic infection. Finally, GBS
isolation increases as one proceeds from the cervix to the has been isolated from the urine of pregnant women, with
introitus, and GBS can be recovered twice as frequently from or without symptoms of urinary tract infection. Untreated
rectal cultures as from vaginal cultures. GBSs can also be antepartum GBS bacteriuria has been associated with intra-
recovered from the urethra of 45% to 63% of the male partum chorioamnionitis.29
consorts of female carriers, implying that sexual transmission GBS has also been associated with premature rupture of
may also occur. membranes (PROM) and with preterm delivery prior to the
Neonatal GBS colonization may occur either by vertical 32nd gestational week in some, but not all, studies.30 Previ-
transmission from a colonized mother as the neonate passes ous studies have indicated that this association may be
through the birth canal or by horizontal transmission, strongest for patients with GBS bacteriuria.31 Thomsen
including both nosocomial spread in the nursery from colo- and coworkers32 have demonstrated significant reductions in
nized personnel or other colonized neonates and acquisition PROM and preterm labor among patients with asymptom-
from community sources. Overall, 3% to 12% of all neo- atic GBS bacteriuria who were treated with penicillin.
nates are colonized with GBS in the first week of life. Forty However, antepartum antibiotic treatment to eradicate GBS
percent to 70% of neonates born to colonized mothers from patients with asymptomatic vaginal colonization
become colonized, usually with the same serotype that is without bacteriuria has not been demonstrated to alter preg-
present in the mother. In contrast, only 1% to 12% of neo- nancy outcome. Thus, a causal relationship between GBS
nates born to noncolonized mothers will become culture- colonization and prematurity remains to be established.
positive. Several additional factors may modify or enhance Since the 1970s, GBS has become a leading cause of
the risk of GBS vertical transmission. Higher neonatal trans- septicemia and meningitis during the first 3 months of life
mission rates occur when women are persistently culture- in neonates. Early surveillance data in the 1990s suggested
positive carriers or when women are heavily colonized with an incidence of 1.8 cases per 1000 live births. Two distinct
GBS as demonstrated by semiquantitative vaginal cultures.26 clinical syndromes occur among neonates with GBS infec-
The site of maternal carriage is also important; vertical trans- tions. These differ in the age at onset, pathogenesis, and
mission is more likely to occur with cervical GBS carriage outcome. The first clinical syndrome, early-onset infection,
than with rectal carriage. occurs within the first 7 days of life and represents nearly
The most important determinant of susceptibility to inva- three fourths of all cases in infants younger than 3 months.
sive infection after colonization may be maternal antibodies The mean age at onset is 20 hours of life, and 72% will
directed against the capsular polysaccharide antigens of present within the first 24 hours of life.33 A significant
GBS. Immunity to GBS is mediated by antibody-dependent portion of these infections are apparent at birth or become
phagocytosis. Mothers of infants with type III GBS invasive symptomatic within the first 90 minutes of life, indicating
disease have lower serum levels of type-specific antibodies that in utero GBS exposure and infection often occur. Early
than women giving birth to asymptomatically colonized infection attack rates were estimated at 1.5 per 1000 for all
infants. This antibody, which has some broad reactivity to live births prior to widespread use of intrapartum antibiotics.
all GBS types, is an immunoglobulin G (IgG) that readily Among offspring of maternal GBS carriers, however, the
crosses the placenta. When measured in mother-infant pairs, attack rate is much higher, ranging from 10 to 60 per 1000
an excellent correlation exists between maternal and cord live births.
antibody levels. Baker and associates27 demonstrated that Early neonatal infection is presumed to result from vertical
73% of 45 GBS-colonized mothers with healthy neonates transmission of GBS from a colonized mother. There is a
had high serum levels of type III antibody in contrast to only direct relationship between neonatal attack rates and the
19% of 32 GBS-colonized mothers whose neonates devel- size of the inoculum and number of colonized neonatal sites.
oped early-onset septicemia or meningitis (P < .001). Strain In one epidemiologic review, early-onset infection presented
virulence is also an important determinant of disease. as bacteremia (80%), pneumonia (7%), or meningitis (6%).33
Although type III strains of GBS represent approximately Eighty-three percent of cases were in term infants (≥37 wk’
one third of isolates from symptomatically colonized infants, gestation). The overall case fatality rate was approximately
they account for over 85% of the isolates from early-onset 4% but was significantly higher in preterm infants, approach-
meningitis or late-onset disease. Overall, type III strains ing 30% in infants of 33 weeks’ gestation or less.
account for more than 60% of isolates from infants with all The second type of disease (late-onset infection) occurs
varieties of invasive GBS infections. in infants after the first week of life until 3 months of age,
with a typical range of 3 to 4 weeks. The overall attack rate
is estimated to be 0.5 cases per 1000 live births, and these
Maternal and Fetal Risks cases represent 28% of infections in infants younger than 3
Although most research has focused on GBS neonatal infec- months.33 In contrast to early-onset infection, nosocomial
tion, GBS is also an important pathogen for maternal transmission may be as important as vertical transmission,
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526 S ECTION F OUR • Infection
although it is believed that some infants are colonized at assays that demonstrate excellent sensitivity and specificity
birth, with subsequent development of invasive disease. The compared with traditional culture methods, but these assays
serotype distribution of strains recovered from late-onset await further testing to determine the feasibility of wide-
infection does not reflect the serotypes present in the mater- spread application.43–45 A cost-benefit analysis showed that
nal genital tract; over 90% of late-onset infection is caused the use of a rapid PCR test resulted in fewer courses of
by type III GBS. Late-onset disease also presents most com- maternal antibiotics, fewer perinatal GBS infections, and
monly as bacteremia (63%), but may appear as meningitis fewer infant deaths compared with culture.46 However, only
(24%, relative risk [RR] 4.3 vs. early-onset disease; P < .001) culture techniques currently allow for antibiotic sensitivity
and may demonstrate other sites of infection, such as septic profiling of positive cultures, which is particularly important
arthritis or osteomyelitis. The overall case fatality rate for in cases of maternal penicillin hypersensitivity.
late-onset disease is 2.8%.33 Approximately 50% of menin-
gitis survivors will have neurologic sequelae, including corti- Management Options
cal blindness, diabetes insipidus, deafness or other cranial
nerve deficits, and spasticity. Prepregnancy
No current evidence suggests that the identification of GBS
carrier status prior to pregnancy is predictive of subsequent
Diagnosis pregnancy outcome. Similarly, treatment of asymptomatic
The recommended technique for collecting specimens for women found to be colonized with GBS prior to pregnancy
culture of GBS in pregnant women involves obtaining a does not impart any recognized benefit, with the possible
combined vaginal-rectal swab. Although some studies have exception of women with asymptomatic bacteriuria.
shown that the GBS detection rate is not significantly dif-
ferent when comparing vaginal-rectal specimens with vagi- Prenatal, Labor, and Delivery
nal-perianal specimens,34,35 the current standard of care is GBS rarely causes maternal symptoms in the prenatal period,
still to obtain a combined vaginal-rectal swab. A speculum but may cause symptoms of urinary tract infection. However,
is not necessary, and there is no difference in detection rates GBS bacteriuria (whether symptomatic or not) provides a
or accuracy if the culture is collected by the patient or the significant risk factor for neonatal disease, as previously
health care provider.36 mentioned. When detected, GBS bacteriuria should be
GBS can be easily grown on selective or nonselective treated according to current standard of care for urinary tract
media. Most GBS colonies appear on blood plates as small, infections during pregnancy. Pregnant women with docu-
1- to 2-mm, gray-white colonies surrounded by a zone of mented GBS bacteriuria at any time during their prenatal
β-hemolysis, although 2% of strains are nonhemolytic. Pre- course do not require routine screening cultures and should
liminary identification and distinction of GBS from other receive intrapartum antibiotics, which are discussed in
streptococci is based on biochemical reactions including further detail later.
resistance to bacitracin, hydrolysis of sodium hippurate, Although the attack rate for neonatal GBS infection is
and the production of a soluble hemolysin that acts syner- low, a variety of prevention strategies have been advocated
gistically with B-lysin of Staphylococcus aureus to produce because of the high mortality and morbidity rates seen in
hemolysis (CAMP [Christie-Atkins-Munch-Petersen] test). neonatal GBS disease. These strategies have involved che-
Although GBS can be recovered after overnight growth on moprophylaxis, aimed at eradicating the organism from the
nonselective media, such as blood agar, the use of a selective mother or the neonate, or immunoprophylaxis, aimed at
broth medium such as Todd-Hewitt broth or Lim broth inducing humoral immunity.
greatly enhances the isolation rate of GBS from any culture Antibiotic chemoprophylaxis has been advocated for the
site. pregnant patient in either the antepartum or the intrapartum
A major limitation of cultures is the length of time neces- period or for the neonate in the immediate neonatal period.
sary for growth and identification. Therefore, research has Attempts to eradicate GBS colonization with antepartum
been focused on developing a more rapid screening test that treatment have been unsuccessful, and early neonatal pro-
could be used at the time of labor and delivery to identify phylaxis is also frequently unsuccessful because many neo-
colonized women. A number of rapid screening tests have nates are already septic at birth as a result of in utero
been developed to directly detect GBS in either body fluids infection.47 Initial chemoprophylactic prevention strategies
or cervical-vaginal secretions. These culture-independent released in the 1990s focused upon selective intrapartum
tests include Gram stain, latex particle agglutination treatment based on either the presence of risk factors associ-
(LPA), optical immunoassay, enzyme immunoassay, DNA ated with neonatal infection, the maternal genital tract colo-
hybridization, and polymerase chain reaction (PCR). A nization, or both.
large number of studies have evaluated the ability of these Major risk factors for neonatal early-onset GBS disease
indirect tests to rapidly detect GBS colonization of the include low birth weight (<2500 g), premature delivery
maternal lower genital tract. Such identification is important (<37 wk’ gestation), prolonged duration of rupture of mem-
to interrupt maternal-neonatal vertical transmission that branes (≥18 hr), and intrapartum fever (≥38.0°C). Boyer and
leads to early-onset neonatal disease. Initial results were colleagues47 have demonstrated that 74% of neonates with
encouraging,37,38 although subsequent studies have demon- early-onset infection and 94% of those infections with a fatal
strated that these tests do not always perform well.39,40 PCR outcome occur among those neonates with one or more of
tests appear to have the most promise and the best test these risk factors. Additional risk factors include having pre-
performance characteristics relative to culture.41–43 Recent viously had a neonate with invasive GBS disease and mater-
studies from the United States and Canada have used PCR nal GBS bacteriuria during the current pregnancy. A study
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C HAPTER 31 • Other Infectious Conditions 527
in 1985 documented that the overall attack rate for early- 18.3% of pregnancies were estimated to merit chemopro-
onset neonatal GBS disease increased from the then-observed phylaxis and 68.8% of early-onset neonatal disease would
3.0 per 1000 births in the total population to 8.4 per 1000 be potentially prevented.21
births among those pregnancies in which risk factors were The impact of implementing these guidelines has been
present.48 The attack rate rose even more dramatically to studied extensively in the period following their initial rec-
40.8 per 1000 births if risk factors were present and the ommendation. In the surveillance areas studied, the inci-
mother was colonized with GBS. dence of early-onset disease declined from 1.7 per 1000 in
Several studies utilizing the presence of risk factors, 1993 to 0.6 per 1000 in 1998, a 65% reduction, with the
maternal colonization status, or both, as a determinant for steepest decline occurring in 1996 following the initial
prophylaxis have documented the efficacy of intrapartum release of consensus guidelines from the CDC. Schrag and
chemoprophylaxis in reducing neonatal early-onset GBS associates57 published the first comprehensive study directly
disease.49–55 A meta-analysis of these studies demonstrated a comparing the two management strategies and found that
30-fold reduction in early-onset disease with intrapartum the universal screening-based approach was greater than
chemoprophylaxis.56 The two alternative approaches to 50% more effective in preventing perinatal GBS disease.
intrapartum chemoprophylaxis were proposed in the United This result was felt to stem from two main factors. First, the
States by the CDC in 199621 and have been endorsed by screening-based approach identified mothers who were
both ACOG20 and AAP.22 The first approach is based upon GBS-positive but did not exhibit risk factors during preg-
universal screening for maternal GBS colonization at 35 to nancy or labor, a group representing 18% of all parturients
37 weeks’ gestation. Cultures remote from term might not during the study period. Second, women identified as being
be accurate and should not be used. Intrapartum chemopro- GBS-positive were more likely to receive intrapartum anti-
phylaxis is offered to all pregnant women identified as GBS biotics than women who qualified on the basis of risk factors
carriers. In addition, intrapartum chemoprophylaxis is (89% vs. 61%, P < .001), indicating improved compliance
offered to women with a previous neonate with GBS infec- with the guidelines utilizing the screening-based approach.
tion, GBS bacteriuria during the current pregnancy, or deliv- In this study, similar numbers of patients (24%) in each
ering prior to 37 weeks’ gestation, regardless of maternal group received intrapartum prophylaxis, negating previous
colonization status. Women with an unknown carrier status concerns that the screening-based approach would result in
are offered prophylaxis in the event of an intrapartum fever a significant increase in the use of antibiotics and potential
of 38.0°C or higher or rupture of membranes at 18 hours or contribution to antibiotic resistance. Also, other studies have
before. It was estimated that this screening-based approach suggested that the increased cost of performing routine cul-
would result in intrapartum chemoprophylaxis of 26.7% of tures on all eligible pregnant women would be offset by the
all deliveries and prevent 86% of early-onset neonatal GBS impact of disease prevention. This idea led to the release of
disease (Table 31–4).21 new guidelines by the CDC in 2002,23 recommending a
An alternative prophylactic strategy, also initially universal screening-based approach (Fig. 31–1). The risk-
endorsed by the CDC, is based upon offering intrapartum based approach should be used only for women who arrive
chemoprophylaxis only in the presence of risk factors. In in labor with no documented culture results. In addition, a
this risk-factor approach, antepartum cultures are not new algorithm was provided for the management of women
obtained, and prophylaxis is offered only to those women with preterm delivery, summarized in Figure 31–2. An evalu-
with delivery prior to 37 weeks’ gestation, rupture of mem- ation of the universal antenatal screening approach for GBS
branes for greater than 18 hours, an intrapartum fever at or was recently published, highlighting the efficacy achieved
above 38.0°C, a previously infected neonate, or with GBS and areas in which further improvements in management
bacteriuria in the current pregnancy. With this approach, might result in the additional reductions in neonatal disease.58
T A B L E 3 1 – 4
Intrapartum Chemoprophylaxis Trials for the Prevention of Neonatal Early-onset Group B
Streptococcus Disease
EARLY-ONSET DISEASE
STUDY CASE SELECTION COMPARISON GROUP ICP NO ICP P VALUE
49
Allardice I Nonrandom 0/57 9/136 .06
Boyer50 PC Random 0/85 5/79 .02
Morales51 PC Random 0/135 3/128 .2
Morales52 I Nonrandom 0/36 13/48 .002
Tuppurainen53 PC Random 1/88 10/111 .03
Matorras54 I Random 0/60 3/65 .14
Garland55 PC Nonrandom 16/30,197 27/26,915 .04
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528 S ECTION F OUR • Infection
FIGURE 31–1
Vaginal and rectal GBS screening cultures at 35–37 weeks’ gestation
Indications for intrapartum antibiotic prophylaxis to prevent
for ALL pregnant women (unless patient had GBS bacteriuria during pregnancy
prenatal group B streptococcus (GBS) disease under a
or a previous infant with invasive GBS disease)
universal prenatal screening strategy based on combined
vaginal and rectal cultures collected at 35 to 37 weeks’
gestation from all pregnant women. (From Centers for Disease
Control and Prevention [CDC]: Prevention of perinatal group B
streptococcal disease: Revised guidelines from CDC. MMWR Morb
Intrapartum prophylaxis indicated Intrapartum prophylaxis not indicated Mortal Wkly Rep 2002;51[RR-11]:1–18.)
• Previous infant with invasive • Previous pregnancy with a positive
GBS disease GBS screening culture (unless a
• GBS bacteriuria current culture was also positive during the
pregnancy current pregnancy)
• Positive GBS screening culture • Planned cesarean delivery
during current pregnancy (unless performed in the absence of labor
a planned cesarean delivery, in or membrane rupture (regardless of
the absence of labor or amniotic maternal GBS culture status)
membrane rupture, is performed) • Negative vaginal and rectal GBS
• Unknown GBS status (culture screening culture in late gestation
not done, incomplete or results during the current pregnancy,
unknown) and any of the following: regardless of intrapartum risk
Delivery at ≤37 weeks’ factors
gestation
Amniotic membrane
rupture ≥18 hours
Intrapartum temperature
≥100.4° F (≥38.0° C)
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C HAPTER 31 • Other Infectious Conditions 529
GBS, group B streptococcus; GPP, good practice point; IAP, intrapartum antibiotic prophylaxis.
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530 S ECTION F OUR • Infection
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C HAPTER 31 • Other Infectious Conditions 531
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532 S ECTION F OUR • Infection
Diagnosis T A B L E 3 1 – 5
Listeria grows well on most routine media, although the use Dietary Recommendations for Pregnant Women
of selective media may be required when cultures are
obtained from sites of heavy bacterial colonization such as Do not eat hot dogs, luncheon meats, or deli meats unless they are
the vagina or rectum. Owing to morphologic similarity, reheated until steaming hot.
Do not eat soft cheeses such as feta, Brie, Camembert, blue-veined
it may be confused with nonpathogenic diphtheroids. cheeses, and Mexican-style cheeses such as “queso blanco fresco.”
However, the organism produces a characteristic tumbling Hard cheeses, semisoft cheeses such as mozzarella, pasteurized
motion when viewed on wet preparation, allowing it to be processed cheese slices and spreads, cream cheese, and cottage
distinguished. Of the four serotypes, subtypes 1/2a, 1/2b, cheese can be safely consumed.
Do not eat refrigerated pâté or meat spreads. Canned or shelf-stable
and 4b are responsible for the vast majority of infections, pâté and meat spreads can be eaten.
and serotype analysis may be useful in epidemic settings.70 Do not eat refrigerated smoked seafood unless it is an ingredient in a
The diagnosis depends upon clinical suspicion and isola- cooked dish such as a casserole. Examples of refrigerated smoked
tion of the organism from a culture of appropriate source. In seafood include salmon, trout, whitefish, cod, tuna, and mackerel,
the large series mentioned previously, Listeria was most com- which are most often labeled as “nova-style,” “lox,” “kippered,”
“smoked,” or “jerky.” This fish is found in the refrigerated section or
monly isolated from cultures of the blood (43%), cervix/ sold at deli counters of grocery stores and delicatessens. Canned
vagina (34%), and placenta (12%). It may also be cultured fish such as salmon and tuna or shelf-stable smoked seafood may
from amniotic fluid obtained by amniocentesis performed be safely eaten.
for suspected intra-amniotic infection. Staining of amniotic Do not drink raw (unpasteurized) milk or eat foods that contain
unpasteurized milk.
fluid by meconium, especially in the preterm infant, may
increase clinical suspicion for listeriosis, because this was
observed in 12 of 23 infants in a reported series from
Australian authors.79
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C HAPTER 31 • Other Infectious Conditions 533
Listeriosis Monocytogenes
Evidence Quality and
Management Options Recommendation References
Prepregnancy
No benefit to screening. III/B 70
Treatment of documented infection depending on the site (see later). IV/C 84–86
Prenatal, Labor, and Delivery
Avoid unpasteurized dairy products and certain meat products (see III/B 83,84
Table 31–5)
Culture appropriate sites if listeriosis suspected (blood, CSF, cervix, —/GPP —
amniotic fluid).
Treatment IV/C 84–86
● First-line therapy: IV ampicillin 200 mg/kg/day (divided into four
doses), max = 12 g/day.
● For penicillin-sensitive patients: trimethoprim/sulfamethoxazole
(20 mg/kg/day in three or four doses).
● Other antibiotics: erythromycin, vancomycin. Note: cephalosporins
not effective.
● Duration of therapy: 10–14 days for superficial infection/
bacteremia; 14–21 days for meningitis.
Postnatal
Evaluate neonate with blood and CSF cultures. —/GPP —
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534 S ECTION F OUR • Infection
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C HAPTER 31 • Other Infectious Conditions 535
and pneumonia. Eighteen percent to 50% of exposed infants LABOR AND DELIVERY
develop conjunctivitis within the first 2 weeks of life, and See the section on “Gonorrhea.”
11% to 18% will develop pneumonia in the first 4 months
of life. POSTNATAL
The incidence of neonatal inclusion conjunctivitis can be
Diagnosis reduced by ocular prophylaxis at birth with 0.5% erythro-
The diagnosis of chlamydial infections is based upon isola- mycin ocular ointment or 1% tetracycline ointment, but not
tion of the organism, or culture-independent detection by as well by 1% silver nitrate drops. Conjunctivitis that does
immunoassay and DNA detection by PCR and serologic occur, or pneumonia, should be treated with oral erythro-
testing. Because chlamydiae are obligatory intracellular bac- mycin for 2 weeks.
teria, isolation by culture requires inoculation onto a suscep-
tible tissue culture cell line. Cell cultures are both Genital Mycoplasmas
labor-intensive and expensive and are not readily available
to most clinicians. Antigen detection kits are widely avail- Maternal and Fetal Risks
able to detect chlamydia and represent a less costly alterna- Mycoplasmas are a ubiquitous group of microorganisms that
tive to culture. More recently, detection of C. trachomatis inhabit the mucosa of the genital and respiratory tracts.
DNA from the genital tract, or from urine, by PCR or ligase They differ from bacteria in that they lack a cell wall, but
chain reaction (LCR) has been demonstrated to be greater they are susceptible to antibiotics that inhibit protein syn-
than 90% sensitive and specific for the detection of C. tra- thesis. The two most common genital mycoplasmas are
chomatis and has largely replaced cultures and antigen detec- Mycoplasma hominis and Ureaplasma urealyticum. The prevalence
tion assays. A serum microimmunofluorescent antibody test of these two microorganisms in the lower genital tract in
is also available to detect recent or past infection but is more sexually active women has been reported to be 40% to 95%
useful as a research tool than for the clinical diagnosis of for U. urealyticum and 15% to 70% for M. hominis. Their high
chlamydial infection. prevalence rates among otherwise healthy women make it
difficult to determine their role in adverse pregnancy out-
Management Options comes. In general, M. hominis has been associated in some,
but not all, studies with septic abortion, postpartum endo-
PREPREGNANCY metritis, and postpartum fever.107,108,114 U. urealyticum has
C. trachomatis is susceptible to a wide range of antibiotics been associated with histologic chorioamnionitis, low birth
including azithromycin, erythromycin, doxycycline, tetra- weight, and perinatal death.115–119
cycline, and ofloxacin. For the nonpregnant patient, Serologic evidence of infection with M. hominis has been
azithromycin 1 g orally in a single dose or doxycycline found in 50% of febrile abortions versus 17% of afebrile
100 mg orally two times a day for 7 days is the recom- abortions.113 In one study of early postpartum endometritis
mended regimen.95 Alternate regimens include erythromy- among women, genital mycoplasmas, including M. hominis,
cin base 500 mg orally four times daily for 7 days, accounted for 30% of the total endometrial isolates and 19%
erythromycin ethylsuccinate 800 mg orally four times daily of the total blood isolates, but were usually recovered in
for 7 days, ofloxacin 300 mg orally twice a day for 7 days, association with other pathogenic bacteria, suggesting a
or levofloxacin 500 mg orally once daily for 7 days. For mixed infection.114 M. hominis has also been isolated from
nonpregnant women, test of cure is not required, but fol- amniotic fluid of patients with amniotic fluid infection, but
low-up testing approximately 3 months after treatment is almost always in association with other bacteria, again
recommended.95 implying a mixed infection.28 Significantly, infected patients
from whom M. hominis is recovered almost always respond to
PRENATAL therapy with β-lactam antibiotics, which have no activity
In pregnancy, azithromycin 1 g orally in a single dose or against genital mycoplasmas.
amoxicillin 500 mg orally three times a day for 7 days is A number of studies have found an association between
recommended. Alternate regimens include erythromycin U. urealyticum and chorioamnionitis116,117,119 and with peri-
base 500 mg orally four times a day for 7 days or 250 mg natal death.117,120 In one study, U. urealyticum was isolated as
orally four times daily for 14 days, or erythromycin ethyl- the sole isolate from fetal lungs in 24 (8%) of 290 perina-
succinate 800 mg orally four times a day for 7 days or tal deaths.120 Twenty-two of these deaths occurred in utero
400 mg four times daily for 14 days (see Table 32–6).95 and all but 1 were associated with pneumonia and chorio-
Erythromycin estolate should probably not be used because amnionitis, implying an ascending intrauterine infection.
it may be associated with hepatotoxicity when given during Some studies have also found decreased birth weight
pregnancy. Because erythromycin therapy is frequently among offspring of women colonized with U. urealyticum,115
associated with gastrointestinal intolerance in pregnancy, but this association has not been confirmed by others.106
regimens avoiding erythromycin might be preferable. Intervention treatment trials have also been inconclusive.
Therapy with either amoxicillin, 500 mg orally three times McCormack and associates121 demonstrated an increase in
a day for 7 days, or clindamycin, 450 mg orally four times birth weight among the offspring of women colonized
a day for 14 days, results in cure rates (98% and 93%, with U. urealyticum treated with erythromycin in the third
respectively) comparable with cure rates with erythromy- trimester compared with colonized women treated with
cin base therapy and are better tolerated by the placebo. Because the presence of potential genital patho-
patient.111,112 Sexual contacts should be examined and gens was not ascertained, their potentially confounding
treated. influence upon birth weight cannot be excluded. In
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536 S ECTION F OUR • Infection
contrast, Eschenbach and coworkers122 found no beneficial be taken from the base of the ulcer and placed on selective
effect of erythromycin taken for up to 14 weeks by a large media. Cultures are both sensitive and specific in the diag-
cohort of women colonized for U. ureaplasma on birth nosis of H. ducreyi infection, but might not be readily avail-
weight, gestational age at delivery, frequency of PROM, able from commercial sources. An enzyme-linked
or neonatal outcome. In this study, women also colonized immunosorbent assay has been developed that is both sensi-
with either C. trachomatis or GBS were excluded from analy- tive and specific and may represent a good alternative when
sis, eliminating any potential confounding bias from culture is not available.
co-infection.
Management Options
Management Options H. ducreyi is susceptible to a variety of antibiotics, although
Taken collectively, the data linking either M. hominis or U. resistance to sulfonamides and tetracycline has emerged that
urealyticum to adverse pregnancy outcome are inconclusive. precludes their use. Quinolones, which are very active
At present, antenatal vaginal cultures for either of these against H. ducreyi, are contraindicated during pregnancy.
mycoplasmas cannot be recommended. Current evidence Current recommended regimens that may be given in preg-
does not support the treatment of colonized patients for nancy include (1) azithromycin 1 g orally in a single dose;
the prevention of adverse pregnancy outcomes. If treat- (2) erythromycin base 500 mg three times daily for 7 days;
ment is deemed necessary, tetracycline is effective against and (3) ceftriaxone 250 mg intramuscularly as a single dose.
both M. hominis and U. urealyticum but should not be used in Azithromycin and ceftriaxone offer the advantage of single-
pregnancy. U. urealyticum is also sensitive to erythromycin dose therapy. It is recommended that patients are tested for
but is resistant to clindamycin; M. hominis is resistant to HIV at the time of diagnosis, and retested for syphilis and
erythromycin but sensitive to clindamycin. Because the HIV 3 months after diagnosis, and that sexual partners of
mycoplasmas lack a cell wall, they are resistant to β-lactam patients are examined and treated.95
antibiotics.
Lymphogranuloma Venereum
Chancroid Lymphogranuloma venereum (LGV) is a sexually trans
Chancroid is an acute ulcerative disease, usually of the geni- mitted disease caused by C. trachomatis serovars L1, L2, and
tals, caused by infection with Haemophilus ducreyi, a faculta- L3. Transmission occurs through vaginal, anal, or oral
tive gram-negative bacillus. Although rare in North America sexual contact with mucosal damage. It is characterized by
and Europe, it remains an important public health concern inguinal lymphangitis, anogenital lesions, and fibrosis with
in developing countries and can potentially be introduced gross distortion of the perineal tissues. LGV is endemic in
into other geographic areas as a result of travel. Chancroid certain parts of the world, including Africa, India, South-
may occur more frequently in individuals infected with east Asia, and parts of South America.124 It occurs sporadi-
HIV, genital herpes, or syphilis. Chancroid is spread only cally in other geographic locations and was very rarely
through sexual contact with individuals with ulcers and is seen in industrialized countries in North America, Europe,
much more prevalent in men than in women. The incuba- or Australia until more recently. Beginning in 2003, clus-
tion period after transmission is usually between 4 and 7 ters of cases have been identified in Europe, Canada, and
days. A painful chancre then develops at the site of entry, the United States.125 LGV is predominantly a disease of
beginning as a small papule that over the course of 1 to 2 lymphatic tissue characterized by thrombolymphangitis
days, becomes eroded and ulcerated. Multiple ulcers are and spread of the inflammatory process into the adjacent
common, with the majority occurring on the external geni- tissues. Three stages of infection are recognized: primary,
tals and only rarely on the cervix or vagina. The classic ulcer secondary, and tertiary. The primary lesion is character-
of chancroid is shallow with an irregular border surrounded ized by a small shallow genital papule or ulcer that appears
by erythema. The base of the ulcer is frequently covered at the site of infection after an incubation period of 3 to
with a necrotic exudate. Painful inguinal adenopathy devel- 12 days, heals rapidly, and is often associated with few
ops in about 50% of cases and may lead to suppuration and symptoms. The secondary stage occurs 10 to 30 days later
spontaneous rupture if untreated. These buboes appear 7 to and is characterized by systemic symptoms and painful
10 days after the initial ulcer and are unilateral in two thirds inguinal lymphadenitis or buboes, loculated abscesses, and
of cases. anorectal symptoms such as pain and bleeding. The ter-
tiary stage is characterized by a chronic inflammatory
Maternal and Fetal Risks response with progressive tissue destruction, ulceration,
H. ducreyi has not been shown to cause systemic infection fistula formation, and lymphatic obstruction. Antibiotic
or spread to distant sites and poses no special risk to treatment during the secondary stage will prevent these
pregnancy. tertiary complications.
Diagnosis
The diagnosis of chancroid is based upon clinical character- Maternal and Fetal Risks
istics (the presence of a painful ulcer and tender adenopathy) The course of the disease is not dramatically altered by
and Gram stain and culture of the ulcer or aspirated bubo. pregnancy, and transmission to the fetus does not occur.
The Gram stain may reveal gram-negative rods that form However, infection may be acquired during birth and
chains but has a sensitivity of only 50%.123 Cultures should passage through the infected birth canal.
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C HAPTER 31 • Other Infectious Conditions 537
Gonorrhea
Prepregnancy
Identify and treat prior to pregnancy. III/B 92,95
Contact tracing and treatment. III/B 92,95
Confirm response with follow-up swabs. III/B 92,95
Prenatal
Give antibiotics (see Table 31–6). III/B 92
Contact tracing and treatment. III/B 92
Exclude chlamydia infection. III/B 96
Postnatal
Screen newborn for infection, although most units treat anyway. —/GPP —
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538 S ECTION F OUR • Infection
Chlamydia
Prepregnancy
Identify and treat with doxycycline or ofloxacin. Ia/A 95,109,111,112
Contact tracing and treatment. Ia/A 95,109,111,112
Prenatal Treatment
If diagnosed, give antibiotics (see Table 31–6). Ia/A 95,109,111,112
Contact tracing and treatment. Ia/A 95,109,111,112
Mycoplasma
Prenatal
If treatment necessary, use erythromycin. Ia/A 122
Chancroid
Prenatal
Treatment of patient and partner with either azithromycin, IV/C 95,124
erythromycin, or a cephalosporin.
Lymphogranuloma Venereum
Prenatal
Erythromycin if diagnosed in pregnancy. Azithromycin is a IV/C 95,124
possible alternative.
Fistulas or strictures may need repair after pregnancy. IV/C 95,124
Granuloma Inguinale
Prenatal
Erythromycin if diagnosed in pregnancy. Azithromycin is a IV/C 95,126,127
possible alternative. Treatment should continue for a minimum
of 3 wk.
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C HAPTER 31 • Other Infectious Conditions 539
albicans to vaginal epithelial cells. Finally, cell-mediated studies demonstrating an association between bacterial
immunity is impaired during pregnancy, predisposing to vaginosis and preterm birth. Despite this evidence, the
candidal infections. strategy of screening for and treatment of bacterial vagino-
The three most commonly occurring causes of infectious sis in large-scale studies of women at low risk of adverse
vaginitis in pregnancy are bacterial vaginosis, candidiasis, obstetric outcomes has not resulted in a reduction in the
and trichomoniasis. Although frequently asymptomatic, incidence of prematurity. Thus, the U.S. Preventive Ser-
these infections have been implicated in a variety of adverse vices Task Force published a statement in 2001 concluding
pregnancy outcomes. that the available evidence was insufficient to recommend
for or against routinely screening women at high risk
preterm birth for bacterial vaginosis and recommending
Bacterial Vaginosis against screening average risk asymptomatic pregnant
Bacterial vaginosis is the most common lower genital tract women.139
disorder among women of reproductive age (pregnant and Little is known about the mechanisms by which bacterial
nonpregnant) and the most prevalent cause of vaginal dis- vaginosis may cause prematurity. The increased intravaginal
charge and malodor.132,133 It is a polymicrobial syndrome concentrations of bacteria may simply overwhelm the local
resulting in a decreased concentration of lactobacilli and an host defenses, allowing for ascending infection. Alterna-
increase in pathogenic bacteria (mainly anaerobic). Specifi- tively, these bacteria could also produce protease or phos-
cally, there is an increased prevalence of G. vaginalis, selected pholipases, which weaken the membranes or stimulate
anaerobes (Bacteroides, Peptostreptococcus, and species), and M. prostaglandin production.140 Although the magnitude of the
hominis and a decreased prevalence of hydrogen peroxidase– increased risk for prematurity noted in these studies is
producing Lactobacillus.131,134 In addition, there is a 100-fold modest (approximately a twofold increased risk compared
increase in the intravaginal concentration of G. vaginalis and with patients without bacterial vaginosis), the total impact
a 1000-fold increase in the concentration of anaerobes.134 upon prematurity may be much greater given the high prev-
Thus, the diagnosis of bacterial vaginosis does not depend alence of 20% for bacterial vaginosis in pregnancy. It has
upon the recovery or identification of any single microor- been estimated that as many as 6% of preterm deliveries of
ganism from the vagina, but rather requires the recognition infants with low birth weight may be attributable to bacterial
of an altered vaginal microbial milieu. vaginosis.135
Maternal and Fetal Risks Diagnosis
The presence of bacterial vaginosis has consistently been The most common symptom among women with bacterial
shown to be a risk factor for adverse pregnancy outcomes vaginosis is a thin, watery, nonpruritic discharge with a fishy
such as preterm labor and delivery, preterm PROM, spon- odor. However, one half of women with bacterial vaginosis
taneous abortion, chorioamnionitis, and postpartum infec- are asymptomatic.
tions such as endometritis and cesarean section wound Criteria for the clinical diagnosis of bacterial vaginosis are
infections.118,135–139 Table 31–7 presents a summary of well established, with the diagnosis confirmed if three of the
four following signs are present141: (1) an adherent and
homogeneous vaginal discharge; (2) a vaginal pH above 4.5;
(3) detection of clue cells on saline wet mount; and (4) the
T A B L E 3 1 – 7 release of an amine (fishy) odor after the addition of 10%
Association between Bacterial Vaginosis and potassium hydroxide (positive whiff test). The diagnosis of
Preterm Labor or Preterm Birth bacterial vaginosis can also be made by direct Gram stain of
the vaginal discharge. The Gram stain is the most widely
RISK RATIO OR 95% CONFIDENCE used and evaluated microbiologic diagnostic method for this
STUDY ODDS RATIO INTERVAL
condition. Most laboratories use an objective diagnostic
Case-Control scheme that quantifies the number of Lactobacillus morphot-
Eschenbach, 1984131 3.1 1.6–6.0 ypes and pathogenic bacteria, resulting in a score that is used
Gravett, 1986166 3.8 1.2–11.6
to determine whether the infection is present. The most
commonly used system is the Nugent score.142 The criterion
Martius, 1988167 2.3 1.1–5.0
for bacterial vaginosis is a score of seven or higher. A score
Prospective Cohort of four to six is considered intermediate, and a score of zero
Minkoff, 1984136 2.3 0.96–5.5 to three is considered normal.
Gravett, 1986103 2.0 1.1–3.7
McGregor, 1990168 2.6 1.1–6.5 Management Options
McDonald, 1991169 1.8 1.01–3.2 The treatment of choice for symptomatic bacterial vaginosis
Kurki, 1992170 6.9 2.5–18.8 in pregnancy is metronidazole given orally in a dose of
Riduan, 1993171 2.0 1.0–3.9 500 mg twice daily for 7 days or 250 mg three times daily
McGregor, 1994146 3.3 1.2–9.1 for 7 days.95 This results in cure rates of 90%. A single 2-g
Hay, 1994172 5.2 2.0–13.5
oral dose of metronidazole is also effective. Oral clindamy-
cin 300 mg twice a day for 7 days may be used as an alterna-
McGregor, 1995173 1.9 1.2–3.0
tive. Nitroimidazoles cross the placenta and are mutagenic
Meis, 1995174 1.8 1.15–2.95
in bacteria and carcinogenic in some animals. However,
Hillier, 1995135 1.4 1.1–1.8 there is no evidence that metronidazole is teratogenic or
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540 S ECTION F OUR • Infection
mutagenic in human studies, and it is considered safe for be recovered from the vagina in 25% to 40% of asymptom-
use in pregnancy.143,144 Cure rates utilizing topical therapy atic women. Candida also accounts for approximately 25% of
are comparable with those of systemic therapy.145 However, all symptomatic vaginitis among nonpregnant patients and
vaginal preparations such as metronidazole vaginal gel up to 45% of vaginitis in pregnancy. In pregnancy, altera-
0.75%, given intravaginally once daily for 5 days, or clinda- tions in the vaginal microflora, glycogen availability, and a
mycin cream 2.0%, given intravaginally once daily for 7 depression in maternal cellular immunity may all contribute
days have not been shown to be effective for preterm to increase the risk of Candida overgrowth leading to vagini-
birth prevention, and therefore, oral agents are preferred. tis. Although rare, C. albicans has been reported as a cause of
Further studies are necessary to address this important amniotic fluid infection and congenital cutaneous candidia-
consideration. sis of the newborn.157
The results of trials examining whether the treatment of
bacterial vaginosis in pregnancy can affect the frequency of
adverse pregnancy outcomes, especially preterm birth, have Diagnosis
been inconsistent. In trials enrolling women from the general Women with vaginal candidiasis experience vulvar and
population who are not at increased risk for preterm birth, vaginal pruritus, external dysuria, and a nonmalodorous floc-
there does not appear to be any benefit to screening for and culent discharge. Examination usually reveals an erythema-
treating bacterial vaginosis. These results have been repli- tous vulvar rash and a characteristic white “cottage cheese”
cated in many studies from different countries, enrolling discharge that adheres to the vaginal walls. The vaginal pH
women at a range of gestational ages, and using both oral is usually normal (<4.5) and no odor is present. Microscopic
and vaginal medications (metronidazole and clindamy- examination of material suspended in 10% potassium
cin).146–151 However, in women at increased risk for prema- hydroxide reveals typical mycelial forms and pseudohyphae
ture birth (often defined as having a history of a previous in 80% of patients with symptomatic infection. Because
preterm delivery), there have been more promising results. Candida species may exist in the vaginal flora in low concen-
Several studies have shown that women randomized to treat- trations among normal asymptomatic patients, cultures are
ment with oral metronidazole had lower rates of adverse usually not indicated. Cultures should be limited to women
outcomes, including preterm labor and delivery, than women in whom candidiasis is suspected but cannot be confirmed
randomized to placebo.150,152,153 In a Cochrane Collaboration by microscopic examination.
review154 of 15 treatment trials involving 5888 women, there
was a statistically significant decrease in the rate of preterm
prelabor rupture of membranes and low birth weight in Management Options
treated women with a history of previous preterm birth, but Treatment by local application of antifungals results in relief
no effect on preterm delivery rates. However, in the same of symptoms and eradication of yeast in 70% to 90% of
review, there was a statistically significant decreased risk of patients. The mainstay of treatment has been with imidaz-
preterm birth in five trials of 2387 women treated before 20 oles. These broad-spectrum antifungals include miconazole,
weeks’ gestation.154 clotrimazole, teraconazole, and butaconazole. These agents
In published studies, vaginal therapy has not been shown inhibit fungal ergosterol synthesis, resulting in disruption of
to be effective in preventing preterm birth in women with the cell membrane. They are available as a one-time intra-
bacterial vaginosis.146–149 The one exception to this is a trial vaginal suppository or as either 3-day or 7-day courses of
by Lamont and colleagues155 that demonstrated a statistically intravaginal suppositories or creams given once daily at
significant reduction in preterm birth (4% vs. 10%) in bedtime. These imidazoles are not absorbed systemically
women randomized to clindamycin vaginal cream at 13 to and are safe to use in pregnancy. In pregnant women, the
20 weeks’ gestation compared with placebo. A meta-analysis 7-day course is recommended.95 Boric acid powder, in
exploring the issue of oral or vaginal treatment in women at 600 mg vaginal suppositories, placed intravaginally daily for
low risk versus those at high risk for preterm birth found no 14 days is also 90% effective in eradicating symptomatic
significant reduction in preterm delivery by treatment of all vaginal candidiasis and has the advantage of being very
women, women with a previous preterm birth, or women at inexpensive.158 Although borate is poorly absorbed systemi-
low risk for preterm birth.156 However, in the subgroup of cally in nonpregnant women, its absorption during preg-
women who had a previous preterm delivery and who had nancy is uncertain, and therefore, alternative therapies with
received oral treatment for at least 7 days, there was a highly topical imidazoles are preferable. Two other antifungal
significant decrease in preterm delivery (odds ratio [OR] agents that are systemically absorbed after oral or intrave-
0.42; 95% confidence interval [CI] 0.27–0.67). There was nous administration are ketoconazole, an imidazole, and
no benefit seen in the group of women receiving vaginal fluconazole, a triazole. These both have superb activity
treatment. against Candida species and are useful in the treatment of
systemic fungal infections or vaginal candidiasis in nonpreg-
Candida Vaginitis nant women.
Maternal and Fetal Risks
Candida vaginitis may be caused by many species of Candida, Trichomoniasis
but the predominant species is C. albicans, which is respon- Trichomoniasis is caused by T. vaginalis, a sexually transmit-
sible for 80% to 90% of infections. The remainder of cases ted anaerobic protozoan. T. vaginalis may be recovered from
are caused by Candida (Torulopsis) glabrata and other Candida 40% of women screened in sexually transmitted disease
species. These organisms are saprophytic fungi, which may clinics and from the prostatic fluid of 70% of the male
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C HAPTER 31 • Other Infectious Conditions 541
contacts of the women with symptomatic trichomonia- However, cultures have limited practicality in the clinical
sis.159,160 The prevalence of trichomoniasis in pregnancy setting because 3 to 7 days are needed for growth before the
ranges from 6% to 22%. Risk factors associated with T. vagi- diagnosis can be confirmed. Trichomonads can also be seen
nalis colonization include black race, cigarette smoking, on a Pap smear with a similar sensitivity to the wet mount,
greater number of sexual partners, and a history of gonor- but with a higher rate of false-positive results. Other sensi-
rhea.161 It is estimated that approximately 50% of women tive and specific rapidly performed diagnostic tests have
harboring T. vaginalis are asymptomatic.159 recently been developed, including direct immunofluores-
cence assay, enzyme-linked immunoassay, and LPA. These
are not, however, in widespread use currently. All women
Maternal and Fetal Risks with trichomoniasis, whether symptomatic or not, should
Pregnant women with T. vaginalis infection may be asymp- have a culture taken for N. gonorrhoeae because of the fre-
tomatic or may have clinical vaginitis. T. vaginalis may also quency of coinfection.
cause other infections of the lower genitourinary tract
including bartholinitis, urethritis, periurethral gland infec-
tion, and cystitis. Although the risk of infection to the Management Options
neonate is low (<1%), vaginitis and cystitis may occur as Because T. vaginalis resides not only in the vagina but also in
manifestations of neonatal disease. T. vaginalis has also been the urethra and bladder, systemic therapy is necessary for
rarely suspected as a cause of neonatal pneumonitis. Although treatment. The only effective therapy for trichomoniasis are
the relationship between vaginal trichomoniasis and adverse the nitroimidazole antibiotics, including metronidazole,
pregnancy outcome has not been well studied, two prospec- ornidazole, and tinidazole. For pregnant women who are
tive studies have found a decrease in mean gestational age symptomatic, treatment is recommended. However, it is
at delivery and an increase in PROM among women infected important to note that, although trichomoniasis has been
with T. vaginalis.99,136 Further studies are necessary to confirm associated with adverse pregnancy outcomes, treatment has
these relationships. not been shown to reduce the incidence of these adverse
events,135 and some studies have even documented an
Diagnosis increased risk with treatment. Therefore, treatment is not
Women with symptomatic trichomoniasis characteristically indicated in asymptomatic T. vaginalis infection in preg-
complain of a profuse and malodorous vaginal discharge. nancy. In a randomized, controlled trial of pregnant women
Vulvar pruritus, dysuria, dyspareunia, and lower abdominal with asymptomatic trichomoniasis, the preterm birth rate
tenderness may also be present. On examination, a gray or was 19% in those given two 2-g doses of oral metronidazole
yellow-green frothy discharge is frequently present. The pH and 10% in the placebo group (RR 1.8; 95% CI 1.2–2.7; P
of the discharge is usually higher than 4.5 and may have an = .004).163 In another randomized trial, children of women
amine odor after addition of 10% potassium hydroxide. treated with several antibiotics including metronidazole had
Small submucosal punctate hemorrhages of the cervix, the an increased risk of low birth rate, preterm delivery, and
so-called strawberry cervix, are sometimes present. Micro- 2-year mortality.164 Finally, a meta-analysis of 14 studies
scopically, motile trichomonads may easily be identified on revealed that metronidazole treatment increased the inci-
a saline wet mount by their characteristic pear shape, fla- dence of preterm birth.165
gella, and rapid, jerking motility. Polymorphonuclear leuko- For pregnant women in whom treatment is chosen, the
cytes are also present on saline wet mount microscopy and preferred regimen is a single 2-g dose of oral metronidazole.
may be so abundant that they obscure the trichomonads. Simultaneous treatment of sexual partners is required to
The sensitivity of the saline wet mount, when compared prevent reinfection. As previously mentioned, there is no
with culture, is 60%, but its specificity is near 100%.162 evidence that metronidazole is teratogenic or mutagenic in
Trichomonas cultures are easily performed utilizing Diamond’s human studies, and it is considered safe for use in
medium and are highly sensitive (92%–95%) and specific. pregnancy.143,144
Bacterial Vaginosis
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542 S ECTION F OUR • Infection
Candidiasis
Trichomonas
Nugent RP, Krohn MA, Hillier SL: Reliability of diagnosing bacterial vagi-
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For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.