Bacterial Infections and Pregnancy

Bacterial infections can affect pregnant individuals from implantation of the fertilized ovum through the time of delivery and peripartum period. They also may affect the fetus and newborn. Many pregnant patients with these infections are asymptomatic, necessitating both a high degree of clinical awareness and adequate screening.

Group B Streptococcus

Group B Streptococcus (GBS; Streptococcus agalactiae) is the most common cause of life-threatening infections in newborns and also can affect the mother. Features of GBS infection are as follows:

• GBS can be found as part of normal vaginal, rectal, and oral flora

• Intrapartum transmission occurs via ascending spread or at the time of delivery

• In pregnant people, GBS causes cystitis, amnionitis, endometritis, and stillbirth; occasionally, GBS bacteremia leads to endocarditis or meningitis

• In postpartum patients, GBS can cause urinary tract infections (UTIs) and pelvic abscesses

• In newborns, early-onset GBS infection occurs before age 7 days (mean age at presentation is age 12 hours) and primarily manifests as nonfocal sepsis, pneumonia, or meningitis

• Late-onset disease in neonates occurs at age 7-89 days (mean age, 36 days), and nonfocal bacteremia and meningitis are the most common presentations

• Babies who survive the initial insult face possible hearing or vision loss, learning disabilities, and other neurologic sequelae

CDC recommendations are as follows:

• At 35-37 weeks’ gestation, all pregnant patients should undergo screening with a vaginal and rectal swab for culture ^[1]

• The most specific site for culture is at the introitus, just inside the hymeneal ring and rectally beyond the sphincter; cervical, perianal, perirectal, or perineal specimens are not acceptable, and speculum should not be used for culture collection ^[2]

• If the culture result is positive, the patient should be treated during labor

If culture results are unknown at the time of delivery, a risk-based approach can be used, in which patients are deemed at high risk and receive treatment if they meet any of the following criteria:

• Previously delivered infant with invasive GBS infection

• GBS bacteriuria during current pregnancy

• Delivery before 37 weeks' gestation

• Duration of ruptured membranes longer than 18 hours

• Intrapartum temperature higher than 100.4°F (38°C)

High-risk patients with negative screening culture results within 5 weeks of delivery do not require treatment.

Treatment is as follows:

• During labor and until delivery, IV penicillin G or ampicillin.

• In patients with known penicillin allergy, sensitivities of the GBS isolate should be sent, although IV cefazolin is the best choice in penicillin-allergic patients at low risk for anaphylaxis; in those at high risk for anaphylaxis, IV clindamycin or erythromycin is an acceptable alternative

• If susceptibility to clindamycin or erythromycin has not been established, IV vancomycin can be used

• The neonate must be carefully observed for signs and symptoms of disease

Urinary tract infections

Asymptomatic bacteriuria develops in 10-15% of pregnant women and can lead to complications such as pyelonephritis and premature labor, so all pregnant individuals should undergo screening with urine culture at least once during early pregnancy and should be treated if the results are positive. ^{[3, 4]} Significant bacteriuria is defined as >100,000 colony-forming units (CFU) of a single organism in a clean-catch specimen.

Treatment is as follows:

• Initial antibiotic therapy may be empiric, followed by tailoring to the pathogen grown in the urine

• Sulfonamides, amoxicillin, amoxicillin-clavulanate, cephalexin, and nitrofurantoin are acceptable

• Sulfonamides in the last few weeks of gestation may lead to kernicterus and hyperbilirubinemia in the newborn

• Trimethoprim is relatively contraindicated during the first trimester due to theoretical teratogenicity

• Nitrofurantoin may cause hemolysis in patients or fetuses with G6PD deficiency

• A 7-day regimen treats bacteriuria and acute cystitis; single-dose therapy is less effective

• Recurrent UTIs may warrant postcoital prophylaxis with single-dose cephalexin or nitrofurantoin macrocrystal

• Apart from the need to avoid certain antibiotics, treatment of pyelonephritis in pregnant patients mirrors that in nonpregnant patients

• Mild cases may be treated in an outpatient setting, but more severe cases may necessitate hospitalization and IV antibiotics plus IV hydration for nausea, vomiting, and dehydration

• Pregnant patients who have had acute pyelonephritis should be monitored frequently with repeat urine cultures; if close follow-up care is not practical, continuous suppressive therapy can be considered

Listeriosis

Features of infection with Listeria monocytogenes are as follows:

• Approximately one third of all reported cases of listeriosis occur during pregnancy, typically during the third trimester

• Infection mainly follows ingestion of contaminated food, but rare cases after direct contact with infected animals and nosocomial transmission have been reported

• The most common clinical presentation in pregnant patients with listeriosis is bacteremia, often asymptomatic; CNS Listeria infections are rare, unlike in other populations

• Symptomatic pregnant patients often have a febrile illness similar to influenza with fever, muscle aches, and, occasionally, nausea or diarrhea during the bacteremic phase of the disease

• Although maternal symptoms may be mild, listeriosis can lead to amnionitis and result in spontaneous septic abortion, premature labor with delivery of an infected baby, or even stillbirth ^[5]

• Fetal infection may manifest as septicemia, meningoencephalitis, or disseminated granulomatous lesions with microabscesses

• Confirming a diagnosis of listeriosis requires a culture showing L monocytogenes in blood or CSF

• Serologic testing is unreliable for diagnosis, and stool cultures are not sensitive or specific

• Treatment is with IV ampicillin or penicillin; patients with beta-lactam allergy should be desensitized

• Trimethoprim/sulfamethoxazole is the usual alternative for patients allergic to penicillin but can be problematic during the first or third trimesters

Syphilis

Features of syphilis are as follows:

• Untreated primary or secondary syphilis in pregnancy leads to a fetal infection rate of almost 100%

• The disease can cause stillbirth; late abortion; or neonatal disease, death, or latent infection ^[6]

• In primary syphilis, a hard, painless red ulcer typically forms on the vulva, cervix, or vagina

• Secondary syphilis predominantly manifests as a nonpruritic rash that may involve the palms and soles; fever, lymphadenopathy, and joint pain are less common manifestations of secondary syphilis

• The latent stage causes no symptoms and is still transmissible to the fetus

• Tertiary syphilis can result in cardiovascular or gummatous disease

• Neurosyphilis can occur at any stage, resulting in CNS or ophthalmic presentations

• All pregnant patients should undergo syphilis screening in early pregnancy. ^[7]

• Serologic tests should be performed at the initial prenatal visit in all pregnant patients; those considered high risk should have repeat testing at 28 weeks' gestation and at delivery ^[8]

• Nontreponemal antibody test results (eg, RPR, VDRL) often are false-positive in pregnant patients; therefore, positive findings should be confirmed with specific antitreponemal antibody tests such as the microhemagglutination assay– T pallidum (MHA-TP) and the fluorescent treponemal antibody absorption test (FTA-ABS)

• Once syphilis is diagnosed, consider other sexually transmitted diseases, especially HIV

• Treatment is with a single dose of 2.4 million units of IM benzathine penicillin for primary, secondary, and early latent syphilis, but some experts recommend a second dose of benzathine penicillin G 1 week after the initial dose, especially in the third trimester or in patients with secondary syphilis

• In late latent syphilis, treatment consists of 3 doses of benzathine penicillin, each 1 week apart; if results of subsequent quantitative VDRL or an equivalent test show a 4-fold increase, re-treat the patient and perform a lumbar puncture to rule out neurosyphilis

• Pregnant individuals who are allergic to penicillin must be desensitized and then treated with penicillin

• Jarisch-Herxheimer reactions in pregnancy may involve uterine contractions, preterm labor, and premature delivery

Chlamydia

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States and continues to be a major cause of complications in pregnancy and disease transmission in newborns. Features of Chlamydia infection are as follows:

• Approximately 75% of women with C trachomatis infection are asymptomatic

• C trachomatis can cause endometritis, cervicitis, acute pelvic inflammatory disease (PID), and acute urethral syndrome in all women and chorioamnionitis, postpartum endometritis, and gestational bleeding in pregnant patients

• The usual mode of transmission to the fetus is vertical during the second stage of labor

• In neonates, C trachomatis infection commonly causes conjunctivitis (ophthalmia neonatorum) and pneumonia

• All pregnant patients should undergo Chlamydia screening early in pregnancy; those younger than 25 years and high-risk patients should be screened again in the third trimester ^[9]

• Patients diagnosed with chlamydial infection in the first trimester should be retested 3-6 months later

According to the CDC, the following are the accepted screening methods ^{[10, 11]} :

• A nucleic acid amplification test (NAAT) performed on urine or an endocervical swab specimen

• An unamplified nucleic acid hybridization test, an enzyme immunoassay, or direct fluorescent antibody test performed on an endocervical swab specimen

• Culture performed on an endocervical swab specimen

Treatment is as follows:

• Azithromycin (first-line recommended therapy) ^[12]

• Amoxicillin (alternative agent)

• Erythromycin (second-line agent because of compliance-limiting GI adverse effects)

• Tetracyclines and fluoroquinolones are contraindicated in pregnant individuals

• Retest treated pregnant patients 3 weeks after therapy to ensure therapeutic cure

Gonorrhea

Features of Neisseria gonorrhoeae infection are as follows:

• Gonococcal infections are second only to chlamydial infections in the number of cases of bacterial STDs

• Gonococcal infections cause no symptoms in approximately 50% of patients

• Pregnancy is a predisposing factor to the development of disseminated gonococcal infection, which classically presents as an arthritis-dermatitis syndrome

• Newborns exposed to gonorrhea during vaginal delivery can develop an acute conjunctivitis (ophthalmia neonatorum), sepsis, arthritis, and/or meningitis

• The American College of Obstetricians and Gynecologists recommends screening (via endocervical culture) in high-risk pregnant patients on their first antenatal visit

• The CDC recommends screening all pregnant individuals "at risk for gonorrhea," with rescreening in the third trimester for those at continued risk

• The recommended screening method remains endocervical culture; alternatives include the NAAT and the nucleic acid hybridization test

• Culture, nucleic acid hybridization, and NAAT tests can all be used for diagnosis

• The treatment of choice for uncomplicated cervicitis is single-dose IM ceftriaxone and oral azithromycin

Bacterial vaginosis

Bacterial vaginosis is a clinical syndrome caused by excessive growth of bacteria that normally may be present in the vagina. Features of bacterial vaginosis are as follows:

• The etiology is polymicrobial in nature; with a pH of more than 4.5, Gardnerella vaginalis and anaerobes become the prominent associated organisms

• Patients with bacterial vaginosis may be asymptomatic or may report an abnormal vaginal discharge with an unpleasant, fishlike odor, especially after sexual intercourse

• The discharge is generally white or gray, and patients may experience burning during urination or itching around the vagina

• Infection can lead to premature labor unresponsive to tocolytic therapy

• Infection can be transmitted via the placenta to the fetus and can cause intrauterine fetal death

A diagnosis of bacterial vaginosis can be confirmed via clinical or Gram stain criteria. When using the clinical criteria, 3 of the following 4 conditions should be present:

• A homogeneous, white, noninflammatory discharge that smoothly coats the vaginal wall

• Clue cells (ie, vaginal epithelial cells that have a stippled appearance due to aggregates of coccobacilli)

• Vaginal fluid pH of more than 4.5

• A positive whiff test result (ie, a fishy odor to the vaginal discharge before or after the addition of 10% potassium hydroxide solution)

• Oral metronidazole or clindamycin is recommended; clindamycin cream should be avoided during the second half of pregnancy

This article focuses on common bacterial infections in pregnancy and describes the manifestations of these infections and the therapies used to treat them.

Bacterial infections can affect pregnant women from implantation of the fertilized ovum through the time of delivery and peripartum period. They may also affect the fetus and newborn. Many women with these infections are asymptomatic, necessitating both a high degree of clinical awareness and adequate screening.

Group B Streptococcus(GBS) is the most common cause of life-threatening infections in newborns; thus, GBS is the primary focus of any discussion about infections and pregnancy. Infections caused by GBS affect both mother and child. Since the emergence of this pathogen in the 1970s, the increased use of intrapartum prophylaxis has decreased the infection rate by 70%. The incidence of invasive early-onset GBS infection in neonates decreased from 1.7 cases in 1000 live births in 1990 to 0.3 in 1000 live births in 2005. ^[13]

Etiology

Streptococcus agalactiae, or GBS, is a facultative, beta-hemolytic, fastidious, gram-positive coccus. GBS can be found as part of normal vaginal, rectal, and oral flora. The virulence of the organism depends largely on the polysaccharide capsule.

Transmission

Twenty to 25% of pregnant patients are asymptomatic carriers of vaginal or rectal GBS. Intrapartum transmission occurs via ascending spread or at the time of delivery. The rate of vertical transmission in neonates born to individuals infected with GBS is about 50%. ^[14]

Clinical spectrum

Because only 0.5-1% of mothers who carry GBS develop signs and symptoms of disease, clinical diagnosis of GBS infection can be problematic.

In pregnant people, GBS is a cause of cystitis, amnionitis, endometritis, and stillbirth. Occasionally, GBS may cause bacteremia leading to endocarditis, and meningitis in pregnant patients, while, in postpartum patients, GBS has been identified as a cause of urinary tract infections (UTIs) and pelvic abscesses.

In newborns, GBS infection can manifest as 2 different diseases, depending on the interval between delivery and symptom onset. Early-onset disease is defined as that which occurs in neonates younger than 7 days (mean age at presentation is age 12 hours) and primarily manifests as nonfocal sepsis, pneumonia, or meningitis. Nonfocal bacteremia and meningitis are the most common presentations of late-onset disease, which occurs at age 7-89 days (mean age 36 days). Babies who survive the initial insult face possible hearing or vision loss, learning disabilities, and other neurologic sequelae.

Screening recommendation from the US Centers for Disease Control and Prevention

The US Centers for Disease Control and Prevention (CDC) recommends that all pregnant patients at 35-37 weeks’ gestation undergo screening with a vaginal and rectal swab for culture. ^[15] If the culture result is positive, they should be treated during labor. Patients who have GBS bacteriuria during the current pregnancy or who have delivered a previous infant with invasive GBS disease do not require culture and should receive intrapartum antibiotics.

If culture results are unknown at the time of delivery, a risk-based approach can be used to determine whether the mother should receive antibiotics. In this approach, high-risk patients are treated after identification using the following criteria:

• Previously delivered infant with invasive GBS infection

• GBS bacteriuria during current pregnancy

• Delivery before 37 weeks' gestation

• Duration of ruptured membranes longer than 18 hours

• Intrapartum temperature of more than 100.4°F (38°C)

However, patients with negative screening culture results within 5 weeks of delivery do not require treatment, even if these obstetric risk factors (premature delivery, prolonged rupture of membranes, intrapartum fever) develop.

Treatment/Management 

During labor, 5 million units of penicillin G should be given as an intravenous loading dose, followed by 2.5 to 3  million units every 4 hours until delivery. An alternative therapy is 2 g of ampicillin as an intravenous loading dose, followed by 1 g every 4 hours until delivery.

In patients who are allergic to penicillin and at low risk for anaphylaxis, 2 g of cefazolin can be used as an intravenous loading dose, followed by 1 g every 8 hours until delivery. Patients who are allergic to penicillin and are at high risk for anaphylaxis may be given 900 mg of intravenous clindamycin every 8 hours or 500 mg of intravenous erythromycin every 6 hours until delivery. GBS isolates from patients with a history of an anaphylactic reaction to penicillin should be tested for resistance before antibiotics are selected. If susceptibility to clindamycin or erythromycin has not been established, 1 g of intravenous vancomycin every 12 hours can be used until delivery. Neonates delivered from a mother who received prophylaxis must be carefully observed for signs and symptoms of disease.

Limitations

Although the incidence of early-onset disease has significantly declined since the recommendation and widespread institution of screening and treatment for GBS, the incidence of late-onset disease has remained stable. Furthermore, there are substantial racial disparities in the incidence of neonatal GBS disease, with a higher (and rising) rates among Black infants. The reasons for this racial disparity are unclear but have been postulated to include the higher rate of GBS colonization in pregnant Black individuals, poorer access to prenatal care, and higher rates of premature birth. ^{[16, 17]} Finally, the current approach does not affect the incidence of GBS disease in pregnant people. A vaccine may prove to be a useful adjunct in GBS disease prevention, and several are in development. ^[18]

Urinary tract infections (UTIs) are a common problem in women at all stages of life; this is particularly true of pregnant women. Women are anatomically predisposed to UTIs because of their shorter urethra and the proximity of the urethra to the anus and vagina. UTIs are an especially important topic in pregnancy, as even asymptomatic bacteriuria can lead to complications such as pyelonephritis, acute respiratory distress syndrome, and premature labor.

Etiology

The most common causative organisms include the following:

• Escherichia coli

• Klebsiella species

• Enterobacter species

• Enterococcus species

• Group B Streptococcus (GBS)

• Staphylococcus saprophyticus

• Proteus mirabilis

Clinical spectrum

Symptomatic infection and asymptomatic infection both are of clinical importance in pregnant women, unlike in healthy nonpregnant women. Infection can involve the lower or upper urinary tracts and can cause asymptomatic bacteriuria, cystitis, or pyelonephritis. The prevalence of asymptomatic bacteriuria in pregnancy is about 4-7%.

Asymptomatic bacteriuria, which develops in 10-15% of pregnant women, is not more common in pregnant women than in nonpregnant women; however, it is more likely to lead to acute pyelonephritis in pregnant women. Approximately 20-40% of pregnant women with untreated bacteriuria early in gestation develop acute pyelonephritis, compared with 14% of pregnant women without bacteriuria. Most cases of acute pyelonephritis can be prevented by treating bacteriuria early during pregnancy. ^[19] Complications of bacteriuria in pregnancy include maternal anemia, low neonatal birth weight, hypertension, and prematurity.

Cystitis is not more common in pregnant women than in nonpregnant women. The symptoms of cystitis often are confused with symptoms noted in normal pregnancy and include urgency, frequency, suprapubic discomfort, and dysuria without fever or costovertebral angle tenderness. Urine culture findings are positive, and urinalysis reveals occasional hematuria or pyuria. The effects of cystitis in pregnancy, beyond the discomfort for the woman, are unknown but likely include some of the same complications as those of asymptomatic bacteriuria.

Acute pyelonephritis is more common in pregnant women than in nonpregnant women and probably is due to stasis of urine and bacteria in the urinary tract caused by relative obstruction. This is due to dilatation of the ureters secondary to progesterone in early pregnancy and to the mechanical obstruction from the gravid uterus later in pregnancy. Second only to obstetric complications, acute pyelonephritis is the most common indication for hospitalization in pregnant patients. Acute pyelonephritis can have serious consequences for both the mother and the fetus. Although symptoms may be protean, acute pyelonephritis typically is characterized by fever, costovertebral angle tenderness, urinalysis findings with white blood cells and bacteria, and significant bacteriuria. The severity of pyelonephritis may range from minimal symptomatology to frank urosepsis. Fetal outcomes include low birth weight and prematurity.

Screening and diagnosis

Because asymptomatic bacteriuria is clinically significant in pregnancy, it should be aggressively sought, diagnosed, and treated in all stages. The Infectious Diseases Society of America (IDSA) and the US Preventive Services Task Force recommend that all pregnant individuals should undergo screening with urine culture at least once during early pregnancy and should be treated if the results are positive. ^{[3, 4]} Significant bacteriuria is defined as more than 100,000 colony-forming units (CFU) of a single organism in a clean-catch specimen.

Treatment/Management 

Any overt UTI or asymptomatic bacteriuria in pregnancy must be treated to prevent complications mentioned above.

Sulfonamides, amoxicillin, amoxicillin-clavulanate, cephalexin, and nitrofurantoin all are acceptable antibiotics. However, avoidance of sulfonamides in the last few weeks of gestation is recommended to prevent kernicterus and hyperbilirubinemia in the newborn. Trimethoprim is relatively contraindicated during the first trimester because of theoretical teratogenicity involving its antifolate activity. Nitrofurantoin may cause hemolysis in patients or fetuses with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Both sulfonamides and nitrofurantoins were associated with several birth defects in 1 recent retrospective review. ^[20]

The duration of therapy required to treat asymptomatic bacteriuria has not been determined; in a recent Cochrane review, insufficient evidence was found to recommend a specific length of therapy. ^[21] A 7-day regimen eradicates bacteriuria in 70-80% of patients and is recommended to treat acute cystitis. Single-dose therapy for asymptomatic bacteriuria is less effective. Recurrent UTIs may warrant postcoital prophylaxis with a single dose of cephalexin or nitrofurantoin macrocrystals.

Cystitis generally can be treated in the same manner as is asymptomatic bacteriuria, with the caveat that single-dose regimens are even less likely to be effective. Because these patients are symptomatic, treatment can be started before the results are confirmed with urine culture. Pregnant patients treated for cystitis should be monitored with monthly urine cultures, as approximately 20% of those who have cystitis develop another UTI during the course of their pregnancy.

Apart from the need to avoid certain antibiotics, treatment of pyelonephritis in pregnant patients mirrors that in nonpregnant patients. Although mild cases may be treated in an outpatient setting, many require hospitalization and intravenous antibiotics in addition to parenteral hydration for nausea, vomiting, and dehydration.

Initial antibiotic therapy may be empiric, followed by tailoring to the pathogen grown in the urine. Most patients with cystitis show symptomatic improvement within 1-2 days of beginning therapy; pyelonephritis can take 2-3 days to improve, even with effective therapy. If no improvement is observed, consider resistant organisms, nephrolithiasis, abscess formation, and obstruction as causes of therapy failure. Women who have experienced an episode of acute pyelonephritis should be monitored frequently with repeat urine cultures. If close follow-up care is not practical, continuous suppressive therapy can be considered.

Listeriosis is an uncommon, but perhaps underdiagnosed, cause of neonatal sepsis. Approximately 2500 cases are reported annually in the United States, with an estimated 500 fatal cases each year. Between 1989 and 1993, the annual incidence of listeriosis decreased by 44%. From 1996-2003, following food-industry regulations applied to minimize the risk of listeriosis, the incidence decreased another 24%. ^[22] Looking at listeriosis epidemiology in pregnancy, of 758 reported Listeria infection cases, 128 (16.9%) were pregnancy associated. Maternal infection resulted in 4 neonatal deaths and 26 (20.3%) fetal losses. ^[23]

Etiology

Listeria monocytogenes is a gram-positive, motile bacillus with aerobic and facultative anaerobic characteristics. The organism is found in soil and water and can be carried by animals that do not appear ill, leading to contamination of food of animal origin, particularly ready-to-eat foods such as meats and dairy products. Unpasteurized raw milks or foods are also sources of Listeria organisms.

Transmission

Pregnant women are 20 times more likely than nonpregnant women to develop listerial bacteremia. Approximately one third of all reported cases of listeriosis occur during pregnancy, typically during the third trimester when cell-mediated immunity is significantly impaired. Infection mainly has occurred after ingestion of contaminated food, although rare cases of local disease following direct contact with infected animals and nosocomial transmission have been reported.

The organism is found in soil and water. Vegetables become contaminated from the use of manure fertilizer, whereas animals may be asymptomatic carriers transmitting disease to individuals who eat their infected meat.

Outbreaks of listeriosis still are reported. Contaminated ricotta cheese caused a multistate outbreak in 2012 and led to 22 cases with 4 deaths. Nine of the illnesses were related to pregnancy and 3 of these were diagnosed in newborns.

Clinical spectrum

The most common clinical presentation in pregnant patients with listeriosis is bacteremia. For unknown reasons, CNS infections, which are common in other populations at risk for listeriosis, are rare in pregnant individuals with listeriosis; they are often asymptomatic. Symptomatic pregnant patients often have a febrile illness similar to influenza with fever, muscle aches, and, occasionally, nausea or diarrhea during the bacteremic phase of the disease. Although the symptoms may be mild, listeriosis still can lead to premature delivery, infection of the newborn, or even stillbirth.

Placental transfer of the organism to the fetus can cause amnionitis, which usually results in either spontaneous septic abortion or premature labor with delivery of an infected baby. Fetal infection may manifest as septicemia, meningoencephalitis, or disseminated granulomatous lesions with microabscesses. Twenty-two percent of perinatal infections result in neonatal death or stillbirth. ^[24] Among those who have listeriosis during pregnancy, two thirds of surviving infants develop clinical neonatal listeriosis. Early diagnosis and antimicrobial treatment of infected individuals during pregnancy can lead to the birth of a healthy child.

In neonates, the mortality rate is approximately 50%. Mortality is more likely in early-onset neonatal sepsis. Late-onset listeriosis typically manifests as meningitis at 2-4 weeks of life.

Screening

Routine screening for Listeria is not recommended in pregnant individuals because carriage of these organisms in the vagina or gut is not thought to be associated with a predisposition for listeriosis in pregnancy. Blood cultures are the primary means of diagnosis, and results are more likely to be positive when the patient is febrile. In the neonate, Listeria can be cultured from meconium, nose or eye swabs, urine, cerebrospinal fluid, blood, placental tissue, or lochia.

CDC recommendations

Prevention mainly is achieved by educating pregnant people to avoid unsafe foods. The following are recommendations by the CDC for the general population:

• Thoroughly cook raw food from animal sources.

• Thoroughly wash raw vegetables before eating them.

• Keep uncooked meats separate from vegetables and cooked foods.

• Avoid unpasteurized milk or foods made from raw milk.

• Wash hands, knives, and cutting boards after handling uncooked foods.

• Consume perishable foods as soon as possible.

According to the FDA, it is recommended that the following cautions be taken when handling food:

• Rinse raw produce, such as fruits and vegetables, thoroughly under running tap water before eating, cutting, or cooking. Even if the produce will be peeled, it should be washed first.

• Scrub firm produce, such as melons and cucumbers, with a clean produce brush.

• Dry the produce with a clean cloth or paper towel.

• Separate uncooked meats and poultry from vegetables, cooked foods, and ready-to-eat foods.

The following are additional recommendations for high-risk patients (including pregnant patients):

• Avoid soft cheeses unless labels clearly indicate that they are made from pasteurized milk.

• Avoid spilling fluid from packages of hot dogs onto food preparation surfaces, cooked foods, vegetables, and ready-to-eat foods, and wash hands after handling hot dogs and deli meats.

• Do not consume hot dogs, deli meats, or cold cuts, unless they are heated and steaming hot.

• Do not consume refrigerated pates, meat spreads, or refrigerated smoked seafood.

Diagnosis

Confirming a diagnosis of listeriosis requires a culture showing L monocytogenes in blood or CSF. Serologic testing is unreliable for confirming a diagnosis, and stool cultures are not sensitive or specific.

Treatment/Management 

The dose of ampicillin is 2 g IV every 4 hours. Penicillin at 4 MU IV every 4 hours is an alternative. If the patient has a beta-lactam allergy, desensitization should be performed.

Alternatively, trimethoprim/sulfamethoxazole is the usual alternative for patients allergic to penicillin but, as described above, can be problematic during the first or third trimesters.

Early diagnosis and treatment are extremely important in preventing the potential effects of syphilis in pregnant individuals and their infants. Untreated primary or secondary syphilis in pregnant people leads to congenital syphilis in 40-50% of cases. In 2002, 451 cases of congenital syphilis were reported in the United States.

Lack of prenatal care and failure to properly diagnose and treat syphilis in the mother are the most important factors that lead to congenital syphilis amd should be the focus of preventive efforts.

Etiology

Syphilis is caused by Treponema pallidum, a helical, tightly coiled, motile spirochete.

Clinical spectrum

The stage of maternal disease during which the fetus is exposed to infection determines the morbidity risk; the earlier the stage of disease, the higher the risk of morbidity. Untreated primary or secondary syphilis in pregnancy leads to a fetal infection rate of almost 100%. Infection of the fetus before the fourth month of pregnancy is unusual. The disease can cause stillbirth, late abortion, neonatal disease, neonatal death, or latent infection. ^[6]

The clinical presentations of syphilis in pregnant people mirror those in nonpregnant people. In primary syphilis, a hard, painless red ulcer typically forms on the vulva, cervix, or vagina. Secondary syphilis predominantly manifests as a nonpruritic rash that may involve the palms and soles. Fever, lymphadenopathy, and joint pain are less common manifestations of secondary syphilis. The latent stage causes no symptoms, and, although the disease may not be transmitted to sexual partners, it still is transmissible to the fetus. One third of patients eventually may develop tertiary syphilis, which can result in cardiovascular or gummatous disease. Neurosyphilis can occur at any stage, resulting in CNS or ophthalmic presentations.

Screening

Even when syphilis is considered unlikely, routine antenatal screening is warranted for all pregnant individuals for prevention and surveillance. The earlier in pregnancy the treatment is provided, the more efficacious it is. Therefore, serologic tests should be performed at the initial prenatal visit. If the patient is considered high risk, tests should be repeated at 28 weeks' gestation and at delivery. ^[8]

Diagnosis

The nontreponemal antibody tests generally are used for screening. These tests, including rapid plasmin reagin and Venereal Disease Research Laboratory (VDRL) tests, are highly sensitive but nonspecific. Nontreponemal antibody test results often are false-positive in pregnant women; therefore, positive findings should be confirmed with specific antitreponemal antibody tests such as the microhemagglutination assay– T pallidum (MHA-TP) and the fluorescent treponemal antibody absorption test (FTA-ABS). Antitreponemal antibody test findings are not indicators of current infection because results may remain positive for life. In primary syphilis, the diagnosis can be confirmed by identifying T pallidum in dark-field examination of material taken from a lesion. Because most pregnant patients do not have visible lesions, serologic screening is the primary means of establishing the diagnosis.

Treatment/Management 

Once syphilis is diagnosed, consider other sexually transmitted diseases, especially HIV, while starting treatment. Treatment in pregnant patients is the same as in nonpregnantpatients, with a single dose of 2.4 million units of intramuscular benzathine penicillin for primary, secondary, and early latent syphilis, but some experts recommend a second dose of benzathine penicillin G 1 week after the initial dose, especially in the third trimester or in patients with secondary syphilis. In late latent syphilis, treatment consists of 3 doses of benzathine penicillin (as in nonpregnant women), each one week apart. If results of subsequent quantitative VDRL or an equivalent test show a 4-fold increase, re-treat the patient and perform a lumbar puncture to rule out neurosyphilis.

Penicillin is the only drug that can be used in pregnant patients with syphilis. Penicillin is used in pregnancy for syphilis, as it reaches higher optimal concentrations in the amniotic fluid, whereas other drugs of choice may not suffice in this amniotic space. Those who are allergic to penicillin must be desensitized and then treated with penicillin. Erythromycin may not prevent congenital syphilis, and the tetracyclines are not recommended in pregnant patients. Ceftriaxone and azithromycin have not been adequately studied in this context.

Using penicillin therapy in pregnant women with early syphilis can cause a Jarisch-Herxheimer reaction. In addition to the usual manifestations, pregnant women can present with uterine contractions, preterm labor, and premature delivery. However, these concerns should not delay necessary therapy.

For excellent patient education resources, visit eMedicineHealth's Sexual Health Center. Also, see eMedicineHealth's patient education article Syphilis.

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States and continues to be a major cause of complications in pregnancy and disease transmission in newborns. Although chlamydial infections can be easily treated and cured, they can have many consequences if left untreated. Of untreated women with chlamydial infection, 40% develop pelvic inflammatory disease (PID). Of these women, 20% become infertile, 18% develop chronic pelvic pain, and 9% have potentially life-threatening ectopic pregnancy.

Etiology

C trachomatis is a bacterium with a unique biphasic life cycle. The elementary body is an extracellular form that is necessary for transmission. Upon uptake into a host cell, differentiation into the reticulate body occurs, which is the replicative form. After binary fission occurs, daughter reticulate bodies transform into elementary bodies, which are then released from the cell.

Transmission

The usual mode of transmission to the fetus is vertical during the second stage of labor. The major routes of entry are the eye and the nasopharynx. Prenatal screening for chlamydia along with treatment of infected mothers is about 90% effective in preventing their infants from acquiring infection. ^[25]

Clinical spectrum

Approximately 75% of women with C trachomatis infection are asymptomatic. C trachomatis can cause endometritis, cervicitis, acute PID, and acute urethral syndrome in all women and chorioamnionitis, postpartum endometritis, and gestational bleeding in pregnant patients. The endometritis noted in these patients can be observed after delivery, and infection may be severe enough to necessitate hysterectomy. In neonates, C trachomatis infection commonly causes conjunctivitis (ophthalmia neonatorum) and pneumonia. Proper treatment of infected women can prevent these complications.

The contention that chlamydia may induce premature labor has been controversial, but infection has been found to lead to complications. ^[26] If a woman has symptoms of dysuria and frequency and urine culture results are negative, chlamydia is frequently the cause.

Screening

The CDC/US Preventive Services Task Force recommends that all pregnant women undergo screening early in pregnancy and that pregnant women younger than 25 years and high-risk patients undergo screening again in the third trimester. ^[9] Screening early in pregnancy increases the opportunity to improve the pregnancy outcome, whereas screening in the third trimester prevents transmission to the infant. Those pregnant women who are found to have chlamydia during the first trimester should be retested 3-6 months later. Screening methods are delineated below.

Diagnosis

Chlamydial cervicitis should be considered in the presence of a yellow or green vaginal discharge, greater than 10 polymorphonuclear leukocytes per high-power field, and bleeding or edema of the cervix. However, physical examination findings are completely normal in many infected women.

According to the CDC, the following are the accepted screening methods ^{[10, 11]} :

• A nucleic acid amplification test (NAAT) performed on urine or an endocervical swab specimen: NAATs have the highest sensitivity for these specimens

• An unamplified nucleic acid hybridization test, an enzyme immunoassay, or direct fluorescent antibody test performed on an endocervical swab specimen

• Culture performed on an endocervical swab specimen

Treatment/Management 

Azithromycin (1 g PO as a single dose) is considered safe and effective for treating urogenital chlamydial infections in pregnancy and is now the first-line recommended therapy. ^[12] Amoxicillin (500 mg PO 3 times per day for 7 d) is an alternative. Erythromycin is a second-line agent because of compliance-limiting GI adverse effects. Tetracyclines and fluoroquinolones are contraindicated in pregnant women. Retest treated women 3 weeks after therapy to ensure therapeutic cure, considering the serious consequences that can occur in mothers and neonates if infection persists during pregnancy.

Gonococcal infections cause no symptoms in approximately 50% of patients and thus warrant screening in pregnancy. Gonococcal infections are second only to chlamydial infections in the number of cases of bacterial STDs reported to the CDC. A pregnant woman with gonorrhea can transmit the infection to her infant at the time of delivery, causing life-threatening infections. Early detection and treatment lowers the likelihood of these complications.

Etiology

Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative diplococcus.

Transmission

Gonorrhea is transmitted vertically during the birth process. No evidence suggests placental transmission.

Clinical spectrum

Gonorrhea can infect the uterus, cervix, and fallopian tubes, leading to ectopic pregnancy and infertility.

During pregnancy, women with gonorrhea may be asymptomatic, although some reports have described manifestations of endocervicitis, early rupture of membranes, chorioamnionitis, septic abortion, intrauterine growth retardation, prematurity, and postpartum sepsis. However, the frequency of PID is reduced because upward passage of bacteria during pregnancy is prevented. Proctitis develops in up to 50% of women with gonorrhea and may be the only site colonized, necessitating rectal specimens for diagnosis if this is suspected. Patients with gonococcal pharyngitis frequently are asymptomatic, and the pharynx may be the only site colonized.

Newborns exposed to gonorrhea during vaginal delivery can develop an acute conjunctivitis known as ophthalmia neonatorum, sepsis, arthritis, and/or meningitis. The most important preventive measure for neonatal gonococcal infection is routine screening and treatment of pregnant women.

Disseminated gonococcal infection (DGI) is caused by bacteremic dissemination of N gonorrhoeae. Pregnancy is a predisposing factor to the development of DGI. The classic presentation of disseminated disease is an arthritis-dermatitis syndrome. The presenting symptom is often migratory polyarthralgia. The rash is vesicular and pustular, usually over the distal joints. Fever is common.

Screening

Because pregnant women with gonorrhea often are asymptomatic, screening is imperative for preventing complications. ^[11] The American College of Obstetricians and Gynecologists recommends screening (via endocervical culture) in only high-risk pregnant women on their first antenatal visit. The CDC recommends screening all pregnant women "at risk for gonorrhea" and recommends rescreening in the third trimester among those at continued risk. The recommended screening method remains endocervical culture. Alternatives include the NAAT and the nucleic acid hybridization test.

Diagnosis

Culture, nucleic acid hybridization, and NAAT tests can be used for diagnosis. A culture specimen should be taken directly from the endocervix onto Thayer-Martin media. Other sites, such as the pharynx, rectum, and urethra, also should be cultured as indicated. A Gram stain of the endocervical secretions should be performed when an immediate diagnosis is necessary. Gram-negative diplococci in polymorphonuclear leukocytes are diagnostic. Many NAAT tests are cleared for use in urine or vaginal swabs, in addition to endocervical samples.

Treatment/Management 

Gonorrhea treatment is complicated because N gonorrhoeae can develop resistance to antimicrobial therapies. ^[27] Quinolone-resistant N gonorrhoeae strains are widespread around the United States and the world. ^[28] Therefore, quinolones are no longer recommended for treatment of gonorrhea. ^[29] In any case, fluoroquinolones are contraindicated during pregnancy.

Cephalosporins are the class of antimicrobials recommended for gonorrhea treatment in the United States. The treatment of choice for uncomplicated cervicitis is ceftriaxone, administered as a single intramuscular (IM) injection of 250 mg, plus azithromycin, 1 g as a single oral dose. ^[30] Pregnant individuals who are allergic to cephalosporin can be treated with azithromycin 2 g PO once; spectinomycin 2 g IM is an alternative, but is not available in the United States.

Historically, all patients diagnosed with gonococcal infection have been recommended to also receive empiric therapy for C trachomatis. This recommendation still applies if chlamydial testing was not performed or if a test other than NAAT was used to test for chlamydial infection. However, the NAAT tests are sensitive enough for C trachomatis that patients with a NAAT test negative for C trachomatis at the time of gonococcal testing do not require empiric therapy for chlamydial infection.

Bacterial vaginosis is a clinical syndrome caused by excessive growth of bacteria that may normally be present in the vagina. The vagina normally is colonized with gram-positive, gram-negative, aerobic, and anaerobic bacteria. The dominant commensal found in the vagina is Lactobacillus, and the constitution of vaginal flora is altered by local pH changes.

In the United States, the rate of bacterial vaginosis in pregnancy is approximately 16%, with race playing an important determining factor. Of pregnant African-American women, 23% develop bacterial vaginosis, whereas 6% of pregnant Asian women and 4% of pregnant White women develop the disease. Infection can be transmitted via the placenta to the fetus and can cause intrauterine fetal death.

Etiology

The organisms responsible for causing bacterial vaginosis depend mainly on the pH of the vagina. With a pH of more than 4.5, Gardnerella vaginalis and anaerobes become the prominent associated organisms. The etiology is polymicrobial in nature and is associated with G vaginalis,Bacteroides species, Mobiluncus species, Peptococcus species, Ureaplasma urealyticum, and Mycoplasma hominis.

Clinical spectrum

Pregnant individuals with bacterial vaginosis may be asymptomatic or may report an abnormal vaginal discharge with an unpleasant, fishlike odor, especially after sexual intercourse. The discharge generally is white or gray, and patients may experience burning during urination or itching around the vagina.

The bacteria can ascend and colonize the amniotic membranes, decreasing the tensile strength of the membranes and causing the weakened membranes to rupture. G vaginalis infection can cause prostaglandin production and can lead to premature labor unresponsive to tocolytic therapy. In 1 study, 43% of pregnant patients with bacterial vaginosis went on to have a preterm labor.

Diagnosis

A diagnosis of bacterial vaginosis can be confirmed via clinical or Gram stain criteria. When using the clinical criteria, 3 of the following 4 conditions should be present:

• A homogenous, white, noninflammatory discharge that smoothly coats the vaginal wall

• Clue cells (ie, vaginal epithelial cells that have a stippled appearance due to aggregates of coccobacilli)

• Vaginal fluid pH of more than 4.5

• A positive whiff test result (ie, a fishy odor to the vaginal discharge before or after the addition of 10% potassium hydroxide solution)

When using Gram stain for diagnosis, determine the relative concentration of the bacterial morphotypes characteristic of the altered flora of bacterial vaginosis.

Modified screening criteria for developing countries recommend that only 2 of the 4 conditions need be met for a diagnosis of bacterial vaginosis. ^[31]

Screening

The US Preventive Services Task Force has determined that evidence is insufficient to warrant routine screening for bacterial vaginosis in pregnancy. The CDC suggests that women at high risk for premature labor (eg, women who have previously delivered a premature infant) should undergo screening at the first prenatal visit.

Treatment/Management

Treatment is the same as in nonpregnant patients, except that clindamycin cream should be avoided during the second half of pregnancy because it can increase the risk for premature birth and other adverse outcomes. Metronidazole at 250-500 mg orally twice per day for 7 days or clindamycin 300 mg orally twice per day for 7 days are recommended. Oral therapy is preferred for pregnant people because of the possibility of subclinical upper genital tract infection.

Evidence is insufficient to assess whether the treatment of asymptomatic pregnant patients with bacterial vaginosis who are at low risk for preterm delivery reduces adverse outcomes of pregnancy. ^[32]

Cautious use of antibiotics is especially important during pregnancy because they can affect both the mother and the fetus. Without exception, antimicrobials cross the placenta; thus, the fetus is exposed to the adverse effects of every antibiotic taken by the mother. Although prescription drugs account for less than 1% of all congenital malformations, potential teratogenic effects must be considered since antimicrobials are so commonly prescribed.

Classification

Very few data regarding the teratogenic potential of most antibiotics in humans are available. The US Food and Drug Administration has categorized all antibiotics according to the risks associated with their use in pregnancy. These categories are as follows:

• Category A: Studies in pregnant women do not demonstrate any risks to the mother or fetus.

• Category B: While animal studies show no risk, human studies are inadequate or animal toxicity has been noted, but the studies on humans show no risk.

• Category C: Animal studies indicate toxicity but studies in humans are inadequate.

• Category D: There is evidence of human risk.

• Category X: There have been reported fetal abnormalities in humans.

In all classes of drugs, the benefits of antibiotic use must always outweigh the risks.

Commonly used antibiotics

Commonly used antibiotics include the following:

• Penicillins (category B): Penicillin, amoxicillin, and ampicillin are the most widely used antibiotics in pregnancy because of their wide margin of safety and lack of known toxicity. In the collaborative perinatal project, 3546 women used penicillin during the first trimester, and no adverse effects were demonstrated. Because of increases in maternal intravascular volume and glomerular filtration rate, higher drug doses may be required to achieve the same serum levels achievable in nonpregnant patients.

• Cephalosporins (category B): This group has not been well studied in the first trimester and should therefore not be considered the first line of treatment in this stage of pregnancy. Generally, these drugs are considered safe.

• Sulfonamides (category C): Although these agents cause no known damage in utero, they can cause hyperbilirubinemia and kernicterus if the drug is still present in the neonate after birth. Therefore, they are typically avoided late in the third trimester. In mothers with G6PD deficiency, sulfonamide use has been associated with hemolysis. The combination of sulfonamides and trimethoprim in the first trimester has been associated with cardiovascular birth defects.

• Tetracyclines (category D): Tetracyclines have identifiable adverse effects in both the mother and the fetus. Pregnant women may sustain acute fatty necrosis of the liver, pancreatitis, and renal damage. In the fetus, these agents can cause growth stunting, discoloration of teeth, and hypoplasia of dental enamel. Although tetracyclines have not proven to be deleterious in the first trimester or in smaller doses, they are best avoided.

• Aminoglycosides (category D): Aminoglycosides used in the setting of hypomagnesemia and hypocalcemia or in conjunction with calcium channel blockers may cause neuromuscular blockade. Thus far, streptomycin and kanamycin are the only agents in the class with reported toxicity, associated with congenital deafness. Gentamicin (category C) has not been associated with congenital abnormalities, including deafness.

• Nitrofurantoin (category B): The collaborative perinatal project showed no increased risk for anomalies in 590 women who were exposed to the drug. In mothers with G6PD deficiency, it has caused hemolysis in both the mother and the fetus and should therefore be avoided in that setting.

• Quinolones (category C): Although animal studies have shown arthropathies, no human studies have been conducted and no cases of teratogenicity have been reported. These agents have a high affinity for bone and cartilage.

• Metronidazole (category B): Controversy has surrounded the use of metronidazole during pregnancy because of attributable mutagenicity in in vitro studies. However, human studies have shown no increase in congenital defects. Avoiding the drug during the first trimester is recommended, if possible.

• Macrolides (category B): These agents, including azithromycin, have not been associated with birth defects and are considered safe for use in pregnancy.

• Clindamycin (category B): This drug has not been associated with birth defects.

• Vancomycin (category C): No congenital abnormalities have been attributed to use of vancomycin based on limited data.