LabMed

Pregnancy-Related Infections

At a Glance

Pregnancy-related infections discussed in this section include Group B streptococcal infections, urinary tract infections, isteriosis, influenza, and varicella. Infections due to these organisms are associated with increased morbidity or mortality of the mother and/or fetus.

Group B streptococcus (GBS; Streptococcus agalactiae) is a gram-positive coccus that is a frequent colonizer of the gastrointestinal (GI) and genital tracts. In pregnant women, GBS is associated with asymptomatic bacteriuria, urinary tract infections, and bacteremia. Pregnant women colonized with GBS may develop chorioamnionitis or pass the organism to the baby during birth, increasing the neonate's risk of infection. GBS bacteriuria is a marker for heavy GBS colonization in the genital tract.

Urinary tract infections in pregnancy range in severity from asymptomatic bacteriuria to pyelonephritis. Asymptomatic bacteriuria, which is defined as a positive urine culture in a patient without symptoms, has been associated with increased risk of preterm birth and perinatal mortality.

Listeriosis in pregnancy often presents as a nonspecific, influenza-like illness with fever, chills, and back pain. It most commonly occurs during the third trimester and can lead to preterm labor, neonatal infection, or fetal death. Listeriosis is associated with consumption of certain foods, such as cold cut meats or cheese. Although Listeria monocytogenes has a propensity for the central nervous system (CNS), meningitis due to Listeria is rare in pregnant women.

Pregnant women with influenza show a higher propensity to develop severe illness and die than the general population, based on data from previous circulating influenza strains, including 2009 H1N1. Prompt, accurate diagnosis and treatment are imperative.

Varicella pneumonia in pregnancy presents with cough, fever, and dyspnea. The clinical course may rapidly progress to respiratory failure. This entity is considered a medical emergency, as the mortality rate can exceed 40% in pregnant women.

Infections due to the TORCH organisms (i.e., Toxoplasma, rubella, cytomegalovirus, herpes simplex virus, and syphilis) acquired in utero or during the birth process cause considerable fetal and neonatal disease. The American College of Gynecology (ACOG) guidelines suggest obtaining rubella and syphilis serologies at the first prenatal visit. The major concern of TORCH testing relates to neonatal disease and is not further discussed in this section.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

GBS and urinary tract infections

Antepartum GBS screening in pregnant women can be performed by either culture-based or molecular-based methods. A vagino-rectal swab collected at 35-37 weeks gestation is held in enrichment broth for several hours and is then either cultured onto liquid or solid media or assayed by molecular means. In an effort to decrease the turn-around-time to recovery of the organism as compared to culture, molecular-based nucleic acid amplification tests (NAATs) can be run after broth enrichment for antepartum testing. However, the Centers for Disease Control and Prevention (CDC) recommended in their 2010 Guidelines for the Prevention of Perinatal Group B Streptococcal Disease that NAAT plays a limited role in intrapartum testing for GBS and could be considered in the limited circumstances of a woman at term with unknown colonization status and no other risk factors.Although molecular assays are faster than traditional culture, sensitivities of NAATs are not yet high enough to be performed directly on specimens without the enrichment step.

Pregnant women are also screened for asymptomatic bacteriuria at 12-16 weeks gestation. The screen is performed for GBS and other bacteria. Although past guidelines suggested screening for any amount of GBS in urine, it has recently been debated whether low colony count GBS bacteriuria contributes significantly to morbidity. The CDC 2010 Prevention of Perinatal GBS guidelines state that laboratories should report GBS in concentrations of greater than or equal to 104 (10,000) colony forming units (CFU)/mL in urine cultures. Once a pregnant patient is positive for GBS, repeat testing for clearance of the organism is not necessary because genital recolonization of GBS occurs despite treatment. The patient should thus be treated with antibiotics for GBS during vaginal delivery.

Other than GBS, organisms recovered from pregnant women with asymptomatic bacteriuria are similar epidemiologically to those from non-pregnant women. A screen is considered positive when either (1) two consecutive urine samples are positive for the same organism in counts greater than or equal to 100,000 CFU /mL or (2) one catheterized urine is positive for a single organism at a count greater than or equal to 100 CFU/mL.

However, laboratory practices in interpreting urine cultures vary, so clinicians must familiarize themselves with their particular laboratory’s cut-off values for positivity. Most laboratories result urine counts of less than 100 CFU/mL as negative and work up bacteria at counts greater than or equal to 10,000 CFU/mL. In women of childbearing age (which itself is variably defined across laboratories), certain bacteria at counts between 100 and 10,000 CFU/mL are identified and susceptibility tests performed.

Isolation of more than one genus or species of bacteria signifies potential contamination, as does isolation of Propionibacterium spp., viridans streptococci, or Lactobacillus spp. Rapid screening tests, such as urine dipsticks, should not be used in place of urine culture for detection of asymptomatic bacteriuria. Follow-up cultures after treatment should be obtained for bacteriuria with organisms other than GBS.

Listeria

Blood cultures should be collected when listeriosis is suspected. Listeria are short gram-positive rods, which may be mistaken on Gram stain or in the early phases of growth on culture plates for other bacteria, such as Corynebacterium spp. (diphtheroids, a common skin contaminant) or gram-positive diplococci (Streptococcus pneumoniae). Therefore, the clinician should maintain a high index of suspicion for Listeria in reports of gram-positive rods from blood cultures of pregnant patients. Analysis of cerebrospinal fluid (CSF) in listeriosis demonstrates pleocytosis with moderately high protein and low glucose concentrations. The CSF Gram stain is positive in only one-third of patients, as the organism is usually present in extremely low numbers.

Influenza

Laboratory diagnosis of influenza has evolved over the last several years. Molecular testing is the primary diagnostic method currently used, but rapid antigen testing, immunofluorescence, and rarely viral culture may also be performed. Table 1 summarizes the advantages and disadvantages of each method. Rapid influenza antigen detection tests (RIDTs) are assays that are used in clinical practice as point-of-care tests. Results are qualitative (negative or positive) and available generally within 15-30 minutes.

However, rapid antigen tests are much less sensitive (approximately 40%-70%; range 10%-85%) than molecular testing or viral culture. In addition, the specificities of rapid antigen tests drop at the beginning and the end of respiratory viral seasons.

Molecular techniques, such as real-time polymerase chain reaction (PCR), are very sensitive and specific and may yield rapid results. For these reasons, molecular testing is currently the preferred method of diagnosis. Results are available usually within 2-6 hours. However, due to financial and logistical reasons, some laboratories cannot run these tests on a random access basis (at the time that the specimen arrives in the lab) and must “batch” the specimens to run at specific times during the work shift, which extends the time to results. Various multiplex viral (and bacterial) molecular panels are currently available.

Immunofluorescence (IF) test results, including direct fluorescent antibody (DFA) staining, are generally available within 1-4 hours, depending on how frequently the laboratory runs the test. Sensitivity and specificity of DFAs are moderately high, and several specimen types may be used with this technique. Performance characteristics of IF depend on laboratory expertise and the quality of the specimen. Finally, viral culture has a long turn-around-time of 1 or more days, depending on the method used. Although not typically limited by specimen type, viral culture is not a clinically useful diagnostic method because of its long turn-around-time. (Table 1)

Varicella

Diagnosis of varicella pneumonia can be made by PCR of blood or bronchoalveolar lavage fluid. Although serology was the mainstay of laboratory diagnosis in the past, the turn-around-time is too long and is not clinically useful.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

The laboratory must be notified of a penicillin allergy in a pregnant patient with a culture positive for GBS. In such cases, clindamycin therapy may be warranted and a screen for inducible clindamycin resistance may need to be performed on the organism.

The proportions of clindamycin- and erythromycin-resistant GBS isolates have been increasing over the past 20 years. Currently, resistance among invasive GBS isolates in the United States ranges from 13%-20% for clindamycin and between 25 and 32% for erythromycin. Clinicians should refer to their hospital’s local antibiogram to determine the current resistance rates at their institutions when deciding on empirical antibiotic therapy for GBS infections.

For influenza testing, the sensitivity of many assays is dependent on collection of an adequate sample. In particular, immunofluorescence DFA testing requires the presence of epithelial cells to evaluate for virus.

What Lab Results Are Absolutely Confirmatory?

Isolation of GBS and Listeria spp. is confirmatory.

Positive influenza results by PCR or immunofluorescence are confirmatory. Most often, positive influenza results by the rapid antigen test are confirmatory. However, specificity of these assays drops at the beginning and end of respiratory influenza seasons and should be confirmed if positive. Since sensitivity by rapid antigen testing is poor, a negative result must be backed up by another method.

References

"American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee Opinion No. 485: Prevention of early-onset group B streptococcal disease in newborns". Obstet Gynecol. vol. 117. 2011. pp. 1019-27.

(Committee opinion on the prevention management of group B streptococcal disease and the role of laboratory diagnosis.)

Verani, JR, McGee, L, Schrag, SJ. "Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC)". Prevention of perinatal group B streptococcal disease--revised guidelines from CDC. 2010.

"MMWR Recomm Rep". vol. 59. 2010. pp. 1-36.

(Updated algorithms for group B streptococcal screening in pregnant women, clarification of the colony count threshold, expanded recommendations of laboratory testing for GBS identification.)

Church, DL, Baxter, H, Lloyd, T, Miller, B, Gregson, DB. "Evaluation of the Xpert® group B streptococcus real-time polymerase chain reaction assay compared to StrepB Carrot Broth™ for the rapid intrapartum detection of group B streptococcus colonization". Diagn Microbiol Infect Dis. vol. 69. 2011. pp. 460-2.

(Good sensitivity of the Xpert molecular assay in detection of GBS as compared to culture.)

Schwartz, J, Robinson-Dunn, B, Makin, J, Boyanton, BL. "Evaluation of the BD MAX GBS assay to detect Streptococcus group B in LIM broth-enriched antepartum vaginal-rectal specimens". Diagn Microbiol Infect Dis. vol. 73. 2012. pp. 97-8.

(Sensitivity of PCR assay for GBS on BD MAX platform as compared to culture.)

"Evaluation of rapid influenza diagnostic tests for influenza A (H3N2)v virus and updated case count—United States, 2012". Morb Mortal Wkly Rep. vol. 61. 2012. pp. 619-21.

(The CDC showed significant variation in the sensitivity of point-of-care rapid antigen diagnostic tests for influenza.)
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