Infections in Pregnant Women
Infectious diseases commonly manifest during pregnancy, ranging from benign to life-threatening conditions. Many of these women will present in the acute care setting. Occasionally, symptoms of pregnancy and disease may overlap, making it difficult to accurately diagnose gravid women. In addition, pregnancy is an immune-altering state, which in certain circumstances affects the management of pregnant women as compared with nonpregnant counterparts. It is crucial that in obstetric triage units and emergency room settings providers are able to diagnose and appropriately treat pregnant women.
Clinical intra-amniotic infection (IAI) or chorioamnionitis complicates 1% to 4% of all births (Gibbs & Duff, 1991). The major risk factor for IAI in the obstetric triage setting will be rupture of the amniotic membranes. Although chorioamnionitis with intact membranes does occur, it is less common and may be due to Listeria monocytogenes, Group B Streptococcus (GBS), or recent obstetric procedures such as cerclage or amniocentesis (Creasy et al., 2014; Tita & Andrews, 2010). Although IAI is more commonly seen during labor, these women may primarily present to the obstetric emergency room. Because of the potential for maternal and neonatal sepsis and death, in pregnant women with fever and other supporting symptomatology, IAI must be considered until proven otherwise.
The presenting symptoms of chorioamnionitis may overlap with other diagnoses seen more commonly in the emergency setting in nonpregnant women, such as pyelonephritis. Most women with chorioamnionitis will have ruptured membranes; therefore, leakage of fluid and contractions may be frequent complaints. To differentiate from normal labor, fever, constant abdominal pain, foul-smelling discharge, general malaise, and/or body aches are noted. In rare circumstances, IAI can be present in women with intact membranes. To make the diagnoses of IAI in a pregnant woman, a high index of suspicion is necessary when a patient presents with signs of infection and abdominal pain.
284HISTORY AND DATA COLLECTION
A thorough history is recommended. A focus on pregnancy-related symptoms such as leakage of fluid and contractions, any recent procedures, or exposure to foodborne pathogens such as L. monocytogenes can be elicited. Listeriosis is 18 times more common in the pregnant population versus the nonpregnant population, and transmission is through ingestion of contaminated foods such as unpasteurized milk and soft cheeses, unwashed meat and vegetables, and processed foods such as deli meat and hot dogs (Lamont et al., 2011). Prevention of listeriosis can be achieved by thoroughly washing all raw fruits and vegetables, thoroughly cooking all meat and poultry, and avoidance of high-risk items such as unpasteurized dairy, deli meats or hot dogs (unless steaming hot), and smoked seafood (unless canned) (Centers for Disease Control and Prevention [CDC], 2014b).
The diagnosis of IAI is usually made on the basis of clinical symptoms. Chorioamnionitis is diagnosed by the presence of fever (>100.4°F) and one or more of the following: uterine tenderness, maternal or fetal tachycardia, maternal leukocytosis, and foul-smelling/purulent discharge (Gibbs, Dinsmoor, Newton, & Ramamurthy, 1988; Tita & Andrews, 2010).
LABORATORY AND IMAGING STUDIES
Amniotic fluid testing, using rapid markers (Gram stain, cell count, glucose, and leukocyte esterase), may be used when considering delivery of a preterm or nonviable fetus when the diagnosis of chorioamnionitis is unclear. A positive Gram stain, low glucose (<15 mg/dL), or elevated white blood cell (WBC) count (>30/mm3) may be indicative of infection (Romero et al., 1993). Amniotic fluid culture would be of low yield because of the time it takes for obtaining results.
Chorioamnionitis may present with a wide range of symptoms. It varies from vague symptoms, such as abdominal pain or malaise, to acute pain with signs of peritoneal irritation. The differential diagnoses include pyelonephritis, gastroenteritis, appendicitis, and preterm labor.
CLINICAL MANAGEMENT AND FOLLOW-UP
The mainstay of treatment in the setting of chorioamnionitis is immediate antibiotic therapy and delivery. Chorioamnionitis alone is not an indication for cesarean delivery. Antepartum treatment with antibiotics decreases the risk of neonatal sepsis and mortality, and so it must be initiated without delay (Gibbs et al., 1988). IAI is usually polymicrobial in nature, and a broad-spectrum antibiotic is recommended; however, the optimal regimen is not well established. A Cochrane Review published in 2014 failed to identify the most appropriate antibiotic regimen for patients with IAI (Chapman, Reveiz, Illanes, & Bonfill Cosp, 2014). A commonly used regimen is ampicillin every 6 hours and 285gentamicin every 8 hours until delivery. Other regimens, such as those using extended-spectrum penicillin (e.g., ampicillin plus a beta-lactamase-inhibitor, such as sulbactam), may be equally as effective, but have not been compared with standard agents (Creasy et al., 2014). The optimal length of antibiotic treatment postpartum is unknown and varies from one dose of antibiotics after delivery to treatment for 24 to 48 postpartum hours (Chapman et al., 2014; French & Smaill, 2004; Hopkins & Smaill, 2002). If a cesarean delivery is performed, clindamycin 900 mg every 8 hours (or metronidazole) may be added for additional anaerobic coverage (Tita & Andrews, 2010). Acetaminophen for fever may also be administered, not to exceed the maximum dose of 4 g/d.
Isolated maternal fever (“documented” fever)
Maternal oral temperature 39.0°C (102.2°F) on any one occasion is documented fever.
If the oral temperature is between 38.0°C (100.4°F) and 39.0°C (102.2°F), repeat the measurement in 30 minutes; if the repeat value remains at least 38.0°C (100.4°F), it is documented fever.
Suspected Triple I
Fever without a clear source plus any of the following:
• Baseline fetal tachycardia (greater than 160 beats per min for 10 min or longer, excluding accelerations, decelerations, and periods of marked variability)
• Maternal white blood cell count greater than 15,000 per mm3 in the absence of corticosteroids
• Definite purulent fluid from the cervical os
Confirmed Triple I
All of the previous items plus:
• Amniocentesis-proven infection through a positive Gram stain
• Low glucose or positive amniotic fluid culture
• Placental pathology revealing diagnostic features of infection
Source: Adapted from Higgins et al. (2016).
Historically, the threshold for labeling a patient as having chorioamnionitis has been fairly low, for example, in the presence of maternal fever alone. This may not necessarily take into account the resultant neonatal interventions, which in many institutions involve routine neonatal intensive care unit observation and/or the administration of antibiotics. Thus, recently, a change in terminology has been recommended in order to better characterize cases as “isolated maternal fever” or “intrauterine infection, inflammation, or both (Triple I).” The features of isolated maternal fever versus suspected or confirmed Triple I are presented in Table 24.1 (Higgins et al., 2016).
During seasonal influenza outbreaks and influenza pandemics, most recently the H1N1 pandemic of 2009 and 2010, pregnant women are at a greater risk of hospitalization and death from complications of influenza (Siston et al., 2010). The influenza virus is an RNA virus, with three main types: A (most common), B, and C. It is easily transmitted through respiratory droplets, with an incubation period of 2 to 4 days (Cox & Subbarao, 1999). Once a woman is infected, she will remain infectious from about 1 day before the start of symptoms until approximately 1 week after becoming ill (CDC, 2016c).
Pregnant women presenting with influenza may have a fever (>100.4°F), cough, dyspnea, sore throat, runny nose, body aches, headache, fatigue, vomiting, or diarrhea. All or some of the symptoms may be present, and not all women will have a fever.
HISTORY AND DATA COLLECTION
A complete history includes the length, type, and severity of symptoms. A vaccination history, infectious contacts, and history of comorbidities including asthma, diabetes, and hypertension are also critical to assist in diagnosis. Pregnant women with asthma or chronic hypertension are more likely to require admission to an intensive care unit (ICU) with influenza complications, and so these women must be clearly identified (Siston et al., 2010; Varner et al., 2011).
A complete physical examination must be performed with attention to the presenting symptoms. Findings may include throat erythema, runny nose, wheezing, rales/rhonchi, tachypnea, and tachycardia. Fetal tachycardia may also be present with maternal fever.
LABORATORY AND IMAGING STUDIES
A rapid influenza test (types A and B) has been recommended in pregnant women if influenza is suspected. However, because of low sensitivity of the rapid tests, confirmation of negative tests may be performed with viral culture or reverse transcription polymerase chain reaction (RT-PCR; Harper et al., 2009). In the absence of a positive test, treatment is indicated if clinical suspicion is high. If there is uncertainty in the diagnosis, a complete blood count with a differential may help to determine if a bacterial infection is present versus influenza. A shielded chest radiograph is indicated if there are respiratory symptoms, such as dyspnea and findings consistent with pneumonia.
The differential diagnoses include a variety of other respiratory illnesses. Pneumonia, pharyngitis, the common cold, sinusitis, or bronchitis must all be considered.
CLINICAL MANAGEMENT AND FOLLOW-UP
Pregnant women suspected of having influenza in the obstetric triage setting need to be offered treatment with antivirals and acetaminophen if febrile or in the presence of myalgias (Fiore et al., 2011). Rest and hydration (either oral or intravenous) are also suggested. Oseltamivir (Tamiflu) is recommended by the CDC for use in pregnant women at a dose of 75 mg twice daily for 5 days. To 287improve maternal outcomes, treatment initiated within 48 hours of symptom onset is ideal. Early initiation of oseltamivir for pregnant women admitted to the hospital with laboratory-confirmed influenza is associated with reduced length of stay, especially in women with severe disease (Oboho, 2016). For women who respond to antipyretics and have no respiratory compromise, outpatient management may be appropriate. A follow-up visit with a care provider is recommended within 24 to 48 hours.
Hospitalization is recommended for pregnant women who are unable to tolerate oral intake, have fever unresponsive to acetaminophen, or have respiratory compromise. If a superimposed bacterial pneumonia is suspected, the most common organisms are Streptococcus pneumonia, Staphylococcus aureus, Haemophilus influenza, and Group A Streptococci. Empiric therapy with ceftriaxone and azithromycin, for example, may be appropriate (Mandell et al., 2007).
Sepsis is rarely diagnosed in pregnancy; however, its frequency in the United States is increasing, from 1 in 15,385 in 1998 to 1 in 7,246 in 2008 (Bauer, Bateman, Bauer, Shanks, & Mhyre, 2013). In 2001, the International Sepsis Definitions Conference defined sepsis as a systemic inflammatory response syndrome (SIRS) in the presence of infection. There are varying degrees of sepsis, which are defined clinically and described in Table 24.2 (Levy et al., 2003). Of note, there are no well-established criteria for sepsis in pregnancy, though research is ongoing. Lappen, Keene, Lore, Grobman, and Gossett (2010) demonstrated that neither the SIRS nor Modified Early Warning score (MEWS) were able to identify patients at risk of sepsis or death in the setting of IAI. In contrast, Oliveira-Neto et al. (2012) showed that the Sequential Organ Failure Assessment (SOFA) score performed well in its ability to predict the severity and prognosis in cases of severe maternal morbidity admitted to an obstetric ICU. Another tool, the Sepsis in Pregnancy Score (S.O.S.), was developed by modifying validated scoring systems including the Rapid Emergency Medicine Score (REMS) and the Acute Physiology and Chronic Health Evaluation (APACHE II), in accordance with recognized physiologic changes of pregnancy (Albright, Ali, Lopes, Rouse, & Anderson, 2014). The S.O.S. reliably identified patients at high risk for admission to the ICU in a retrospective cohort of 850 women evaluated in the emergency room. Prospective validation is pending.