This article is aimed at providing readers with a better understanding of several high risk pulmonary infections in pregnancy. These high-risk conditions are bacterial community-aquired pnewumonia (CAP), influenza, and varicella.
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ACEP News: Vol 32 – No 02 – February 2013Community Acquired Pneumonia
Incidence: The incidence of CAP [community acquired pneumonia] appears to be comparable to that in non-pregnant patients. However, if acquired, it can result in greater morbidity and mortality because of the physiologic adaptations of pregnancy. It is a leading cause of fatal non-obstetric infection in the pregnant patient. Pneumonia has been reported in 4.2% of antepartum admissions for non-obstetric illnesses.
Maternal Risks: The major factor predisposing pregnant women to severe pneumonic infections is an alteration in immune status. These changes occur primarily in cell-mediated immunity, making viral, fungal, and tuberculous infections particularly pathogenic in these women. As pregnancy progresses, functional residual capacity is decreased by 10% to 25%; which impairs maternal ability to tolerate respiratory disease. A history of asthma, or anemia with hemoglobin less than 10 gm/dl has been shown to increase the incidence of pneumonia significantly. Mortality (compared to that for nonpregnant patients) is higher for viral pneumonia but not as clearly shown for CAP. There may be a higher risk of progression to ARDS and sepsis. However, because of potential higher risk, CAP patients do require aggressive management.
Fetal Disease Course: Pneumonia can cause significant stress to the fetus. Preterm delivery and lower birth weight are risks. Maternal bacteremia can lead to fetal sepsis in some cases.
Clinical Picture: Pneumonia may be misdiagnosed up to 20% of the time due to the many physiologic and anatomic changes of pregnancy. Up to 76% of pregnant patients have underlying subjective dyspnea at 31 weeks. Lung auscultation can be unreliable due to atelectasis of pregnancy. Many patients attribute symptoms of pneumonia to pregnancy.
Diagnostic testing: Diagnostic testing are similar to non-pregnant patients as are listed in the IDSA CAP guidelines. Imaging includes chest X-ray with abdominal shielding as study allows.
Treatment: Prompt diagnosis and treatment with current antimicrobial therapy and intensive care unit management of respiratory compromise has reduced the maternal morbidity and mortality due to pneumonia in pregnancy. Prevention with vaccination in at-risk populations may reduce the prevalence and severity of pneumonia in pregnant women.
Bacterial Pneumonia: Antibiotics are comparable to those used in non-pregnant population as recommended in resources such as Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the management of community-acquired pneumonia in adults. This resource recommends fluoroquinolones such as moxifloxacin and gemifloxacin to be used in settings with high beta-lactam and macrolide resistance. The risk of teratogenicity is low, and fluoroquinolones can be given during pregnancy if indicated. Modifications in drug choice may be affected by changing local infection patterns.
Using usual hospital protocols for prompt antibiotic treatment plus avoiding delays in optimizing oxygenation are primary ways to improve maternal-fetal outcomes. Start empiric antibiotics initially directed at common causes of CAP, keeping in mind the local antibiotic resistance profile. In healthy pregnant women with no recent antibiotic exposure and no risk factors for drug resistant Strep. pneumoniae, a macrolide is recommended, per IDSA. In patients with comorbid conditions such as diabetes mellitus, alcoholism, chronic heart, lung, kidney, or liver disease, immunocompromised state, or use of antimicrobials in the past three months, a beta lactam plus a macrolide (strong recommendation; level I evidence) (High-dose amoxicillin [1 g 3 times daily] or amoxicillin-clavulanate [2 g 2 times daily] is preferred; alternatives include ceftriaxone, cefpodoxime, and cefuroxime [500 mg 2 times daily] OR use a respiratory fluoroquinolone such as moxifloxacin or levofloxacin.
Symptomatic Treatment: Since fever may pose risks to the fetus and newborn, pregnant patients should be encouraged to treat fever, with acetaminophen being an optimal choice. For cough, consider usual antitussive opiates, as well as bronchodilators for those with bronchospasm. However, there may be an association between 1st trimester pregnancy maternal opioid analgesic treatment and certain birth defects. This information should be considered by women and their physicians who are making treatment decisions during pregnancy.
Antihistamines that appear safe in pregnancy include: tripelennamine (PBZ, PBZ-SR), chlorpheniramine (generic), or hydroxyzine (generic, Atarax). Tripelennamine appears to have a very good experience record and may be a good first choice.
Ipratropium nasal spray (Atrovent® .03% for allergic rhinitis and .06% for colds) can be prescribed as 1-2 sprays each nostril bid to tid. It appears to be safe in pregnancy.
Coughing and rib injuries: Pregnant women appear to be at increased risk for rib injuries including fractures caused by coughing. The anatomical changes caused near term by the enlarging uterus on the lower rib cages predisposes to excess stress on these ribs during the large intrapleural cough pressures generated before the glottis opens. Treatment includes narcotic analgesics for pain and antitussive effects.
Hospitalization: Arrange inpatient treatment of pregnant women with pneumonia, if they meet severity criteria listed below. As respiratory compromise can affect fetus, consider conservative decision making for admission of any patient exhibiting any respiratory distress even without meeting these severity parameters.
- Respiratory rate 30 breaths/min or higher
- PaO2/FiO2 ratio 250 or less
- Temperature 39°C or higher or 36°C or lower
- Hypotension requiring aggressive fluid resuscitation
- Altered mental status
- Multiorgan dysfunction or septic shock
- Multilobar infiltrates
- Pulmonary cavitation
- Uremia
- Leukopenia (white blood cell count lower than 4,000 cells/mm3)
- Thrombocytopenia (platelet count lower than 100,000 cells/mm3)
Influenza
Note: Much of the information is based on current CDC recommendations. Physicians are encouraged to keep abreast of CDC recommendations
Vaccine: Indications: Injectable influenza vaccine should be considered for all pregnant women. The vaccine should be administered between mid-October and mid-November. Although not a common practice in the ED, any screening program for flu vaccine should put pregnant patients in highest priority group.
Nasal Spray Vaccine: Pregnant women should not receive the live nasal spray influenza vaccine, but family and household members and other close contacts of pregnant women (including healthcare personnel) who are 2 through 49 years old, healthy, and not pregnant may receive live nasal spray vaccine.
Contraindications: Same as in non-pregnancy. Pregnant women should not receive the live nasal spray influenza vaccine
Acute Infection: Clinical presentation is similar to the non-pregnant patient. Symptoms are usually self-limited, but complications should be anticipated if symptoms continue for longer than 5 days or if worsening clinical course. Influenza is usually a self limited infection, causing malaise, myalgias, fever, rhinorrhea, nausea, vomiting, cough, headaches, pharyngitis. Symptoms usually resolve within one week, though cough and malaise can persist beyond two weeks. The most common complication of influenza is pneumonia. Superimposed or secondary bacterial pneumonia develops two to fourteen days after influenza symptoms have resolved.
Testing : IIdeally, pregnant women who have suspected influenza infection should be tested for influenza. However treatment should be initiated based on clinical suspicion during influenza season. Reasons to avoid withholding treatment:
- significant rate of false negative rapid screens
- antivirals most effective within first 2 days of illness and still effective up to 4 days (see below).
Antiviral: As stated above, initiate treatment based on symptoms and local epidemiology. Also note that because influenza vaccination is not 100% effective in preventing influenza, a history of influenza vaccination does not rule out the possibility of influenza virus infection in an ill
patient with clinical signs and symptoms compatible with influenza.
Although zanamivir can be used in pregnancy, oseltamivir is preferred for treatment of pregnant women because of its systemic absorption. Theoretically, higher systemic absorption might suppress influenza viral loads more effectively in sites other than the respiratory system (e.g., placenta) and might provide better protection against mother-child transmission.
The drug of choice for chemoprophylaxis is less clear. Zanamivir may be preferable because of its limited systemic absorption; however, respiratory complications that may be associated with zanamivir because of its inhaled route of administration need to be considered, especially in women at risk for respiratory problems. For suspected influenza, oseltamivir treatment should be initiated as soon as possible – ideally within 48 hours of onset of symptoms. In addition, any pregnant woman hospitalized with confirmed, probable, or suspected infection should receive oseltamivir, even if more than 48 hours have elapsed since illness onset. Beginning treatment as early as possible is critical.
Antiviral treatment might still be beneficial in patients with severe, complicated or progressive illness and in hospitalized patients when given after 48 hours of illness onset. For example, antiviral treatment of pregnant women (of any trimester) with influenza A (2009 H1N1) has been shown to be most beneficial in preventing respiratory failure and death when started within 3 days of illness onset but still provided benefit when started 3– 4 days after onset compared to 5 or more days. A larger study reported similar findings and showed that starting oseltamivir treatment up to 4 days after illness onset provided benefit in reducing the risk of severe illness compared to later treatment of 2009 H1N1.
Dosing:
- Oseltamivir: 75 mg BID X 5 days for acute infection; Q day X 10 days for prophylaxis
- Zanamivir: Two 5-mg inhalations (10 mg total) BID X 5 days for acute infection; Q day X 10 days for prophylaxis
Risks in Pregnancy: During previous influenza epidemics and pandemics, pregnant women have appeared to suffer higher influenza-associated morbidity and mortality compared with women who are not pregnant. This is thought to be related to several physiologic changes that occur during pregnancy, including alterations in the cardiovascular, respiratory, and immune systems.
Pneumonia: Influenza can lead to a primary viral pneumonia with potential for a secondary bacterial pneumonia. Incidence has been reported in 12% of influenza infected pregnant women. Primary influenza pneumonia does not respond well to antiviral therapy, and mortality remains high. Consider admission of all pregnant patients with respiratory symptoms as well as confirmed pneumonia.
H1N1: Pregnant women who were otherwise healthy were severely affected by the 2009 H1N1 influenza A virus (formerly called “novel H1N1 flu” or “swine flu”). In comparison to the general population, a greater proportion of pregnant women infected with the 2009 H1N1 influenza virus had been hospitalized. In addition, severe illness and death had occurred in pregnant women, including a higher fatality rate compared to general population.
Symptomatic treatment: See discussion under CAP.
Risks to Fetus: Influenza infection increases risk of preterm labor and spontaneous abortion. Fetal distress associated with severe maternal illness can occur.
Patient Education: Web information for patients to be downloaded include:
- For seasonal flu vaccine: http://www.cdc.gov/flu/about/qa/fluvaccine.htm
- For general flu: http://www.marchofdimes.com/pnhec/188_10596.asp
Pregnant women appear to suffer higher influenza-associated morbidity and mortality compared with women who are not pregnant. This is thought related to physiologic changes.
Varicella
The two scenarios most likely to confront an emergency physician are (1) a patient with varicella exposure and no symptoms, and (2) a patient with active infection. Although the focus of this paper is acute pulmonary disease, dealing with prevention of pneumonia is deemed important.
Exposure: Birth in the United States before 1980 is considered evidence of immunity except for health-care personnel (HCP), pregnant women, and immunocompromised persons. For these three groups, certainty regarding immunity is desirable because of the possibility of nosocomial transmission to high-risk patients; transmission of the virus to the fetus, which might result in congenital varicella syndrome; and the possibility of severe disease.
Pregnant women appear to be at higher risk for severe varicella and complications. Therefore, those exposed without definitive immunity should be strongly considered for varicella zoster immune globulin (VZIG). Administration of VZIG to these women has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella. Thus, the primary indication for VZIG in pregnant women is to prevent complications of varicella in the mother rather than to protect the fetus. Neonates born to mothers who have signs and symptoms of varicella from 5 days before to 2 days after delivery should receive VZIG, regardless of whether the mother received VZIG. In this situation be sure to communicate this information to the physician who will be caring for the newborn.
For a woman with unknown immune status, serologic serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, varicella zoster immunoglobulin should be administered.
Limited data suggest that the incidence of varicella is comparable among persons who receive varicella zoster immune globulin within 4 days of exposure and those who receive it more than 4 days (up to 10 days) after exposure, and attenuation of disease might be achieved with administration of varicella zoster immune globulin up to 10 days after exposure.
One study indicated an increase in varicella incidence with increasing time between exposure and administration of the immune globulin, but disease was attenuated in all cases. VariZIG can be obtained by healthcare providers from the sole authorized U.S. distributor, FFF Enterprises
(Temecula, California), by calling 800-843-7477 at any time or by contacting the distributor online at www.fffenterprises.com. As with any product used under an IND protocol, patients must give informed consent before receiving the product.
Active infection: Varicella pneumonia occurs in 10% of pregnant patients with VZV. Risk factors include smoking, advanced gestation and greater than 100 pox skin lesions.
Women with varicella infection in pregnancy should be treated with oral antiviral agents (e.g., acyclovir 800 mg 5 times daily). In cases of progression to varicella pneumonitis, maternal admission to hospital should be seriously considered. Intravenous acyclovir can be considered for severe complications in pregnancy (oral forms have poor bioavailability). The dose is usually 10 to 15 mg/kg of BW or 500 mg/m2 IV every 8 hours for 5 to 10 days for varicella pneumonitis, and it should be started within 24 to 72 hours of the onset of rash.
Neonatal health care providers should be informed of peripartum varicella exposure in order to optimize early neonatal care with varicella zoster immunoglobulin and immunization. Varicella zoster immunoglobulin should be administered to neonates whenever the onset of maternal disease is between 5 days before and 2 days after delivery.
Vaccine: Varicella vaccine is not to be given during pregnancy but reserved for non-immune patients after delivery, delayed 5 months after VZIG administration.
Patient information: Chickenpox and Pregnancy: www.cdc.gov/ncbddd/pregnancy_gateway/infections-chickenpox.html
Dr. Howard Roemer is an adjunct associate professor in the Department of Emergency Medicine at the OU School of Community Medicine, Schusterman Center, Tulsa, Okla.; Dr. Benjamin Roemer is an emergency physician at Northwest Medical Center in Tucson, Ariz.; Dr. Katz is a clinical professor in the Department of OB-GYN at Oregon Health Sciences University and medical director for women’s services at Sacred Heart Medical Center for Genetics and Maternal-Fetal Medicine, Eugene, Ore.; Dr. Dewan is a physician infectious diseases and chair of the Infection Control Committee/Antibiotic Stewardship Program, at the Normal Regional Health System, Norman, Okla.; and Mr. Bentley is a pre-medical student.
[For the list of references, visit our online version of this article availabe at www.acepnews.com]
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