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95 Pregnancy and the puerperium: infectious risks
Infectious diseases that occur during pregnancy and the puerperium pose special risks to the mother, fetus, and infant. Any intervention must be weighed against possible side effects.
Urinary tract infections
For pregnant women it is recommended to culture urine at the first prenatal visit. Treatment should be provided if the urine culture is positive.
Short courses (3 days) of antimicrobial therapy are usually effective in eradicating asymptomatic bacteriuria. Penicillins, cephalosporins, aztreonam, ertapenem, imipenem, and meropenem are considered safe. Sulfonamides, including TMP–SMX, are avoided in the first trimester and near term (because of kernicterus).
Recommended regimens include amoxicillin, 500 mg orally three times a day; amoxicillin–clavulanate, 875 mg twice a day; nitrofurantoin, 100 mg every 12 hours; sulfisoxazole, 500 mg three times a day; cephalosporins, such as cefuroxime–axetil, 250 to 500 mg every 12 hours, or cefpodoxime, 100 mg every 12 hours, can also be used. Fosfomycin, 3 g PO as a single dose, was shown to be effective when compared with other drugs administered for a longer time.
Urine culture should be performed 1 week after therapy and monthly until the end of pregnancy. Suppressive therapy until delivery is recommended for women who have persistent bacteriuria after two or more courses of therapy.
In acute cystitis, pyuria is found in most patients, and urine culture should be performed. Patients should be treated for 3 to 7 days if symptoms suggesting pyelonephritis are absent. The same antibiotic regimens suggested for asymptomatic bacteriuria can be utilized. Quinolones are contraindicated in pregnancy. Follow-up urine culture should be obtained 1 week after therapy. For recurrent infections, antimicrobial prophylaxis should be considered for the duration of pregnancy.
When acute pyelonephritis is the presumptive diagnosis, we admit pregnant patients to the hospital, culture urine and blood, and treat with intravenous antibiotics until the patient is afebrile for 24 hours. Then, oral therapy can be used to complete 10 to 14 days of therapy. If fever and symptoms persist >48 hours after treatment imaging studies of the urinary tract and repeat urine culture should be obtained. Antibiotic prophylaxis should be considered in patients with recurrent pyelonephritis, with periodic urine cultures for the remainder of the gestation.
Empiric treatment of acute pyelonephritis includes the following: ceftriaxone, 1 g IV every 24 hours, ceftazidime, 2 g IV every 8 hours, cefepime, 2 g IV every 12 hours, piperacillin–tazobactam, 4.5 g IV every 8 hours, ertapenem, 1 g IM every 24 hours, meropenem and aztreonam, 1 to 2 g IV every 8 hours. We avoid aminoglycosides whenever possible.
Premature rupture of fetal membranes and intra-amniotic infection
Premature rupture of fetal membranes (PROM) can occur at any time before uterine contractions and labor start. Subclinical infection or inflammation of the chorioamniotic membranes causes an important proportion of cases. Intra-amniotic infection (IAI), present in 40% to 75% of women with PROM, is the infection of the membranes, the amniotic fluid, the placenta, and/or the uterus. It is associated with a 50% rate of preterm deliveries before gestation week 30.
Maternal fever and tachycardia and fetal tachycardia are common manifestations of IAI. Maternal leukocytosis is common. Maternal bacteremia occurs in up to 10% of cases but is more common when virulent organisms (Escherichia coli 15%, group B streptococcus 18%) are causing the infection. Abnormal labor, necessity for C-section, hemorrhage, wound infection, and endometritis are maternal complications. Fetal and neonatal complications include sepsis, pneumonia, respiratory distress, intraventricular hemorrhage, and low apgar score.
When IAI is suspected amniocentesis is performed. Amniotic fluid is obtained for aerobic (group B streptococcus, E. coli, enterococci) and anaerobic (Peptostreptococcus, Bacteroides, and Fusobacterium species, Gardnerella vaginalis, and Mobiluncus species) cultures. Samples for Gram stain (48% sensitivity, 99% specificity), glucose level (sensitive when below 15 mg/dL), white blood cell count (above 30/mm3), and leukocyte esterase activity (trace or greater) and measurement of amniotic fluid cytokines (interleukin [IL]-1a, IL-6, IL-8, and tumor necrosis factor [TNF]) can be obtained at the same time. Antibiotics are used immediately. Ampicillin, 2 g IV every 6 hours, plus gentamicin, 5.1 mg/kg once daily, continued for 1 dose after delivery; clindamicin, 900 mg IV every 8 hours, can be added after cord clamping in cesarean deliveries to reduce endometritis. Alternatives include ampicillin–sulbactam, 1.5 to 3 g every 6 hours; or piperacillin–tazobactam, 3.375 to 4.5 g every 6 hours. For serious infections due to resistant bacteria, such as extended-spectrum β-lactamase-producing gram negatives, carbapenems (meropenem, doripenem, ertapenem) can be substituted.
Mycobacterial infection in pregnancy
The diagnosis and treatment of pregnant women with active tuberculosis (TB) follows the same steps as in the nonpregnant individual. A human immunodeficiency virus (HIV) serology is mandatory. PPD is safe and accurate during pregnancy. Provided no multidrug resistance is suspected, the initial regimen consists of isoniazid (with pyridoxine 50 mg/day), rifampin, and ethambutol, for 2 months, followed by rifampin and isoniazid for 7 months. Isoniazid may exhibit increased maternal liver toxicity during pregnancy. Pyrazinamide is not currently recommended in the United States for routine use. Expert consultation is advised.
Therapy for latent TB infection (LTBI) may be started even during the first trimester, with isoniazid (5 mg/kg/day, maximum 300 mg) for 9 months (supplemented with pyridoxine) or rifampin (600 mg/day) for 4 months. Breastfeeding is not discouraged.
In pregnant AIDS patients, the treatment of disseminated disease due to Mycobacterium avium complex (MAC) is difficult. Azithromycin (Food and Drug Administration [FDA] category B) is the preferred macrolide for MAC prophylaxis and treatment (see Chapters 157, Tuberculosis, and 158, Nontuberculous mycobacteria). Again, expert consultation is advised.
Malaria and pregnancy
Pregnant women are more vulnerable to high parasitemia, severe infection, and mortality; fetuses are more vulnerable to low birth weight (LBW), prematurity, stillbirth, congenital disease, and death. Hence, exposure to malaria should be avoided, and diagnosis and treatment of identified cases should be prompt.The geographic distribution of drug-resistant malaria parasites, the clinical features in obstetric patients, and the laboratory diagnosis are the same as described in Chapter 200, Malaria. We recommend hospitalization for all pregnant women with malaria. All antimalarial drugs have potential fetal toxicity. Chloroquine phosphate, the blood schizonticide of choice for oral prophylaxis (500 mg [300 mg base] once a week beginning a week prior to potential exposure and continued for 4 weeks afterwards) and therapy (1 g [600 mg base] stat, and then 500 mg in 6 hours and 500 mg daily for two doses) is generally considered safe and is effective for treatment of plasmodial species other than chloroquine-resistant Plasmodium falciparum. Pregnant women should receive chloroquine once a week until the end of pregancy when primaquine can be administered to eradicate dormant hypnozoites that may be in the liver. Mefloquine appears safer than other antimalarial drugs, but concerns remain about stillbirth, LBW, and neuropsychiatric and cardiac side effects. Tetracyclines are contraindicated during pregnancy, but IV clindamycin (10 mg/kg followed by 5 mg/kg every 8 hours) is an alternative. Artesunate plus clindamycin is indicated during any trimester of pregnancy; for treatment in the second or third trimester, an artemisinin-based combination regimen known to be effective in the region of acquisition of malaria may be preferable. Atovaquone (250 mg) combined with proguanil (100 mg) is highly effective against chloroquine- and mefloquine-resistant P. falciparum malaria, but data in pregnancy are scarce. Rescue has been successful with atovaquone–proguanil combined with artesunate in multidrug-resistant P. falciparum infections without recorded toxicity. Small studies suggest that artemisinin-derived antimalarials are well tolerated. Quinine sulfate or quinidine gluconate with or without clindamycin are alternative regimens that require continuous monitoring of vital signs, blood glucose, and electrocardiogram (ECG). For severe malaria in the second and third trimester, parenteral artesunate is preferred over quinine/quinidine. Treatment should be started immediately with the most readily available drugs. Exchange transfusions might be added in severe malaria during pregnancy, but their benefit is controversial.
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