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ACOG Releases Report on Antimicrobial Therapy in Pregnancy
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Am Fam Physician. 1998 Oct 15;58(6):1477-1482.
The Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists (ACOG) has released a report titled “Antimicrobial Therapy for Obstetric Patients” (Educational Bulletin No. 245). The report summarizes current information on the use of antimicrobial therapy for intra-amniotic infection, endometritis, bacterial endocarditis, sexually transmitted diseases (chlamydial infection, gonorrhea, syphilis, vaginal trichomoniasis, bacterial vaginosis and herpes) and urinary tract infections. The following highlights information from the report.
The table on page 1478 summarizes the maternal and fetal effects of commonly used antibiotics. The report states that dosage modification may be needed during pregnancy because of the expanded maternal blood volume, increased glomerular filtration rate, increased hepatic metabolism and sequestration of the drug in the fetal compartment. According to the report, drug levels are generally 10 to 50 percent lower in women in late pregnancy and in the immediate postpartum period than in women who are not pregnant. When drugs are excreted primarily by the kidneys, dosages at the upper end of the recommended range may be needed.
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Passage of antimicrobial agents across the placenta and into fetal circulation is affected by the duration of the pregnancy and the protein-binding capacity of the drug. The report states that greater transfer occurs with advancing gestation and with agents that are minimally protein bound. For example, ampicillin, which is 20 percent protein bound, attains high levels in the fetus, whereas dicloxacillin, which is 98 percent protein bound, does not.
The report acknowledges that clinical trials of antibiotic therapy in pregnancy are insufficient to determine the safety of these agents with certainty. For agents such as azithromycin, acyclovir and the newer cephalosporins, no known or theoretic risks to the fetus exist. For other drugs, a theoretic risk exists but no untoward effects have been reported in humans. Sulfonamides have not been reported to cause neonatal kernicterus as a result of fetal exposure at any gestational age. Gentamicin and tobramycin have not been associated with hearing loss in neonates, but hearing loss has been reported in association with kanamycin and streptomycin. Fetal exposure to nitrofurantoin has not been reported to cause hemolytic anemia in the newborn, and metronidazole has not been associated with an increase in birth defects or subsequent cancer. The report states that use of these agents may be reasonable when they offer specific advantages over other agents.
All quinolone antibiotics are contraindicated in pregnancy because of reports of arthropathy in young animals receiving these agents. The report also mentions that information is scant on the use of newer extended-spectrum penicillins and second-, third-, and fourth-generation cephalosporins in pregnancy, but it is likely that these antibiotics are safe to use in pregnant women.
Infections Related to Pregnancy
The report states that most pelvic infections in women are caused by a mixture of aerobic and anaerobic organisms. Aerobic organisms include groups A, B and D streptococci, enterococci, Escherichia coli, Klebsiella species, Proteus species, Staphyloccus aureus and Gardnerella vaginalis. Anaerobic pathogens include Peptostreptococcus species, Prevotella bivia, Prevotella disiens, Bacteroides fragilis, Porphyromonas asaccharolyticus, Fusobacterium species, Clostridium species and Mobiluncus species. Other organisms include genital mycoplasmas, Chlamydia trachomatis and Neisseria gonorrhoeae.
Intra-amniotic Infection. According to ACOG, the most extensively studied regimen for amniotic infection is a combination of ampicillin, 2 g intravenously every four to six hours, or penicillin, 5 million U every four to six hours, plus an aminoglycoside such as gentimicin, 1.5 mg per kg intravenously every eight hours. This combination has excellent activity against group B streptococci and E. coli.
If cesarean delivery is required in a patient who has received ampicillin and gentamicin, the addition of clindamycin, 900 mg intravenously every eight hours, or metronidazole, 500 mg every 12 hours, is recommended immediately after the cord is clamped. As an alternative, newer agents such as cefotetan, ampicillin-sulbactam, ticarcillin with or without clavulanic acid, piperacillin with or without tazobactam and ceftizoxime provide good coverage and can be continued following cesarean delivery. Therapy should continue postoperatively until the patient has been afebrile and asymptomatic for 24 to 48 hours. After vaginal delivery, therapy may be discontinued soon after delivery.
Prophylaxis Against Postpartum Endometritis. The ACOG report states that the preferred agent for prophylaxis against postpartum endometritis is a first-generation cephalosporin such as cefazolin, 1 g intravenously, or ampicillin, 1 to 2 g intravenously. Cefazolin is noted to have the advantage of a longer half-life and less of a risk of allergic reactions, but it may more likely allow the emergence of enterococci in cases in which prophylactic therapy has failed. If an infection subsequently develops, the agent used in prophylaxis should not be used to treat the infection. Thus, the report states, extended-spectrum agents should not be used for prophylaxis but, instead, should be reserved for the treatment of endometritis.
Treatment of Postpartum Endometritis. The traditional regimen of a penicillin plus an aminoglycoside is usually effective when endometritis develops after vaginal delivery. Compared with endometritis after cesarean delivery, endometritis following vaginal delivery is much more likely to be caused by a single pathogen, such as streptococci. With cesarean delivery, the report notes that no regimen has been found to be superior to the standard regimen of gentamicin, 1.5 mg per kg, admixed with clindamycin, 900 mg, in the same intravenous solution, administered every eight hours. The addition of ampicillin may be warranted in specific circumstances, such as in patients with evidence of septic shock or when enterococcal infection is suspected.
Bacterial Endocarditis. Prophylaxis against bacterial endocarditis is not routinely recommended by the American Heart Association for patients with structural cardiac defects who undergo cesarean or vaginal delivery. It may be an option in high-risk patients. The recommended regimen is ampicillin, 2 g intramuscularly or intravenously, and gentamicin, 1.5 mg per kg (not to exceed 120 mg) within 30 minutes of delivery, followed in six hours by ampicillin, 1 g intramuscularly or intravenously, or amoxicillin, 1 g orally.
Common Infections in Pregnant Patients
Sexually Transmitted Diseases. For chlamydial infection, pregnant patients may receive one of the following treatments: erythromycin base, 500 mg, or erythromycin ethylsuccinate, 800 mg, orally four times daily for seven days; amoxicillin, 500 mg orally three times daily for seven days; or azithromycin, 1 g orally as one dose.
For gonorrhea, recommended treatment regimens include one of the following: ceftriaxone, 125 mg intramuscularly in a single dose; cefixime, 400 mg orally in a single dose; or spectinomycin, 2 g intramuscularly in a single dose (for patients who cannot tolerate a cephalosporin). In addition, treatment for chlamydial infection should be instituted because of the likelihood of coinfection.
For syphilis, a penicillin regimen appropriate for the stage of syphilis should be instituted. Patients with early syphilis should receive benzathine penicillin G, 2.4 million U intramuscularly. For late-stage syphilis, 2.4 million U intramuscularly should be administered once a week for three consecutive weeks.
Patients with vaginal trichomoniasis may be treated with 2 g of metronidazole orally in a single dose. Metronidazole is not recommended in the first trimester.
The ACOG report notes that recent studies suggest that treatment of bacterial vaginosis may reduce the rate of preterm delivery in certain high-risk patients. In the first trimester, symptomatic bacterial vaginosis can be treated with 2 percent clindamycin cream, one full applicator (5 g) intravaginally at bedtime for seven days, or oral clindamycin, 300 mg twice daily. Clindamycin cream is recommended instead of oral therapy because of the limited fetal exposure with vaginal administration. After the first trimester, metronidazole, 250 mg orally three times a day or 500 mg orally twice a day for seven days, may be used. Alternative therapy includes 2 g of oral metronidazole in a single dose or 300 mg of oral clindamycin twice daily for seven days.
The report states that little progress has been made in knowledge of the use of acyclovir for genital herpes infection in pregnancy. The decision to use acyclovir in a pregnant patient must be made on the basis of an individual's risk and benefit of therapy. Information is also insufficient on the use of acyclovir for recurrent episodes or for suppression throughout pregnancy. The agent has been used near term to prevent the need of cesarean delivery after a first episode of genital herpes.
Urinary Tract Infections. Treatment of asymptomatic bacteriuria should be considered when a urine specimen reveals 25,000 to 100,000 colonyforming units of a single organism per mL. A three-day course of antibiotic therapy, such as trimethoprim-sulfamethoxazole, nitrofurantoin or cephalexin, is sufficient for most women. Similarly, symptomatic cystitis can be treated with a three-day course of antibiotic therapy.
Effective regimens for acute pyelonephritis include one of the following: ampicillin, 1 to 2 g every six hours, plus gentamicin, 1.5 mg per kg every eight hours; ceftriaxone, 1 to 2 g every 24 hours; or trimethoprim-sulfamethoxazole, 160/800 mg every 12 hours. Intravenous therapy is continued until the patient is afebrile and is then followed by oral therapy to complete a 10-day course of therapy.
The report notes that women who develop pyelonephritis during pregnancy require antibiotic suppression and periodic screening for the remainder of the pregnancy. Women with other types of urinary tract infections likewise require periodic screening for infection with cultures or urine dipstick for nitrites or leukocyte esterase. If infection recurs, treatment should be initiated and the patient should receive suppressive therapy.
For more information on ACOG educational bulletins and committee opinions, contact ACOG at 409 12th St., S.W., P.O. Box 96920, Washington, D.C. 20090-6920; telephone: 800-762-2264.
Copyright © 1998 by the American Academy of Family Physicians.
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