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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Preterm Labor and Preterm Premature Rupture of Membranes
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11. Antibiotics
What about antibiotics for the patient in preterm PPROM?
Yes, in the setting of PPROM antibiotics have been shown to increase the latency period before delivery, decrease the incidence of chorioamnionitis and postpartum endometritis, and to reduce the incidence of neonatal sepsis.
In the largest study, “ORACLE I”, with almost 5,000 women with PPROM participating, erythromycin 250 mg po qid x 10 days significantly prolonged the latency interval to delivery, reduced the incidence of neonatal sepsis, and showed a trend towards improving the incidence of the composite outcome of neonatal death, neurologic injury, and chronic lung disease.
Though there is no clearly identified regimen, the Cochrane Library suggests that macrolide regimens may be safer, as they were less associated with an increased risk of necrotizing enterocolitis.
One could consider broad spectrum agents initially like erythromycin 250 mg I.V. q 6 hours for 48 hours, or ampillin 1-2 grams q 6 hours I.V. for 24 hours. The I.V. regimen should followed either by erythromycin 333 mg q 8 hours p.o. for 5 days, or azithromycin 1 gram p. o..
Treatment of asymptomatic women with bacterial vaginosis, recommended in the past, has not proven to be beneficial, except in a subset of African-American women with more than one prior preterm births . NB: Some studies have shown more preterm births in women treated with metronidazole, possibly due to a treatment associated release of proinflammatory bacterial products.
What about antibioticsfor the patient in preterm labor?
Current investigation has incriminated infection as a likely cause of at least a subset of “idiopathic” preterm labor. In studies of women with idiopathic PTL with intact membranes who underwent amniocentesis, 8-12 per cent had positive bacterial cultures. More significantly, various inflammatory cytokines, most prominently among them, interleukin-6 (IL-6), were elevated in the amniotic fluid of many more of these women, even if culture negative, and most of them went on to deliver quickly.
However, despite much evidence suggesting occult intrauterine infection as an important subset of PTL, antibiotic trials have been disappointing.
Eight RCTs involving erythromycin, ampicillin, and clindamycin, alone or in various combinations, have shown contradictory results as regards delay of delivery, and none has demonstrated an increase in birth weight or a decrease in mortality. NB: This was not true for women experiencing PPROM.
So, should antibiotics not be used for PTL with intact membranes?
Yes, certain antibiotics do have a specific role, and that is in the prevention of neonatal early onset group B streptococcal (GBS) infection. The 2002 CDC Guidelines suggest that women presenting with PTL or PPROM should have a vaginal and rectal culture for GBS collected on their initial assessment. They should then be empirically treated, preferably with penicillin.
The loading dose of aqueous penicillin G is 5.0 million units IV, followed by 2.5 million units IV q4h for 48 hours, or until the GBS culture is back. It is best to give penicillin piggy-backed into a fast flowing IV because, undiluted, it tends to cause a very unpleasant local burning sensation.
Ampicillin is a second choice because, with its broader spectrum, it may encourage the emergence of more resistant E.coli, the other leading neonatal pathogen. Remember to ask for sensitivities on isolates of patients with a history of penicillin allergy. Up to 20 per cent of GBS isolates are resistant to clindamycin and erythromycin, so those drugs unfortunately cannot be recommended empirically.
Women who have had only a minor drug reaction to penicillin (rash, itching) may be treated with cefazolin 1g IV q8h. Patients with a known history of anaphylaxis however will require vancomycin 500 mg IV q12h, unless sensitivies of the organism are known.
If the GBS culture is negative, the antibiotics may be stopped. If the culture is positive, antibiotics may be continued for 48 hours and then stopped. If the patient is a carrier and subsequently goes into active labor after her initial course of tocolytics and steroids, GBS prophylaxis should be resumed again intrapartum.
For a free case based CEU/CME module on Group B Streptococcal disease in the perinatal period with Clinical Pearls and Frequently Asked Questions go Here .
