Group B Streptococcus (GBS) in Pregnancy: Hold the Vancomycin?
Far many more babies become “colonized” at delivery than ever go on to develop serious complications. The reason for this is unclear but it is probably a function of the extent of maternal colonization, the ‘quality’ of the maternal immune response to the organism (and the degree to which maternal antibody has been transferred to the fetus), and the gestational age of the baby (although serious infections can occur at any gestational age, premature babies are highly susceptible). About two-thirds of serious GBS infections are apparent at the time of delivery and 90% of babies who will develop complications do so within the first 48 hr after delivery. This is generally referred to as “early-onset” GBS infection and technically is used to define disease occurring in the first week of life. “Late-onset” disease affects another 10% of newborns, often presents as meningitis with septicemia, and rarely occurs after one month of age. Up to one-third of the survivors of GBS meningitis will develop long-term physical and/or neurological handicaps and in 1 of every 8 of these babies, the handicaps will be severe.
Because of the high morbidity associated with neonatal GBS infections, the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the Centers for Disease Control (CDC) endorse routine screening of all pregnant women for GBS at 35-37 weeks’ gestation, and prophylactic antibiotic treatment at the time of labor in those found to be colonized with GBS. Screening is performed by swabbing the lower vagina and rectum and culturing for the organism on ‘selective’ media. GBS may come and go, but a negative test within 5 weeks of delivery has a ‘negative predictive value’ of about 95%. This implies that only 5% of women are likely to acquire GBS between the time of screening and delivery. Interestingly, if GBS is detected at routine screening, the ‘positive predictive value’ of the bacteria actually being found at delivery is only about 87%.
The goal of prophylactic antibiotic therapy is to deliver antibiotics to the mother early enough in the course of labor that sufficient drug can be transferred across the placenta to achieve protective levels in the baby prior to birth. That means, the antibiotic selected must not only be able to kill GBS, but it must also be able to cross the placenta. Fortunately, GBS has not yet been found to have developed resistance to the antibiotic of choice, penicillin G, and this drug also readily crosses the placenta. It also has a long and proven safety record for the baby. Ideally, antibiotic therapy is begun, intravenously, at least 4 hr prior to delivery so that at least one or two doses can be administered before the baby is born.
Unfortunately, about 12% of the population report “allergies” to penicillin. If the risk of serious allergic reaction (anaphylaxis) to penicillin is deemed significant, traditionally, prophylaxis has been attempted with either erythromycin or clindamycin. Both of these cross the placenta (clindamycin much better than erythromycin), although they do so more slowly than penicillin. The larger problem with these antibiotics is that GBS resistance rates are as high as 35-40% for erythromycin and range between 15% and 30% for clindamycin. If a woman is suspected to be allergic to penicillin, and known to be a carrier, or at risk for GBS colonization, susceptibility testing should be requested at the time culture is performed for GBS.
The dilemma becomes apparent when a pregnant woman is allergic to penicillin and also has GBS that is resistant to these other antibiotics, particularly clindamycin. Vancomycin is highly active against GBS and has been suggested as an alternative under these circumstances, although effective dosage regimens are not yet clear. Dr. Joann Laiprasert recently reported at the meeting of the Infectious Diseases Society for Obstetrics and Gynecology that vancomycin, given to 13 healthy pregnant volunteers, achieved therapeutic levels in the fetuses, but not without maternal complications. An attempt was made to administer 1 gram of the drug intravenously over 60 minutes and 90 minutes. More than half of the women did not complete the full course of therapy because they developed a complication common to vancomycin recipients termed “Red Man’s Syndrome.” Symptoms include itching, rash, shortness of breath and hypotension. One woman required oxygen therapy, but no apparent fetal complications developed. More work will obviously have to be done here before vancomycin can be considered to be the ‘alternative of choice.’ By the way, did I mention what vancomycin COSTS$$$$$$$$
There are several other high risk situations in which prophylactic GBS therapy is also currently recommended including:
• Premature labor or rupture of membranes before 37 weeks
• Prolonged rupture of membranes (18 hr or longer) before delivery
• Fever in labor (100.4F or higher)
• History of GBS urinary tract infection during the pregnancy (4-fold risk)
• Previous baby affected by GBS disease (increases risk 10-fold!!!)
Some practitioners will also treat all women who present in labor and have not received prenatal care or who missed routine screening for GBS at 35-37 weeks, although the risk/benefit ratio of this approach is not necessarily proven. According to the CDC, women who are GBS positive, and not in one of the ‘high risk’ groups above, have about a 1 in 200 chance of having a baby who develops GBS disease if antibiotics are NOT given and only 1 in 4000 risk if they are given. Cesarean delivery is NOT indicated to prevent GBS transmission to the baby.