Antibiotic
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Vancomycin is an antibiotic that is used for gram-positive bacteria when either the organisms are resistant to less toxic anti-infectives (e.g., penicillins and cephalosporins) or the patient is sensitive to these agents. No cases of congenital defects attributable to vancomycin have been located. The manufacturer has received reports on the use of vancomycin in pregnancy without adverse fetal effects (A.F. Crumley, personal communication, Eli Lilly, 1983).
FETAL RISK SUMMARY
Reproduction studies in rats and rabbits at doses up to 1 and 1.1 times the maximum recommended human dose based on BSA (MRHD), respectively, have revealed no teratogenic effects. No effects on fetal weight or development were seen with the same doses in rats or slightly lower doses in rabbits (0.74 times the MRHD) (1).
The pharmacokinetics of vancomycin in a woman at 26.5 weeks’ gestation was described in a 1991 reference (2). Accumulation of the antibiotic, administered as 1 g IV every 12 hours (15 mg/kg/dose), was demonstrated in amniotic fluid (1.02 mcg/mL on day 1; 9.2 mcg/mL on day 13). At delivery at 28 weeks’ gestation, cord blood levels were 3.65 mcg/mL (6 hours after the mother’s maximum serum concentration), 76% of the mother’s serum level. The newborn’s serum level, 3.25 hours after birth, was 2.45 mcg/mL, indicating a half-life in the infant of 10 hours (2).
In a 2007 report, 13 nonlaboring, noninfected women at term, scheduled for cesarean section, were given a single 1-g IV dose of vancomycin (3). The full 1-g dose could be given to only six women, because four of five women given a 60-minute infusion and three of eight given a 90-minute infusion experienced a reaction to the antibiotic (“red man syndrome”: pruritus, shortness of breath, flushing, headache, and one case of hypotension). All seven infants had normal Apgar scores and blood gasses. Scheduling complications also prevented giving the vancomycin at the planned intervals before delivery. The actual time intervals from the end of the infusion to maternal sample were 26–509 minutes, and there was a strong correlation between cord and maternal concentrations. Regardless of the interval, all 13 cord serum samples contained low amounts of vancomycin (3–9.4 mcg/mL), but these amounts were considered to be above the minimal inhibitory concentration for group B streptococcus (3).
Vancomycin was used for subacute bacterial endocarditis prophylaxis in a penicillin-allergic woman at term with mitral valve prolapse (4). One hour before vaginal delivery, a 1-g IV dose was given during 3 minutes (recommended infusion time is 60 minutes [1,5]). Immediately after the dose, maternal blood pressure fell from 130/74 to 80/40 mmHg and then recovered in 3 minutes. Fetal bradycardia, 90 beats/minute, persisted for 4 minutes. No adverse effects of the hypotension-induced fetal distress were observed in the newborn. The Apgar scores were 9 and 10 at 1 and 5 minutes, respectively (4).
A 1989 report examined the effects of multiple-dose vancomycin on newborn hearing and renal function (6). Ten pregnant, drug-dependent women were treated with IV vancomycin (1 g every 12 hours for at least 1 week) for suspected or documented infections caused by methicillin-resistant Staphylococcus aureus. Of the 10 women, 4 also received concomitant gentamicin. Two control groups, neither of which received antibiotics, were formed: 10 infants from nondrug-dependent mothers (group 2), and 10 infants from drug-dependent mothers (group 3). Auditory brainstem response testing was conducted on the infants at birth and at 3 months of age, and blood urea nitrogen and serum creatinine were measured at birth. The placental transfer of vancomycin was measured in two patients with cord blood levels of 16.7 and 13.2 mcg/mL, 6 and 2.5 hours after infusion, respectively. At birth, abnormal auditory brainstem responses were measured in a total of six infants: two infants from the study group (neither exposed to gentamicin), three from control group 2, and one from control group 3. The hearing defect in all six infants was an absent wave V at 40 dB (the average behavioral threshold of adult listeners) in one or both ears. Repeat testing at 3 months in five infants was normal, indicating that the initial tests were falsely positive. In the sixth infant (in the study group), the tests at 3 months again showed no response in either ear at 40 dB. This infant’s mother had received a 2-g vancomycin dose after initial dosing had produced low serum levels (<20 mcg/mL) of the antibiotic. The peak serum level obtained following the double dose was 65.7 mcg/mL, a potentially toxic level if it was maintained. Following this, the mother was treated with the same regimen as the other women. On further examination, however, reduced compliance was discovered in both ears and the loss of hearing was diagnosed as a conduction defect, rather than sensorineural. Tests at 12 months, following improved compliance in both ears, were normal. Renal function studies in all 30 infants were also normal, although this latter conclusion has been challenged (7) and defended (8).
BREASTFEEDING SUMMARY
Vancomycin is excreted into breast milk. In one woman treated with IV vancomycin (1 g every 12 hours for at least 1 week), a milk level 4 hours after a dose was 12.7 mcg/mL (6). This value was nearly identical to the serum trough concentration measured at 12 hours in the mother during pregnancy. The effect on the nursing infant of vancomycin in milk is unknown. Vancomycin is poorly absorbed from the normal, intact gastrointestinal tract, and thus, systemic absorption would not be expected (5). However, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant (e.g., allergic response or sensitization), and interference with the interpretation of culture results if a fever workup is required.
References
1.Product information. Vancocin. Eli Lilly, 2000.
2.Bourget P, Fernandez H, Delouis C, Ribou F. Transplacental passage of vancomycin during the second trimester of pregnancy. Obstet Gynecol 1991;78:908–11.
3.Laiprasert J, Klein K, Mueller BA, Pearlman MD. Transplacental passage of vancomycin in noninfected term pregnant women. Obstet Gynecol 2007;109:1105–10.
4.Hill LM. Fetal distress secondary to vancomycin-induced maternal hypotension. Am J Obstet Gynecol 1985;153:74–5.
5.American Hospital Formulary Service. Drug Information 1997. Bethesda, MD: American Society of Health-System Pharmacists, 1997:403–8.
6.Reyes MP, Ostrea EM Jr, Cabinian AE, Schmitt C, Rintelmann W. Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant? Am J Obstet Gynecol 1989;161:977–81.
7.Gouyon JB, Petion AM. Toxicity of vancomycin during pregnancy. Am J Obstet Gynecol 1990;163:1375–6.
8.Reyes MP, Ostrea EM Jr. Toxicity of vancomycin during pregnancy. Reply. Am J Obstet Gynecol 1990;163:1376.