ERYTHROMYCIN

Fetal Risk Summary

No reports linking the use of erythromycin with congenital defects have been located. The drug was not teratogenic in female rats fed erythromycin (up to 0.25% of the diet) before and during mating, and throughout gestation and weaning (1).

Erythromycin crosses the placenta but in concentrations too low to treat most pathogens (2,3 and 4). Fetal tissue levels increase after multiple doses (4). However, a case has been described in which erythromycin was used successfully to treat maternal syphilis but failed to treat the fetus adequately (5). During pregnancy, erythromycin serum concentrations vary greatly as compared to those in normal men and nonpregnant women, which might account for the low levels observed in the fetus (6).

The estolate salt of erythromycin has been observed to induce hepatotoxicity in pregnant patients (7). Approximately 10% of 161 women treated with the estolate form in the 2nd trimester had abnormally elevated levels of serum glutamic-oxaloacetic transaminase, which returned to normal after therapy was discontinued.

The use of erythromycin in the 1st trimester was reported in a mother who delivered an infant with left absence-of-tibia syndrome (8). The mother was also exposed to other drugs, which makes a relationship to the antibiotic unlikely.

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 79 of whom had 1st trimester exposure to erythromycin (9, pp. 297–313). For use anytime during pregnancy, 230 exposures were recorded (9, p. 435). No evidence was found to suggest a relationship to large categories of major and minor malformations or to individual defects. Erythromycin, like many other antibiotics, lowers urine estriol concentrations (see also Ampicillin for mechanism and significance) (10). The antibiotic has been used during the 3rd trimester to reduce maternal and infant colonization with group B b-hemolytic streptococcus (11,12). Erythromycin has also been used during pregnancy for the treatment of genital mycoplasmas (13, 14). A reduction in the rates of pregnancy loss and low-birth-weight infants was seen in patients with mycoplasma infection after treatment with erythromycin.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 6,972 newborns had been exposed to erythromycin during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 320 (4.6%) major birth defects were observed (297 expected). Specific data were available for six defect categories, including (observed/expected) 77/70 cardiovascular defects, 14/11 oral clefts, 1/3 spina bifida, 22/20 polydactyly, 14/12 limb reduction defects, and 11/17 hypospadias. These data do not support an association between the drug and congenital malformations.

Breast Feeding Summary

Erythromycin is excreted into breast milk (15). Following oral doses of 400 mg every 8 hours, milk levels ranged from 0.4 to 1.6 µg/mL. Oral doses of 2 g/day produced milk concentrations of 1.6–3.2 µg/mL. The milk:plasma ratio in both groups was 0.5. No reports of adverse effects in infants exposed to erythromycin in breast milk have been located. However, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant, and interference with the interpretation of culture results if a fever workup is required. The American Academy of Pediatrics considers the antibiotic to be compatible with breast feeding (16).

References

1. Product information. Ery-Tab. Abbott Laboratories, 2000.
2. Heilman FR, Herrell WE, Wellman WE, Geraci JE. Some laboratory and clinical observations on a new antibiotic, erythromycin (Ilotycin). Proc Staff Meet Mayo Clin 1952;27:285–304.
3. Kiefer L, Rubin A, McCoy JB, Foltz EL. The placental transfer of erythromycin. Am J Obstet Gynecol 1955;69:174–7.
4. Philipson A, Sabath LD, Charles D. Transplacental passage of erythromycin and clindamycin. N Engl J Med 1973;288:1219–20.
5. Fenton LJ, Light LJ. Congenital syphilis after maternal treatment with erythromycin. Obstet Gynecol 1976;47:492–4.
6. Philipson A, Sabath LD, Charles D. Erythromycin and clindamycin absorption and elimination in pregnant women. Clin Pharmacoal Ther 1976;19:68–77.
7. McCormack WM, George H, Donner A, Kodgis LF, Albert S, Lowe EW, Kass EH. Hepatotoxicity of erythromycin estolate during pregnancy. Antimicrob Agents Chemother 1977;12:630–5.
8. Jaffe P, Liberman MM, McFadyen I, Valman HB. Incidence of congenital limb-reduction deformities. Lancet 1975;1:526–7.
9. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
10. Gallagher JC, Ismail MA, Aladjem S. Reduced urinary estriol levels with erythromycin therapy. Obstet Gynecol 1980;56:381–2.
11. Merenstein GB, Todd WA, Brown G, Yost CC, Luzier T. Group B B-hemolytic streptococcus: randomized controlled treatment study at term. Obstet Gynecol 1980;55:315–8.
12. Easmon CSF, Hastings MJG, Deeley J, Bloxham B, Rivers RPA, Marwood R. The effect of intrapartum chemoprophylaxis on the vertical transmission of group B streptococci. Br J Obstet Gynaecol 1983;90:633–5.
13. Quinn PA, Shewchuk AB, Shuber J, Lie KI, Ryan E, Chipman ML, Nocilla DM. Efficacy of antibiotic therapy in preventing spontaneous pregnancy loss among couples colonized with genital mycoplasmas. Am J Obstet Gynecol 1983;145:239–44.
14. Kass EH, McCormack WM. Genital mycoplasma infection and perinatal morbidity. N Engl J Med 1984;311:258.
15. Knowles JA. Drugs in milk. Pediatr Currents 1972;21:28–32.
16. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.