Hepatotoxicity of Erythromycin Estolate During Pregnancy

Abstract

Women in the second half of pregnancy, who were infected with genital mycoplasmas and who gave written informed consent, were randomly assigned to receive capsules of identical appearance containing erythromycin estolate, clindamycin hydrochloride, or a placebo for 6 weeks. Levels of serum glutamic oxalacetic transaminase (SGOT) were determined before and during treatment by a fluorometric method. All pretreatment levels of SGOT were normal (<41 units). Participants who received erythromycin estolate had significantly more abnormally elevated levels of SGOT (16/161, 9.9%) than did those who received clindamycin (4/168, 2.4%, P < 0.01) or those who received placebo (3/165, 1.8%, P < 0.01). Elevated levels of SGOT ranged from 44 to 130 U. Serum bilirubin levels were normal. Gamma-glutamyl transpeptidase activity was abnormal in six of six participants who had abnormal levels of SGOT while receiving erythromycin estolate. There were few associated symptoms, and all levels of SGOT returned to normal after cessation of treatment. The treatment of pregnant women with erythromycin estolate may be inadvisable.Erythromycin, a macrolide antibiotic produced by the actinomycete Streptomyces erythreus, has been used extensively in clinical medicine since its introdluction in 1952. Erythromycin base and its salts are not consistently absorbed from the gastrointestinal tract, presumably because they are destroyed by gastric acid. The only preparation of erythromycin that is well absorbed when given orally is the lauryl sulfate salt of the propionyl ester (propionyl erythromycin lauryl sulfate; erythromycin estolate [5]). The estolate is also the only form of erythromycin that has been associated with any reported hepatotoxicity. As reviewed by Braun (1), there have been reports of individuals who have developed hepatic toxicity in association with the administration of erythromycin estolate (8). Even when the propensity of erythromycin to produce hepatic toxicity has been considered to be established, it has been generally considered that this is an unusual idiosyncratic reaction (1, 5). The present report describes a group of pregnant women, over 9% of whom developed subclinical hepatotoxicity while receiving erythromycin estolate. Investigators in this laboratory have associated the genital mycoplasmas Mycoplasma hominis and Ureaplasma urealyticum (T-mycoplasmas) with birth weight. In one study (9), these organisms were found to be more prevalent among low-birth-weight infants than among infants of normal birth weight. In another study (3), women who were colonized with these organisms early in pregnancy gave birth to infants that weighed significantly less than infants whose mothers were not colonized. Earlier studies from this laboratory had found that non-bacteriuric pregnant women who were treated with a broad-spectrum antimicrobial agent gave birth to significantly fewer lowbirth-weight infants than did women who received a placebo (4; H. A. Elder, R. Smith, and E. H. Kass, Program Abstr. Intersci. Conf. Antimicrob. A...

Erythromycin‐induced genotoxicity and hepatotoxicity in mice pups treated during prenatal and postnatal period

“…Hepatotoxicity due to drugs and specially antibiotics are predominantly reported . The hepatotoxicity‐related oxidative stress induced by EMC in normal as well as pregnancy was prereported . In some hepatoprotective models, EMC has been used, for the induction of hepatotoxicity .…”

S2k – Guideline on the Therapy of Acne

“…Poor passage through placenta but accumulation in the fetal liver [462]. Erythromycin estolate is not recommended since increased aspartate aminotransferase values have developed with use longer than 3 weeks [484]. Erythromycin (and also ampicillin) temporarily reduces the urine estradiol level during the time they are administered (small case series, 9 days of use).…”

Dermatologic Surgery and the Pregnant Patient

“…Penicillin V-potassium, amoxicillin, and cephalosporins are thought to be safe, and metronidazole and the macrolides are felt to have minimal risk. 63 Aminoglycosides, such as gentamicin, may induce ototoxicity in the fetus when given late in pregnancy. 61,62 C. difficile colitis has also been reported with a variety of other antibiotics, however, it is more frequently reported with the use of clindamycin.…”