CHLORAMPHENICOL

Fetal Risk Summary

No reports linking the use of chloramphenicol with congenital defects have been located. The drug crosses the placenta at term producing cord serum concentrations 30%–106% of maternal levels (1,2).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 98 of whom had 1st trimester exposure to chloramphenicol (3, pp. 297–301). For use anytime in pregnancy, 348 exposures were recorded (3, p. 435). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations or to individual defects. A 1977 case report described a 14-day course of IV chloramphenicol, 2 g daily, given to a patient with typhoid fever in the 2nd trimester (4). A normal infant was delivered at term. Twenty-two patients, in various stages of gestation, were treated with chloramphenicol for acute pyelonephritis (5). No difficulties in the newborn could be associated with the antibiotic. In a controlled study, 110 patients received one to three antibiotics during the 1st trimester for a total of 589 weeks (6). Chloramphenicol was given for a total of 205 weeks. The incidence of birth defects was similar to that in controls.

Although apparently nontoxic to the fetus, chloramphenicol should be used with caution at term. Although specific details were not provided, one report claimed that cardiovascular collapse (gray syndrome) developed in babies delivered from mothers treated with chloramphenicol during the final stage of pregnancy (7). Additional reports of this severe adverse effect have not been located, although it is well-known that newborns exposed directly to high doses of chloramphenicol may develop the gray syndrome (8, 9). Because of this risk, some authors consider the drug to be contraindicated during pregnancy (10).

Breast Feeding Summary

Chloramphenicol is excreted into human breast milk. Two milk samples, separated by 24 hours in the same patient, were reported as 16 and 25 µmg/mL, representing milk:plasma ratios of 0.51 and 0.61, respectively (11). Both active drug and inactive metabolite were measured. No effect on the infant was mentioned. No infant toxicity was mentioned in a 1964 report that found peak levels occurring in milk 1–3 hours after a single 1-g oral dose (12). In a similar study, continuous excretion of chloramphenicol into breast milk was established after the 1st day of therapy (13). Minimum and maximum milk concentrations were determined for five patients receiving 250 mg orally every 6 hours (0.54 and 2.84 µmg/mL) and for five patients receiving 500 mg orally every 6 hours (1.75 and 6.10 µmg/mL). No infant data were given.

The safety of maternal chloramphenicol consumption and breast feeding is unknown. The American Academy of Pediatrics classifies the antibiotic as an agent whose effect on the nursing infant is unknown but may be of concern because of the potential for idiosyncratic bone marrow suppression (14). Another publication recommended that chloramphenicol not be used in the lactating patient (15). Milk levels of this antibiotic are too low to precipitate the gray syndrome, but a theoretical risk does exist for bone marrow depression. Two other potential problems of lesser concern involve the modification of bowel flora and possible interference with the interpretation of culture results if a fever workup is required. Several adverse effects were reported in 50 breast-fed infants whose mothers were being treated with chloramphenicol including refusal of the breast, falling asleep during feeding, intestinal gas, and heavy vomiting after feeding (16).

References

1. Scott WC, Warner RF. Placental transfer of chloramphenicol (Chloromycetin). JAMA 1950;142:1331–2.
2. Ross S, Burke RG, Sites J, Rice EC, Washington JA. Placental transmission of chloramphenicol (Chloromycetin). JAMA 1950;142:1361.
3. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
4. Schiffman P, Samet CM, Fox L, Neimand KM, Rosenberg ST. Typhoid fever in pregnancy-with probable typhoid hepatitis. NY State J Med 1977;77:1778–9.
5. Cunningham FG, Morris GB, Mickal A. Acute pyelonephritis of pregnancy: a clinical review. Obstet Gynecol 1973;42:112–7.
6. Ravid R, Roaff R. On the possible teratogenicity of antibiotic drugs administered during pregnancy. In Klingberg MA, Abramovici H, Chemke J, eds. Drugs and Fetal Development. New York, NY:Plenum Press, 1972:505–10.
7. Oberheuser F. Praktische Erfahrungen mit Medikamenten in der Schwangerschaft. Therapiewoche 1971;31:2200. As reported in Manten A. Antibiotic drugs. In Dukes MNG, ed. Meyler's Side Effects of Drugs. Volume VIII. New York, NY:American Elsevier, 1975:604.
8. Sutherland JM. Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol. J Dis Child 1959;97:761–7.
9. Weiss CV, Glazko AJ, Weston JK. Chloramphenicol in the newborn infant. A physiologic explanation of its toxicity when given in excessive doses. N Engl J Med 1960;262:787–94.
10. Schwarz RH, Crombleholme WR. Antibiotics in pregnancy. South Med J 1979;72:1315–8.
11. Smadel JE, Woodward TE, Ley HL Jr, Lewthwaite R. Chloramphenicol (Chloromycetin) in the treatment of Tsutsugamushi disease (scrub typhus). J Clin Invest 1949;28:1196–215.
12. Prochazka J, Havelka J, Hejzlar M. Excretion of chloramphenicol by human milk. Cas Lek Cesk 1964;103:378–80.
13. Prochazka J, Hejzlar M, Popov V, Viktorinova D, Prochazka J. Excretion of chloramphenicol in human milk. Chemotherapy 1968;13:204–11.
14. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.
15. Anonymous. Update: drugs in breast milk. Med Lett Drugs Ther 1979;21:21–4.
16. Havelka J, Frankova A. Contribution to the question of side effects of chloramphenicol therapy in newborns. Cesk Pediatr 1972;21:31–3.