Search

In 27 women with fetuses affected by beta-thalassemia major, termination of gestation between 19 and 21 weeks was induced by amniocentesis and intrauterine instillation of prostaglandin F2 alpha. Pharmacokinetics in maternal blood and amniotic fluid were studied after at least three doses of one of the following antibiotics and before prostaglandin F2 alpha infusion: (1) cefoxitin, 2 gm, intravenously, 1/2-hour infusion, three times per day; (2) moxalactam, 2 gm, intravenously, 1/2-hour infusion, three times per day; and (3) ceftazidime, 1 gm, intramuscularly, three times per day. Successful amniotic fluid levels effective against various pathogens implicated in maternal-fetal infections appeared at least 3 hours beyond administration of the drug and ranged between 2.3 and 6.7 micrograms/ml, 1.56 and 15 micrograms/ml, and 1.5 and 5 micrograms/ml for cefoxitin, moxalactam, and ceftazidime, respectively. Beyond the third-hour after infusion a percentage ratio of amniotic fluid to simultaneous maternal serum level of almost greater than or equal to 50 was constantly observed for all studied antibiotics. Cefoxitin serum levels were about the same as those in nonpregnant women, while moxalactam and ceftazidime serum levels were 50% lower than the expected level in normal individuals.

Despite the increasing popularity of antibiotic prophylaxis to reduce febrile morbidity in patients who undergo cesarean delivery, little is known of the pharmacokinetics of antibiotics in the patient at term gestation. This study was designed to elucidate the pharmacokinetics of cefoxitin when administered intravenously or by uterine and peritoneal lavage at cesarean section. Significant differences were found in the values for total body clearance area under the serum concentration-time curve (AUC), and K21 of cefoxitin administered intravenously to pregnant patients at term gestation compared to values for these parameters observed in nonpregnant patients. The concentration of cefoxitin in decidual tissue after uterine and peritoneal lavage with the antibiotic was 92.5 +/- 10.1 micrograms/gm (mean +/- SEM), whereas the concentration of cefoxitin in decidual tissue after intravenous administration of the antibiotic was 36.9 +/- 10.5 micrograms/gm (mean +/- SEM). This difference is statistically significant (p less than 0.05). We conclude that the pharmacokinetics of cefoxitin are altered in the pregnant patient as evidenced by the increased rapidity of clearance of the antibiotic (total body clearance for cefoxitin in pregnant patients, 20.41 L/hr). Moreover, uterine and peritoneal lavage results in significant tissue concentrations of antibiotic, which is of potential importance since the decidua is a presumed site of initiation of bacterial infection after cesarean section.

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.