妊娠及哺乳期应用抗生素的研究现状

Research Progress of Antibiotic Use During Pregnancy and Lactation

抗生素是妊娠及哺乳期最常用的药物之一。妊娠及哺乳期抗生素的药动学与药效学可能发生改变,从而影响疗效。此外,抗生素对发育中的胎儿或新生儿可能存在致畸或毒性作用。对妊娠及哺乳期常用的11种广谱抗生素的文献资料进行综述。11种抗生素均能穿过胎盘进入胎儿体内,均能分泌至乳汁。阿莫西林、庆大霉素、青霉素G、青霉素V钾、环丙沙星、左氧氟沙星的血药浓度妊娠期较未妊娠妇女偏低,表明若需达到未妊娠妇女的血药浓度,必须缩短用药间隔和(或)加大给药剂量。妊娠期克林霉素药动学无改变。妊娠期应用氯霉素、庆大霉素或万古霉素时,建议检测血药峰-谷浓度。根据"致畸因子信息服务分类系统",上述11种抗生素可被分为:无致畸危险(如青霉素G及青霉素V钾)、不大可能致畸(如阿莫西林、氯霉素、环丙沙星、多西环素、左氧氟沙星及利福平)、不确定是否致畸(如克林霉素、庆大霉素及万古霉素)3类。根据美国FDA制定的"妊娠期药物危险分级"标准,阿莫西林、克林霉素、青霉素G、青霉素V钾及万古霉素均属于B级;氯霉素、环丙沙星、庆大霉素、左氧氟沙星及利福平皆为C级;多西环素为D级。

Antibiotics are among the most commonly prescribed medications for pregnant and lactating women. In addition to their pharmacokinetic and pharmacodynamic changes that may occur during pregnancy and lactation, and that can alter the effectiveness of drugs, there are some possible teratogenic and toxic effects on the fetus and newborn. This article reviews the available data for a group of 11 broad-spectrum antibiotics frequently prescribed during pregnancy and laction. All 11 antibiotics can penetrate placenta and enter the fetal compartment, as well as are excreted from breast milk. For amoxicillin, gentamicin, penicillin G, penicillin VK, ciprofloxacin and levofloxacin, a lower circulating drug concentrations were measured in pregnant women than nonpregnant, suggesting that a shorter dosing interval or increased maternal dose or both may be necessary to obtain similar circulating drug concentrations as for women in the nonpregnant state. In use of chloramphenicol, gentamicin or vancomycin during the pregnancy, the drug monitoring of serum peak and trough is recommended to assess circulating drug levels. The changes of clindamycin pharmacokinetic parameters were not observed during pregnancy. Based on the Teratogen Information Service classification system, above-mentioned antibiotics can be classified into ＂no teratogenic risk＂ （penicillin G and penicillin VK）, ＂unlikely to have teratogenic effects＂ （amoxicillin, chloramphenicol, ciprofloxacin, doxycycline, levofloxacin and rifampin） and ＂undetermined if it has teratogenic resk＂ （clindamycin, gentamicin and vancomycin）. According to Food and Drug Administration Pregnancy Category classifications, amoxicillin, clindamycin, penicillin G, penicillin VK, and vancomycin are grade B; chloramphenicol, ciprofloxacin, gentamicin, levofloxacin and rifampin are grade C; and doxycycline is grade D.