Rational application of antimicrobial drugs in pregnancy 1, penicillin Commonly used penicillin antibiotics include penicillin, ampicillin, amoxicillin, penicillin V, benzoxacillin, methicillin, cloxacillin, piperacillin, melphalan and alloxacillin. Penicillin antibiotics are all listed in Class B of the FDA classification and are safer for use in pregnancy. Given that the renal clearance of the drug increases with the glomerular filtration rate during pregnancy, pregnant women tend to have lower blood concentrations, and an appropriate increase in dosage may be considered. Yan Wei, Department of Gynecology, Fujian Provincial People’s Hospital To date, the most research has been done on penicillin, which has been used in clinical practice since the 1940s. The results of retrospective studies of the relevant populations have shown that the use of penicillin in the first three months of pregnancy has not been found to have an adverse effect on the embryo or the fetus. The use of penicillin in pregnancy with syphilis is effective in treating the mother and protecting the fetus. In the drug application monitoring study, no increase in the rate of fetal malformation caused by ampicillin, amoxicillin, penicillin V, benzoxycillin, etc. Ampicillin, amoxicillin and methicillin have low protein binding rate, easy to pass through the placenta and in the amniotic fluid to reach the maternal plasma drug concentration of 0.5-1 times; 90 minutes after the maternal injection of ampicillin, its blood concentration is equal to that of the fetus because of the immature renal function of the fetus, the The half-life of the drug is longer, 200-300 minutes later, the blood concentration in the fetus is 7 times greater than that in the mother. Ampicillin is used in obstetrics for premature rupture of membranes and prevention of intrauterine infections. Cloxacillin use has been reported to cause malformations in newborns born to pregnant women, but the correlation with the drug is uncertain and may be related in some way to illnesses suffered by their mothers during pregnancy. Piperacillin is not easy to pass through the placenta, it and meloxicillin, alloxacillin and other listed time is still short, there is no sufficient information to explain its safety in pregnancy, generally not recommended. 2, cephalosporins, in addition to pull the oxygen cephalosporin is included in the FDA’s class C, most of the cephalosporin belongs to the class B, the use of safer in pregnancy, but cefoperazone, cefmetazole, as well as pull the oxygen cephalosporin in the structure of the methyl thiotetrazolium side chain, which can reduce the prothrombinogen, and testosterone toxicity in animal experiments, it should be used with caution. Cephalosporins generally can pass through the placenta, but the concentration in the fetus is low, only a few tenths to one-third of the maternal concentration, with the exception of cefadroxil, which is used by pregnant women whose fetuses have blood concentrations up to twice that of the maternal concentration. As with penicillins, because the renal clearance of these drugs increases with glomerular filtration during pregnancy, pregnant women tend to have lower blood concentrations and may be considered for appropriate dose increases. Commonly used first-generation cephalosporins are cefadroxil, cefazolin, cefadroxil, and cefradine. Cefadroxil crosses the placenta and is used orally in obstetrics for the treatment of urinary tract infections with no teratogenic or other adverse effects on the fetus. Cardiovascular malformations and cleft lip and palate have occurred more frequently in fetuses of women who applied the drug in the first trimester of pregnancy, but this may be related to illnesses and coadministration of the drug by the mother during pregnancy. Cefazolin passes through the placenta into the fetal circulation and amniotic fluid, and some studies have reported that 1 hour after intravenous administration of 1 g in women in late pregnancy, the concentration of the drug in fetal umbilical blood is about one-third of that in the mother. Cephradine can rapidly pass through the placenta, intravenous administration in mid and late pregnancy, in the administration of about 50 up to the peak concentration of the drug in the umbilical cord blood and has a therapeutic concentration. Commonly used second-generation cephalosporins include cefuroxime, cefmetazole, and cefaclor. The first two drugs can rapidly pass through the placenta and reach therapeutic concentrations in fetal circulation and amniotic fluid when used in pregnancy. Commonly used third-generation cephalosporins are cefotaxime, cefazodime, ceftriaxone, ceftazidime, cefoperazone, cefixime, and cefbutene. The development of cephalosporins has been very rapid, and there are fewer data regarding them in drug application monitoring studies. The use of cefadroxil in pregnancy has not been found to increase the rate of fetal malformations; the use of cephradine, cefaclor and ceftriaxone pregnant women with higher rates of neonatal malformations, but the correlation with the drug is still uncertain, may be related to the diseases suffered by pregnant women and the combination of drugs and so on: other cephalosporins on the safety of the fetus is the lack of information on the study, no special circumstances should not be preferred to use. 3, β-lactamase inhibitors Imipenem, amitrazine, etc. belong to the FDA classification of class B, the lack of research data on the safety of the fetus, no special circumstances should not be preferred to use. Clavulanic acid, sulbactam, tazobactam and other β-lactamase inhibitors also belong to the FDA classification of class B, these drugs are rarely used alone, and more with other antibiotics to form a combination of preparations in animal experiments have not been found to have a teratogenic effect on the fetus, on the safety of women in pregnancy is the lack of research data. 4, aminoglycosides Aminoglycosides are not teratogenic, the effect on the fetus is mainly on the eighth on the brain neurotoxicity and nephrotoxicity. In addition to gentamicin FDA classified as class C, the other belong to class D. Aminoglycosides can pass through the placenta, and fetal blood concentrations are lower than maternal; maternal blood concentrations may be lower than normal during pregnancy and should be monitored. Aminoglycosides impair both cochlear and vestibular function; neomycin, kanamycin, and amikacin primarily affect hearing; streptomycin and gentamicin primarily involve the vestibule; tobramycin impairs cochlear and vestibular function to approximately equal degrees; ethyl viomycin is the least ototoxic. The toxicity of aminoglycosides to the eighth cerebral nerve can be divided into two types from the mechanism, one is dose-dependent, the occurrence of toxicity is related to the dosage of the drug, the method of medication, the course of treatment, renal insufficiency is more prone to occur, it is presumed to be a sustained high concentration of the drug in the lymph fluid of the inner ear, damage to the inner ear Cortex apparatus internal and external hair cells, the initial lesions may be reversible, but the damage exceeds a certain degree becomes irreversible, permanent deafness; the other is irreversible, permanent deafness; and the other is a permanent deafness. The initial lesion may be reversible, but the damage will become irreversible and permanent deafness after a certain period of time; the other is genetic mutation type, the occurrence of toxicity has no obvious relationship with the blood concentration and the concentration of the drug in the lymphatic fluid of the inner ear, it mainly occurs in the patients with genetic mutation, the mutation has been identified in the seventh pair of chromosomes, and the type of mutation is related to the ethnicity of the human race, and is mainly inherited from mothers, and these patients are abnormally sensitive to the ototoxicity of the aminoglycosides. The main site of impairment of renal function by aminoglycosides is the renal proximal tubule, but not the glomerulus. Nephrotoxicity in the order of kanamycin, cisomicin, gentamicin, amikacin, tobramycin, streptomycin decreasing. 5.Tetracyclines are classified as class D by FDA and are contraindicated in pregnancy. The effects of tetracycline on mother and child are manifold. Animal experiments show that early pregnancy with tetracycline embryotoxic effect on the fetus whether finger deformities or congenital cataracts and other teratogenic effects are still controversial, but pregnancy in the middle and late fetal bone and dental development time, tetracycline into the fetal body and calcium complex formation of complexes deposited in the bone and teeth, and chelated with calcium, the formation of a tetracycline-calcium orthophosphate complex, the fetus and the young child’s bone development is inhibited! The risk of this effect is greatest from the middle third of pregnancy; the use of tetracycline during the middle sixth of pregnancy can also cause enamel hypoplasia, brown pigmentation, yellow staining of the teeth of the fetus and young children, the degree of discoloration is related to the total amount of the drug used, and can be aggravated by repeated use of the drug; tetracycline can cause hepatic damage, and also has a toxic effect on the liver of the pregnant woman and fetus, and pregnant women who suffer from pyelonephritis or renal insufficiency are especially Tetracycline can cause liver damage and toxic effects on the liver of pregnant women and fetuses, and pregnant women with pyelonephritis or renal insufficiency, especially those with pyelonephritis or renal insufficiency, are prone to liver toxicity. The use of doxycycline, oxytetracycline, minocycline, memantine, etc., has been shown to have a high rate of neonatal malformations in mothers who have used these drugs during pregnancy, and should not be used during pregnancy. Doxycycline, oxytetracycline caused by tooth discoloration than other tetracycline drugs to light. 6, chloramphenicol Chloramphenicol is an amidol FDA classification for class C, chloramphenicol can pass through the placenta, late pregnancy application of this product, umbilical cord blood drug concentration of the mother’s 30-106%, has not been found to have a teratogenic effect, but chloramphenicol inhibit bone marrow hematopoietic function, resulting in neonatal gray baby syndrome or fetal death, so in the must be used, should be carried out to monitor the blood drug concentration. 7, macrolides FDA classification for class C, erythromycin as a representative drug. It is generally believed that erythromycin does not cause malformations, and no adverse effects on offspring have been found, but the drug rarely passes through the placenta and cannot play a therapeutic role in the fetus; erythromycin is used for the treatment of mycoplasma infections in pregnancy, which can reduce miscarriages and decrease the number of low birth-weight babies, and the data from drug use monitoring studies have shown that so far, no use of erythromycin has led to an increase in the incidence of malformations of infants at birth, but erythromycin esterification of odorless erythromycin is very toxic, and should be prohibited for use in pregnancy. However, the erythromycin esterified odorless erythromycin has a high degree of hepatotoxicity and should be contraindicated in pregnancy. The safety of erythromycins such as azithromycin, roxithromycin, clarithromycin, and medithromycin in pregnancy is not well documented. Spiramycin is widely used in Europe, no adverse effects on the fetus, toxoplasmosis infection in pregnant women preferred spiramycin or acetylspiramycin treatment. 8, sulfonamides FDA classified sulfadiazine as class B, not found to have a teratogenic effect, but it competes with bilirubin for protein-binding sites, which can lead to neonatal jaundice, bilirubin encephalopathy and hyperbilirubinemia, the late stages of pregnancy, especially during labor and delivery should not be used this product. Sulfamethoxazole (Synthroid) FDA classifies it as Category C. Animal studies have reported teratogenicity in rats, no similar effects in rabbits, but it can increase mortality in pregnant rabbits, and there is insufficient information in humans. Methotrexate FDA classifies it as class C, interferes with folic acid metabolism, and has teratogenic effects in animals. Methotrexate and sulfamethoxazole form compound sulfamethoxazole (cotrimoxazole), both of which can pass through the placenta, and the concentration in fetal blood is close to the level of maternal blood concentration, and a study of 2,296 pregnant women who had used cotrimoxazole during the first 3 months of pregnancy showed that there were 126 newborns with A study of 2296 pregnant women who had used cotrimoxazole in the first trimester of pregnancy showed that 126 newborns had large birth defects, suggesting that there may be a correlation between cotrimoxazole and a high rate of neonatal malformations, and that it should not be used during pregnancy. 9, quinolones commonly used quinolones are norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, enrofloxacin, lomefloxacin and sparfloxacin, the FDA classification for the C class, animal experiments did not find that quinolones have a teratogenic effect, there is no embryotoxicity, but there is a weak mutagenic effect in large doses; quinolones can cause cartilage in the load-bearing joints in the tissue of the immature animal lesion, which is most sensitive to the dogs. Sensitive. In animal experiments, ciprofloxacin was found in high concentrations in osteoarticular cartilage, and cartilage tissue destruction was seen in light and electron microscopy, and had not recovered after % weeks of drug withdrawal. There is little information on the use of quinolones in human pregnancy, with only 2 of 132 neonates born to pregnant women treated with ciprofloxacin reported to be born with defects, which is less than the expected 2-3% risk; ciprofloxacin passes slowly through the placenta, and the concentration of the drug in the amniotic fluid exceeds the maternal blood concentration by a factor of 10 after 12 hours of dosing. It has also been documented that 35 pregnant women who had been treated with norfloxacin or ciprofloxacin for urinary tract infections in the first 3 months of pregnancy were born with healthy infants, with no malformations or joint abnormalities found. In view of the above results of animal experiments, it is suggested that caution must be exercised when using quinolone antibacterial drugs on pregnant women. 10.Others Vancomycin FDA classified as class C, can pass through the placenta, mid-pregnancy application of vancomycin to treat chorioamnionitis can reach therapeutic concentration, no teratogenic effect was found, but it can cause fetal ototoxicity, the use of which should be used with special caution. Furaltoxin has no adverse effects on the fetus, because it can pass through the placenta, theoretically, it may cause hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient fetuses, but it has not been reported clinically. The teratogenic effect of furazolidone on the fetus has not been reported, glucose-6-phosphate dehydrogenase deficiency may produce hemolytic anemia after the application of this product, should be used with caution in late pregnancy. Clindamycin is commonly used in the treatment of drug-resistant anaerobic infections during labor and delivery, especially intra-amniotic fluid and post-delivery infections, and can pass through the placenta and reach therapeutic concentrations in fetal tissues. Summary The above classification of antimicrobial drugs according to its safety in pregnancy made a brief introduction, clinical work must be borne in mind, pregnancy is a very special physiological period, the use of antimicrobial drugs, in addition to the effectiveness of the drug should be considered on the pathogenic bacteria, the safety of the drug is very important, should be maximized to avoid the use of drugs on the fetus to cause adverse effects, reduce birth defects. From this point of view, erythromycin can be used, but other drugs in the macrolide group should be cautious, odorless erythromycin has great hepatotoxicity, and pregnant women should be prohibited from using it.