Abstract
The use of antimicrobials in pregnancy is associated with a potential risk for deleterious effect on fetus and neonate. Pregnancy may be associated with changes in pharmacokinetics because of reduced renal blood flow and glomerular filtration, increased blood volume, changes in albumin concentrations. The above factors can lead to suboptimal dosing regimens. Antimicrobials may have the following effects: embryotoxic, teratogenic, fetotoxic. Initial safety information is obtained from analysis of chemical structure, in vitro and animal studies. The main data are collected in clinical and observational studies. The most widely used criteria for determination of possibility of drugs use in pregnancy are FDA recommendations. In Australia and Sweden more detailed classifications are in use. In general, the majority of antimicrobials are relatively safe for fetus. It could be explained by the absence of specific target in mammalian cells. In addition, antimicrobials are usually administered by relatively short courses compare to other drugs. At the same time the duration of exposure is one of the crucial factors in the development of teratogenic effect.
-
1.
Rao J.M., Arulappu R. Drug use in pregnancy. How to avoid problems. Drugs 1981; 22:409-14.
-
2.
De Vigan C., De Walle H.E., Cordier S. Therapeutic drug use during pregnancy: a comparison in four European countries. OECM Working Group. Occupational expo- sures and congenital anomalies. J Clin Epidemiol 1999; 52:977–82.
-
3.
Korzeniowski O.M. Antibacterial agents in pregnancy. Infect Dis Clin North Am 1995; 9:639-51.
-
4.
Chow A.W., Jewesson P.J. Pharmacokinetics and safety of antimicrobial agents during pregnancy. Rev Infect Dis 1985; 7:287-313.
-
5.
Philipson A. Pharmacokinetics of antibiotics in pregnan- cy and labour. Clin Pharmacokinet 1979; 4:297-309.
-
6.
Weller T.M.A., Rees E.N. Antibacterial use in Pregnancy. Drug Safety 2000; 22:335-8.
-
7.
Zhang Y., Zhang Q., Xu Z. Tissue and body fluid distrib- ution of antibacterial agents in pregnant and lactating women. Zhonghua Fu Chan Ke Za Zhi 1997; 32:288-92.
-
8.
Irl C., Hasford J. Assessing the Safety of Drugs in Pregnancy: The Role of Prospective Cohort Studies. Drug Safety 2000; 22:169-77.
-
9.
Mitchell A.A. Systematic Identification of drugs that cause birth defects - A New Opportunity. N Engl J Med 2003, 349:2556-9.
-
10.
Robbie M.O., Sweet R.L. Metronidazole use in obstetrics and gynecology: a review. Am J Obstet Gynecol 1983; 145:865-81.
-
11.
Kato T., Kitagawa S. Production of congenital abnormal- ities in the fetuses of rats and mice with various sulphonamides. Congenit Abnormal 1973; 13:7-15.
-
12.
Koren G., Pastuszak A., Ito S. Drugs in pregnancy. N Engl J Med 1998; 338:1128-37.
-
13.
Heinonen O.P., Sloane D., Shapiro S. Birth defects and drugs in pregnancy. Littleton (MA): Publishing Sciences Group, 1977. р.435.
-
14.
Hardy J.B. The Collaborative Perinatal Project: lessons and legacy. Ann Epidemiol 2003; 13:303-11.
-
15.
Kennedy D.L., Uhl K., Kweder S.L. Pregnancy Exposure Registries. Drug Safety 2004; 27:215-28.
-
16.
Kallen B.A.J., Olausson P.O. Maternal drug use in early pregnancy and infant cardiovascular defect. Repro- ductive Toxicology 2003; 17:255-61.
-
17.
Ferencz C., Correa-Villasenor A., Loffredo C.A., Wilson P.D. Genetics and environmental risk factors of major cardiovascular malformations: the Baltimore-Washing- ton Infant Study: 1981–1989. Perspect Ped Cardiol 5. New York: Futura Publishing Comp., Inc.; 1997.
-
18.
Witt A., Sommer E.M., Cichna M., Postlbauer K., Wid- halm A., Gregor H. Placental passage of clarithromycin surpasses other macrolide antibiotics. Am J Obstet Gynecol 2003; 188:816-9.
-
19.
Australian Drug Evaluation Committee. Medicines in Pregnancy. An Australian Categorization of Risk, 1992.
-
20.
PASS. Classification of medical products for use during pregnancy and lactation. The Swedish system. Stockholm: LINFO, Drug Information Ltd. 1993
-
21.
Астахова А.В., Лепахин В.К. Неблагоприятные побоч- ные реакции и контроль безопасности лекарств. Руко- водство по фармаконадзору. М: «Когито-Центр»; 2004.
-
22.
Addis A., SharabiS., BonatiM. Risk classifications sys- tems for drugs use during pregnancy. Drug Safety 2000; 23:245-53.
-
23.
Olsen J., Czeizel A., Sorensen H.T., Nielsen G.L., de Jong van den Berg L.T., Irgens L.M., et al. How do we best detect toxic effects of drugs taken during pregnancy? A EuroMap paper. Drug Saf 2002; 25:21-32.
-
24.
Polifka J.E., Friedman J.M. Clinical teratology: identify- ing teratogenic risks in humans. Clin Genet 1999; 56:409- 20.
-
25.
Hutter A., Parks J. The transmission of penicillin through the placenta: a preliminary report. Am J Obstet Gynecol 1945; 49:663-5.
-
26.
Heikkila A.M., Erkkola R.U. The need for adjustment of dosage regimen of penicillin V during pregnancy. Obstet Gynecol 1993; 81:919-21.
-
27.
Niebyl J.R. Antibiotics and Other Anti-infective Agents in Pregnancy and Lactation. Am J Perinatol 2003; 20:405-14.
-
28.
Jepsen P., Skriver M.V., Floyd A., Lipworth L., Schon- heyder H.C., Sorensen H.T. A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark. Br J Clin Pharmacol 2003; 55:216-21.
-
29.
Pedler S.J., Bint A.J. Comparative study of amoxi- cillin/clavulanic acid and cephalexin in the treatment of bacteruria during pregnancy. Antimicrob Agents Chemother 1985; 27:508-10
-
30.
Einarson A., Shuhaiber S., Koren G. Effects of antibacteri- als on the unborn child: what is known and how should this influence prescribing. Paediatr Drugs 2001; 3:803-16.
-
31.
Czeizel A.E., Rockenbauer M., Sorensen H.T. Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-con- trol study. Am J Obstet Gynecol 2001; 184:1289-96.
-
32.
Berkovitch M., Segal-Socher I., Greenberg R., Bulkowshtein M., Arnon J., Merlob P., Or-Noy A. First trimester exposure to cefuroxime: a prospective cohort study. Br J Clin Pharmacol 2000; 50:161-5.
-
33.
Heikkila A., Renkonen O.V., Erkkola R. Pharmacokinetics and transplacental passage of imipenem during pregnancy. Antimicrob Agents Chemother 1992; 36:2652-5.
-
34.
Czeizel A.E., Rockenbauer M., Sorensen H.T., Olsen J. A population-based case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol 1999; 13:531-6.
-
35.
Czeizel A.E., Rockenbauer M., Olsen J., Sorensen H. A case-control teratological study of spiramycin, rox- ithromycin, oleandomycin and josamycin. Acta Obstet Gynecol Scand 2000; 79:234-7
-
36.
McCormack W.M., George H., Donner A. Hepato- toxicity of erythromycin estolate during pregnancy. Antimicrob Agents Chemother 1977; 12:630-5.
-
37.
Einarson A., Phillips E., Mawji F., D’Alimonte D., Schick B., Addis A., et al. A prospective controlled multi- centre study of clarithromycin in pregnancy. Am J Perinatol 1998; 15:523-5.
-
38.
Bush M.R., Rosa L. Azithromycin and erythromycin in the treatment of cervical chlamydia infection during pregnancy. Obstet Gynecol 1994; 84:61-3.
-
39.
Adair C.D., Gunter M., Stovall T.G., McElroy G., Veille J.C., Ernest J.M. Chlamydia in pregnancy: a ran- domized trial of azithromycin and erythromycin. Obstet Gynecol 1998; 91:165-8.
-
40.
Desmonts G., Couvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. N Engl J Med 1974; 50:1110-6.
-
41.
Rosental M. How safe is that antimicrobial you are writ- ing for the female patient? Infectious disease news. September 2003.
-
42.
Marynowski A, Sianozecka E. Comparison of the inci- dence of congenital malformations in neonates from healthy mothers and from patients treated because of tuberculosis. Ginekol Pol 1972; 43:713-5.
-
43.
Leroux M. Existe-t-l une surdite congenitale acquise due a la streptomycine? Ann Otolaryngol 1950; 67:194-6.
-
44.
Robinson G.C., Cambon K.G. Hearing loss in infants of mothers treated with streptomycin during pregnancy. N Engl J Med 1964; 281:949-51.
-
45.
Conway N., Birt B.D. Streptomycin in pregnancy: effect on the fetal ear. BMJ 1965; II:260-3.
-
46.
Chan K.W., Ng W.L. Gentamycin nephropathy in the neonate. Pathology 1985; 17:514-5.
-
47.
Jones H.C. Intrauterine ototoxicity: a case report and review of the literature. J Natl Med Assoc 1973; 65:201-3.
-
48.
Bourget P., Fernandez H., Delouis C. Pharmacokinetics of tobramycin in pregnant women: safety and efficacy of a once-daily dose regimen. J Clin Pharm Ther 1991; 16:167-76.
-
49.
Mitra A.G., Whitten K., Laurent S.L., Anderson W.E. A randomized, prospective study comparing once-daily gentamicin versus thrice-daily gentamicin in the treat- ment of puerperal infection. Am J Obstet Gynecol 1997; 177:786-92.
-
50.
Stahlmann R., Merker H.J., Hinz N., Chahoud I., Webb J., Heger W., Neubert D. Ofloxacin in juvenile non- human primates and rats. Arthropathia and drug plasma concentrations. Arch Toxicol 1990; 64:193-204.
-
51.
Stahlmann R., Forster C., Shakibaei M., Vormann J., Gunther T., Merker H.J. Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical to quinolone-induced arthropathy. Antimicrob Agents Chemother 1995; 39:2013-8.
-
52.
Kato M., Onodera T. Morphological investigation of cav- ity formation in articular cartilage induced by ofloxacin in rats. Fundam Appl Toxicol 1988; 11:110-9.
-
53.
Gough A.W., Kasali O.B., Sigler R.E., Baragi V. Quinolone arthropathy-acute toxicity to immature artic- ular cartilage. Toxicol Pathol 1992; 20:436-49.
-
54.
Loebstein R., Addis A., Ho E., Andreou R., Sage S., Donnenfeld A.E., et al. Pregnancy outcome following gestational exposure to fluoroquinolones: a Multicenter prospective controlled study. Antimicrob Agent Chem 1998; 42:1336-9.
-
55.
Czeizel A.E., Rockenbauer M., Sorensen H. T., Olsen J. A teratological study of lincosamides. Scand J Infect Dis 2000; 32:579-580.
-
56.
Mickal A., Panzer J.D. The safety of lincomycin in preg- nancy. Am J Obstet Gynecol 1975; 121:1071-4.
-
57.
Forti G., Benincori C. Doxycycline in the teeth. Lancet 1969; I (7598):782
-
58.
Czeizel A.E., Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89:524-8.
-
59.
Czeizel A.E. Analysis of medical indications for induced abortions. Orvosi Hetilap 1983; 124:1297–302.
-
60.
Czeizel A.E., Rockenbauer M. A population-based case- control teratologic study of oral oxytetracycline treat- ment during pregnancy. Eur J Obstet Gynecol Reprod Biol 2000; 88:27-33.
-
61.
Warkany J. Antituberculous drugs. Teratology 1979; 20:133-8.
-
62.
Steen J.S.M., Stainton-Ellis D.M. Rifampin in pregnan- cy. Lancet 1977; II:604-5.
-
63.
Jentgens H. Antituberkulose chemotherapie und ssh- wanger-shaftsabburch. Prax Pneumol 1973; 27:479-88.
-
64.
Reid D.W.J., Caillie G., Kaufman N.R. Maternal and transplacental kinetics of trimethoprim and sulfamethox- azole, separately and in combination. Can Med Assoc J 1975; 1112:67-72S.
-
65.
Williams J.D., Condie A.P., Brumfitt W. The treatment of bacteriuria in pregnant women with sulfamethoxazole and trimethoprim. Postgrad Med J 1969; 45(Suppl.):71-6.
-
66.
Ochoa A.G. Trimethoprim and sulfamethoxazole in preg- nancy. JAMA 1971; 217:1244.
-
67.
Hernandez-Diaz S., Werler M.M., Walker A.M. Folic acid antagonists during pregnancy and the risks for birth defects. N Engl J Med 2000; 343:1608-14.
-
68.
Kantor H.I., Sutherland D.A., Leonard J.T. Effect on bilirubin metabolism in the newborn of sulfisoxazole administration to the mother. Obstet Gynecol 1961; 17:494-500.
-
69.
Perkins R.P. Fetal hydrops and stillbirth in a male glu- cose-6-phosphate dehydrogenase-deficient fetus possibly due to maternal ingestion of sulfisoxazole. Am J Obstet Gynecol 1971; 111:379-81.
-
70.
Briggs G.G., Freeman R.K., Yaffe S.J. Drugs in pregnan- cy and lactation. Baltimore: Williams and Wilkins, 1994. p.135-151.
-
71.
Hailey F.J., Fort H., Williams J.C. Foetal safety of nitrofurantoin macrocrystals therapy during pregnan- cy: a retrospective analysis. J Int Med Res 1983; 11:364-9.
-
72.
Lenke R.R., Van Dorsten J.P., Schifrin B.S. Pyelo- nephritis in pregnancy: a prospective randomised trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance. Am J Obstet Gynecol 1983; 146:953-7.
-
73.
Ben D.S., Einarson T., Nullman I., et al. The safety of nitrofurantoin during the first trimester: a meta-analysis. Clin Fundament Pharmacol 1995; 9:503-7.
-
74.
Powell R.D., deGowin R.L., Alving A.S. Nitrofurantoin- induced hemolysis. J Lab Clin Med 1963; 62:1002-3.
-
75.
Finegold S.M. Metronidazole. Ann Intern Med 1980; 93:585-7.
-
76.
Beard C.M., Noller K.L., O’Fallon W.M. Lack of evi- dence for cancer due to use of metronidazole. N Engl J Med 1979; 301:519-22.
-
77.
Cantu J.M., Garcia-Cruz D. Midline facial defect as a ter- atogenic effect of metronidazole. Birth Defects Orig Artic Ser 1982; 18:85-8.
-
78.
Piper J.M., Mitchel E.F., Ray W.A. Prenatal use of metronidazole and birth defects: no association. Obstet Gynecol 1993; 82:348-52.
-
79.
Czeizel A.E., Rockenbauer M. A population based case- control teratologic study of oral metronidazole. Br J Obstet Gynecol 1998; 105:322-7.
-
80.
Burtin P., Taddio A., Ariburnu O., et al. Safety of metron- idazole in pregnancy: a meta-analysis. Am J Obstet Gynecol 1995; 172:525-9.
-
81.
Caro-Paton T., Carvajal A., Martin Amas L.H. Is metron- idazole teratogenic: a meta-analysis. Br J Clin Pharmacol 1997; 44:179-82.
-
82.
MacCullock D. Vancomycin in pregnancy. NZ Med J 1981; 93:93-4.
-
83.
Smaill F. Intrapartum antibiotics for Group B streptoco- ccal colonisation (Cochrane Review). In: The Cochrane Library, issue 4. Oxford: Update Software, 2004.
-
84.
Conear E.M., Sperling R.S., Gelber R., et al. Reduction of maternal-infant transmission of human immunodeficien- cy virus with zidovudine treatment. N Engl J Med 1994; 331:1173-80.
-
85.
The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type a - a meta-analy- sis of 15 prospective cohort studies. N Engl J Med 1999; 340:977-87.
-
86.
Nolla-Salas J., Bosch J., Gasser I., et al. Perinatal Liste- riosis: a population-based multicenter study in Barce- lona, Spain (1990-1996). Am J Perinatol 1998; 15:461-7.
-
87.
A Alexander J.M., Sheffield J.S., Sanchez P.J. Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999; 93:5-8.
-
88.
Daffos F., Forestier F., Capella-Pavelovsky M. Prenatal management of 746 pregnancies at risk for congenital toxoplasmosis. N Engl J Med 1988; 318:271-5.
-
89.
Foulon W., Villena I., Stray-Pedersen B. Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children’s sequelae at age 1 year. Am J Obstet Gynecol 1999; 180:410-5.
-
90.
Enders G., Miller E., Cradock-Watson I., et al. Consequ- ences of Varicella exposure and Herpes-zoster in preg- nancy: a prospective study of 1739 cases. Lancet 1994; 343:1548-51.
-
91.
Koren G., Klinger G., Ohlsson A. Fetal pharmacotherapy. Drugs 2002; 62:757-73.
-
92.
Stray-Pedersen B. Treatment of toxoplasmosis in the pregnant mother and newborn child. Scand J Infect Dis 1992; 84:23-31.
-
93.
Australian Drug Evaluation Committee. Medicines in pregnancy. 3rd ed. Canberra: Australian Government Publishing Service; 1996.
-
94.
Bartlett J.G. Pocket book of infectious disease therapy. Baltimore: Lippincott Williams & Wilkins; 2000.