Antimicrobial therapy during pregnancy

Abstract

Like anybody else, pregnant women are susceptible to infections. The correct treatment of these women, however, must consider along with pathogens, the infection site and antibiotic pharmacokinetics, the fetus and possible side effects to the child. When prescribing over this special condition, the physician must remember that the prescription will affect two people and the drug must treat the mother without affect the fetus. Beta-lactams having a long history of use without significant deleterious effects on the fetuses still are the safest choice during pregnancy. However, considering the constant increase of multi-resistant microorganisms, the physician has been forced to use some kind of different antimicrobial agent. Usually, data regarding safety during pregnancy are very limited on the "newer agents", which causes serious doubts during their prescription. In addition, many studies regarding the safety use of antibiotics during pregnancy are inconclusive or demand more evidences. The present study is a wide revision regarding the use of antibiotics during pregnancy, considering their pharmacokinetics and the clinical experience in recent years. © Copyright Moreira Jr. Editora.Como quaisquer pessoas, gestantes estão sujeitas às infecções. O correto tratamento dessas mulheres deve considerar, além da sensibilidade dos patógenos, o local da infecção, a farmacocinética do antibiótico, os possíveis efeitos colaterais no feto e no neonato. Ao prescrever nessa condição especial, o médico deve lembrar-se que estará prescrevendo para dois organismos distintos e o fármaco deve tratar a mãe sem afetar o feto. Os beta-lactâmicos têm uma longa história de uso sem efeitos significativos no fetos e ainda são a escolha mais segura durante a gestação, embora o constante aumento no número de microrganismos multirresistentes tenha forçado os médicos a prescreverem diferentes antimicrobianos. Normalmente os dados a respeito da segurança de fármacos durante a gestação são muito limitados, causando dúvidas no momento da prescrição. Some-se a isso o fato de que muitos estudos sobre a segurança de antibióticos durante a gestação são inconclusivos ou demandam maiores evidências. O presente trabalho é uma ampla revisão a respeito do uso de antibióticos durante a gestação, sua farmacocinética e experiência clínica recente643111119Mantovani, A., Calamandrei, G., Delayed developmental effects following prenatal exposure to drugs (2001) Curr Pharm Des, 7, pp. 859-880Mengue, S.S., Schenkel, E.P., Duncan, B.B., Schmidt, M., Drug use by pregnant women in six Brazilian cities (2001) Rev Saude Publica, 35, pp. 415-420Gomes, K.R., Moron, A.F., Silva, R., Siqueira, A.A., Prevalence of use of medicines during pregnancy and its relationship to maternal factors (1999) Rev Saude Publica, 33, pp. 246-254Rao, J.M., Arulappu, R., Drug use in pregnancy. How to avoid problems (1981) Drugs, 22, pp. 409-414Christensen, B., Which antibiotics are appropriate for treating bacteriuria in pregnancy? (2000) J Antimicrob Chemother, 46, pp. 29-34Dashe, J.S., Gilstrap, L.C., Antibiotic use in pregnancy (1997) Obstet Gynecol Clin North Am, 24, pp. 617-629Sa Del Fiol, F., Rocha, D., Mattos Filho, T., Groppo, F.C., Evaluation in an animai model and in vitro of the combination clavulanic acid and cephalosporins against beta-lactamase producing and nonproducing Staphylococcus aureus strains (2000) Braz J Infect Dis, 4, pp. 36-42Loebstein, R., Lalkin, A., Koren, G., Pharmacokinetic changes during pregnancy and their clinical relevance (1997) Clin Pharmacokinet, 33, pp. 328-343Weller, T.M.A., Rees, E.N., Antibacterial use in pregnancy (2000) Drug Saf, 22, pp. 335-338Philipson, A., Stiernstedt, G., Ehrnebo, M., Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women (1987) Clin Pharmacokinet, 12, pp. 136-144Niebyl, J.R., Antibiotics and other anti-infective agents in pregnancy and lactation (2003) Am J Perinatol, 20, pp. 405-414Loebstein, R., Koren, G., Clinical relevance of therapeutic drug monitoring during pregnancy (2002) Ther Drug Monit, 24, pp. 15-22Boobis, A.R., Lewis, P., Drugs in pregnancy. Altered pharmacokinetics (1982) Br J Hosp Med, 28, pp. 566-573Briggs, G.G., Freeman, R.K., Yaffe, S.J., (2002) Drugs in pregnancy and lactation, pp. 284-312. , 6th ed. Baltimore: Williams & WilkinsCzeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., A population-based case-control teratologic study of ampicillin treatment during pregnancy (2001) Am J Obstet Gynecol, 185, pp. 140-147Blanchard, M., Oppliger, R., Bucher, U., Positive direct Coombs' test in acute leukemias and other hemoblastoses: Relation to clavulanic acid-containing antibiotics? (1989) Schweiz Med Wochenschr, 119, pp. 39-45Williams, M.E., Thomas, D., Harman, C.P., Mintz, P.D., Donowitz, G.R., Positive direct antiglobulin tests due to clavulanic acid (1985) Antimicrob Agents Chemother, 27, pp. 125-127Czeizel, A.E., Rockenbauer, M., Olsen, J., Use of antibiotics during pregnancy (1998) Eur J Obstet Gynecol Reprod Biol, 81, pp. 1-8Fonseca, M.R.C.C., Fonseca, E., Bergsten-Mendes, G., Prevalence of drug use during pregnancy: A pharmacopepidemiological approach (2002) Rev Saude Publica, 36, pp. 205-212Czeizel, A.E., Rockenbauer, M., Olsen, J., Sorensen, H.T., Oral Phenoxymethylpenicillin treatment during pregnancy. Results of a population-based Hungarian case- control study (2000) Arch Gynecol Obstet, 263, pp. 178-181Dencker, B.B., Larsen, H., Jensen, E.S., Schonheyder, H.C., Nielsen, G.L., Sorensen, H.T., Birth outcome of 1886 pregnancies after exposure to Phenoxymethylpenicillin in utero (2002) Clin Microbiol Infect, 8, pp. 196-201Larsen, H., Nielsen, G.L., Sorensen, H.T., Moller, M., Olsen, J., Schonheyder, H.C., A follow-up study of birth outcome in users of pivampicillin during pregnancy (2000) Acta Obstet Gynecol Scand, 79, pp. 379-383Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Teratogenic evaluation of oxacillin (1999) Scand J Infect Dis, 31, pp. 311-312Aselton, P., Jick, H., Milunsky, A., Hunter, J.R., Stergachis, A., First-trimester drug use and congenital disorders (1985) Obstet Gynecol, 65, pp. 451-455Jepsen, P., Skriver, M.V., Floyd, A., Lipworth, L., Schonheyder, H.C., Sorensen, H.T., A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark (2003) Br J Clin Pharmacol, 55, pp. 216-221Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: A population-based case-control teratologic study (2001) Eur J Obstet Gynecol Reprod Biol, 97, pp. 188-192Shepherd, G.M., Hypersensitivity reactions to drugs: Evaluation and management (2003) Mt Sinai J Med, 70, pp. 113-125Heikkila, A., Erkkola, R., Review of beta-lactam antibiotics in pregnancy. The need for adjustment of dosage schedules (1994) Clin Pharmacokinet, 27, pp. 49-62Einarson, A., Shuhaiber, S., Koren, G., Effects of antibacterials on the unborn child: What is known and how should this influence prescribing (2001) Paediatr Drugs, 3, pp. 803-816Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: A population-based, case-control study (2001) Am J Obstet Gynecol, 184, pp. 1289-1296Heikkila, A., Renkonen, O.V., Erkkola, R., Pharmacokinetics and transplacental passage of imipenem during pregnancy (1992) Antimicrob Agents Chemother, 36, pp. 2652-2655Bristol-Myers Squibb Company: Azactam®: Food and Drug Administration. 2004http://www.fda.gov/ cder/foi/label/2002/50580slr033lbl.pdf, searched May 2004Matsuda, S., Suzuki, M., Oh, K., Ishikawa, M., Soma, A., Takada, H., Shimizu, T., ChimuraT, Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in the perinatal period. A study of imipenem/cilastatin sodium in the perinatal co-research group (1988) Jpn J Antibiot, 41, pp. 1731-1741Greenwood, D., Inhibitors of bacterial protein synthesis (1997) Antimicrobial chemotherapy, pp. 32-48. , Greenwood D ed, 3rd ed, Oxford University PressReyes, M.P., Ostrea Jr, E.M., Cabinian, A.E., Schmitt, C., Rintelmann, W., Vancomycin during pregnancy: Does it cause hearing loss or nephrotoxicity in the infant? (1989) Am J Obstet Gynecol, 161, pp. 977-981Mensa, J., García-Vázquez, E., Vila, J., Macrólidos, cetólidos y estreptograminas (2003) Enferm lnfecc Microbiolo Cin, 21, pp. 200-208Hedstrom, S., Martens, M.G., Antibiotics in pregnancy (1993) Clin Obstet Gynecol, 36, pp. 886-892Larsen, B., Glover, D.D., Serum erythromycin levels in pregnancy (1998) Clin Ther, 20, pp. 971-977Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., A population-based case-control teratologic study of oral erythromycin treatment during pregnancy (1999) Reprod Toxicol, 13, pp. 531-536Lewis, J.H., Drug-induced liver disease (2000) Med Clin North Am, 84, pp. 1275-1311Honein, M.A., Paulozzi, L.J., Himelright, I.M., Lee, B., Cragan, J.D., Patterson, L., Correa, A., Erickson, J.D., Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromcyin: A case review and cohort study (1999) Lancet, 354, pp. 2101-2105Louik, C., Werler, M.M., Mitchell, A.A., Erythromycin use during pregnancy in relation to pyloric stenosis (2002) Am J Obstet Gynecol, 186, pp. 288-290Sorensen, H.T., Skriver, M.V., Pedersen, L., Larsen, H., Ebbesen, F., Schonheyder, H.C., Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides (2003) Scand J Infect Dis, 35, pp. 104-106Einarson, A., Phillips, E., Mawji, F., D'Alimonte, D., Schick, B., Addis, A., Mastroiacova, P., Koren, G., A prospective controlled multicentre study of clarithromycin in pregnancy (1998) Am J Perinatal, 15, pp. 523-525Food and Drug Administration Revision - Biaxin® Granules - Abbott Laboratories2000 http:// www.fda.gov/cder/foi/label/2000/50662S29lbl.pdf, searched May 2004Schonwald, S., Kuzman, I., Oreskovic, K., Burek, V., Skerk, V., Car, V., Bozinovic, D., Radosevic, S., Azithromycin: Single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome - a randomized study (1999) Infection, 27, pp. 198-202Bush, M.R., Rosa, C., Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy (1994) Obstet Gynecol, 84, pp. 61-63Pfizer Laboratories: Zithromax®. Food and Drug Administration2003 http://www.fda.gov/cder/foi/label/ 2004/50670slr021,50693slr008,50730slr011_ zithromax_lbl.pdf, searched may, 2004Douthwaite, S., Hansen, L.H., Mauvais, P., Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain Il of 23S rRNA (2000) Mol Microbiol, 36, pp. 183-193Jamjian, C., Biedenbach, D.J., Jones, R.N., In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004 (1997) Antimicrob Agents Chemother, 41, pp. 454-459Aventis Pharmaceutical Inc. KETEK™ - Telithromycin. Food and Drug Administration2004. http:// www.fda.gov/cder/foi/label/2004/21144_ketekj bl.pdf, searched may, 2004Philipson, A., Sabath, L.D., Charles, D., Transplacental passage of erythromycin and clindamycin (1973) N Engl J Med, 288, pp. 1219-1221Weinstein, A.J., Gibbs, R.S., Gallagher, M., Placental transfer of clindamycin and gentamicin in term pregnancy (1976) Am J Obstet Gynecol, 124, pp. 688-691Mickal, A., Panzer, J.D., The safety of lincomycin in pregnancy (1975) Am J Obstet Gynecol, 121, pp. 1071-1074Czeizel, A.E., Rockenbauer, M., Olsen, J., Sorensen, H.T., A teratological study of aminoglycoside antibiotic treatment during pregnancy (2000) Scand J Infect Dis, 32, pp. 309-313Chan, K.W., WL, N., Gentamicin nephropathy in a neonate (1985) Pathology, 17, pp. 514-515Conway, N., Birt, B.D., Streptomycin in pregnancy: Effect on the foetal ear (1965) Br Med J, 31, pp. 260-263Donald, P.R., Sellars, S.L., Streptomycin ototoxicity in the unborn child (1981) S Afr Med J, 22, pp. 316-318Marynowski, A., Sianozecka, E., Comparison of the incidence of congenital malformations in neonates from healthy mothers and from patients treated because of tuberculosis (1972) Ginekol Pol, 43, pp. 713-715Murphy, J.F., Drugs and pregnancy (1984) Ir Med J, 77, pp. 52-56Chambers HS Antimicrobial Agents: Protein Synthesis Inhibitors and Miscellaneous Antibacterial Agents. In: Hardman JG, Gilman AG, Limbird LE (ed.) Goodman & Gilman's The Pharmacological Basis of Therapeutics, 1996, McGraw-Hill, 1239-1272Czeizel, A.E., Rockenbauer, M., A population-based case-control teratologic study of oral Oxytetracycline treatment during pregnancy (2000) Eur J Obstet Gynecol Reprod Biol, 88, pp. 27-33Hautekeete, M.L., Hepatotoxicity of antibiotics (1995) Acta Gastroenterol Belg, 58, pp. 290-296Onur MA, Vural I, Kas HS, Hincal AA, Coskun T, Kanra G, Turner A. Decrease in the placental transfer of chloramphenicol when administered in albumin microspheres into rats. J Microencapsul. 199310: 367-374Johnson, T.N., The development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children (2003) Toxicology, 92, pp. 37-48Knight, M., Adverse drug reactions in neonates (1994) J Clin Pharmacol, 34, pp. 128-135Sorensen, H.T., Larsen, H., Jensen, E.S., Thulstrup, A.M., Schonheyder, H.C., Nielsen, G.L., Czeizel, A., Safety of metronidazole during pregnancy: A cohort study of risk of congenital abnormalities, preterm delivery and low birth weight in 124 women (1999) J Antimicrob Chemother, 44, pp. 854-856Rodin, P., Hass, G., Metronidazole and pregnancy (1966) Br J Vener Dis, 42, pp. 210-212Piper, J.M., Mitchel, E.F., Ray, W.A., Prenatal use of metronidazole and birth defects: No association (1993) Obstet Gynecol, 82, pp. 348-352Beard, C.M., Noller, K.L., O'Fallon, W.M., Kurland, L.T., Dahlin, D.C., Cancer after exposure to metronidazole (1988) Mayo Clin Proc, 63, pp. 147-153Saravanos, K., Duff, P., The quinolone antibiotics (1992) Obstet Gynecol Clin North Am, 19, pp. 529-537Loebstein, R., Addis, A., Ho, E., Andreou, R., Sage, S., Donnenfeld, A.E., Schick, B., Koren, G., Pregnancy outcome following gestational exposure to fluoroquinolones: A multicenter prospective controlled study (1998) Antimicrob Agents Chemother, 42, pp. 1336-1339Hooton, T.M., Stamm, W.E., Diagnosis and treatment of uncomplicated urinary tract infection (1997) Infect Dis Clin North Am, 11, pp. 551-581Grady R Safety profile of quinolone antibiotics in the pediatric population. Pediatr Infect Dis J. 200322: 1128-1132Yabe, K., Yoshida, K., Yamamoto, N., Nishida, S., Ohshima, C., Sekiguchi, M., Yamada, K., Furuhama, K., Diagnosis of quinolone-induced arthropathy in juvenile dogs by use of magnetic resonance (MR) imaging (1997) J Vet Med Sci, 59, pp. 597-599Nagai, A., Miyazaki, M., Morita, T., Furubo, S., Kizawa, K., Fukumoto, H., Sanzen, T., Kawamura, Y., Comparative articular toxicity of garenoxacin, a novel quinolone antimicrobial agent, in juvenile beagle dogs (2002) J Toxicol Sci, 27, pp. 219-228Berkovitch, M., Pastuszak, A., Gazarian, M., Lewis, M., Koren, G., Safety of the new quinolones in pregnancy (1994) Obstet Gynecol, 84, pp. 535-538Danisovicova, A., Brezina, M., Belan, S., Kayserova, H., Kaiserova, E., Hruskovic, I., Orosova, K., Matheova, E., Magnetic resonance imaging in children receiving quinolones: No evidence of quinolone-induced arthropathy. A multicenter survey (1994) Chemotherapy, 40, pp. 209-214Reid, D.W., Caille, G., Kaufmann, N.R., Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination (1975) Can Med Assoc J, 14, pp. 67-72Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., The teratogenic risk of trimethoprim-sulfonamides: A population based case-control study (2001) Reprod Toxicol, 15, pp. 637-646Ahlfors, C.E., Unbound bilirubin associated with kernicterus: A historical approach (2000) J Pediatr, 137, pp. 540-544Perkins, R.P., Hydrops fetalis and stillbirth in a male glucose-6-phosphate dehydrogenase-deficient fetus possibly due to maternal ingestion of sulfisoxazolea case report (1971) Am J Obstet Gynecol, 111, pp. 379-381Hernandez-Diaz, S., Werler, M.M., Walker, A.M., Mitchell, A.A., Folic acid antagonists during pregnancy and the risk of birth defects (2000) N Engl J Med, 343 (30), pp. 1608-1614Like anybody else, pregnant women are susceptible to infections. The correct treatment of these women, however, must consider along with pathogens, the infection site and antibiotic pharmacokinetics, the fetus and possible side effects to the child. When prescribing over this special condition, the physician must remember that the prescription will affect two people and the drug must treat the mother without affect the fetus. Beta-lactams having a long history of use without significant deleterious effects on the fetuses still are the safest choice during pregnancy. However, considering the constant increase of multi-resistant microorganisms, the physician has been forced to use some kind of different antimicrobial agent. Usually, data regarding safety during pregnancy are very limited on the "newer agents", which causes serious doubts during their prescription. In addition, many studies regarding the safety use of antibiotics during pregnancy are inconclusive or demand more evidences. The present study is a wide revision regarding the use of antibiotics during pregnancy, considering their pharmacokinetics and the clinical experience in recent year

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