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Am J Perinatol 2003; 20(8): 405-414
DOI: 10.1055/s-2003-45391
REVIEW ARTICLE

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Antibiotics and Other Anti-infective Agents in Pregnancy and Lactation

Jennifer R. Niebyl
  • Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
Further Information

Publication History

Publication Date:
02 January 2004 (online)

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ABSTRACT

Serum levels of many drugs are lower in pregnancy compared with the nonpregnant state. Their renal clearance is higher and the maternal intravascular volume is expanded. Most antibiotics are safe for use in pregnancy and lactation. Tetracyclines cause fetal tooth discoloration and inhibition of bone growth if used in the second and third trimesters. Aminoglycosides carry a small risk of fetal ototoxicity. Quinolones may cause arthropathies in children, and so are currently not recommended for use in pregnancy. Most drugs are secreted into breast milk in very small amounts, not enough to have any therapeutic effect. The only antibiotics which may be of concern in nursing infants are sulfonamides and quinolones, and possibly metronidazole.

KEYWORDS

Antibiotics - pregnancy - lactation

REFERENCES

  • 1 Heinonen P O, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy.  Littleton, MA: Publishing Sciences Group 1977: 296-313
    Google Scholar
  • 2 Aselton P, Jick H, Milunsky A, Hunter J R, Stergachis A. First-trimester drug use and congenital disorders.  Obstet Gynecol . 1985;  65 451-455
    PubMedGoogle Scholar
  • 3 Heikkila A M, Erkkola R U. The need for adjustment of dosage regimen of penicillin V during pregnancy.  Obstet Gynecol . 1993;  81 919-921
    PubMedGoogle Scholar
  • 4 Macaulay M A, Berg S A, Charles D. Placental transfer of dicloxacillin at term.  Am J Obstet Gynecol . 1968;  102 1162-1168
    PubMedGoogle Scholar
  • 5 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 1078
    Google Scholar
  • 6 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 284
    Google Scholar
  • 7 Kafetzis D, Siafas C, Georgakopoulos P, Papadatos C. Passage of cephalosporins and amoxicillin into the breast milk.  Acta Paediatr Scand . 1981;  70 285-288
    PubMedGoogle Scholar
  • 8 Depp R, Kind A, Kirby W, Johnson W. Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid.  Am J Obstet Gynecol . 1970;  107 1054-1057
    PubMedGoogle Scholar
  • 9 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 222
    Google Scholar
  • 10 Czeizel A E, Rockenbauer M, Sorensen H T. et al . Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: a population-based, case-control study.  Am J Obstet Gynecol . 2001;  184 1289-1296
    CrossrefPubMedGoogle Scholar
  • 11 Nathorst-Boos J, Philipson A, Hedman A, Arvisson A. Renal elimination of ceftazidime during pregnancy.  Am J Obstet Gynecol . 1995;  172 163-166
    CrossrefPubMedGoogle Scholar
  • 12 Sheng K T, Huang N N, Promadhattavedi V. Serum concentrations of cephalothin in infants and children and placental transmission of the antibiotic.  Antimicrob Agents Chemother . 1964;  10 200-206
    PubMedGoogle Scholar
  • 13 Harris R C, Lucey J F, MacLean J R. Kernicterus in premature infants associated with low concentration of bilirubin in the plasma.  Pediatrics . 1958;  21 875-884
    PubMedGoogle Scholar
  • 14 Ylikorkala O, Sjostedt E, Jarvinen P A, Tikkanen R, Raines T. Trimethoprim-sulfonamide combination administered orally and intravaginally in the first trimester of pregnancy: its absorption into serum and transfer to amniotic fluid.  Acta Obstet Gynecol Scand . 1973;  52 229-234
    PubMedGoogle Scholar
  • 15 Colley D P, Kay J, Gibson G T. A study of the use in pregnancy of co-trimoxazole and sulfamethizole.  Aust J Pharm . 1982;  63 570-575
    PubMedGoogle Scholar
  • 16 Bailey R R. Single-dose antibacterial treatment for bacteriuria in pregnancy.  Drugs . 1984;  27 183-186
    PubMedGoogle Scholar
  • 17 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 1393
    Google Scholar
  • 18 Czeizel A. A case-control analysis of the teratogenic effects of co-trimoxazole.  Reprod Toxicol . 1990;  4 305-313
    CrossrefPubMedGoogle Scholar
  • 19 Hernandez-Diaz S, Werler M M, Walker A M. et al . Folic acid antagonists during pregnancy and the risk of birth defects.  N Engl J Med . 2000;  343 1608-1614
    CrossrefPubMedGoogle Scholar
  • 20 Jarnerot G, Into-Malmberg M B, Esbjorner E. Placental transfer of sulphasalazine and sulphapyridine and some of its metabolites.  Scand J Gastroenterol . 1981;  16 693-697
    PubMedGoogle Scholar
  • 21 Mogadam M. Sulfasalazine, IBD, and pregnancy: reply.  Gastroenterology . 1981;  81 194
    PubMedGoogle Scholar
  • 22 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 1293
    Google Scholar
  • 23 Committee on Drugs. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk.  Pediatrics   2001;  108 776-789
    PubMedGoogle Scholar
  • 24 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 1000
    Google Scholar
  • 25 Hosbach R H, Foster R B. Absence of nitrofurantoin from human milk.  JAMA . 1967;  202 1057
    CrossrefPubMedGoogle Scholar
  • 26 Varsano I, Fischl J, Shochet S B. The excretion of orally ingested nitrofurantoin in human milk.  J Pediatr . 1973;  82 886-887
    PubMedGoogle Scholar
  • 27 Kline A H, Blattner R J, Lunin M. Transplacental effect of tetracycline on teeth.  JAMA . 1964;  118 178-180
    PubMedGoogle Scholar
  • 28 Cohlan S Q, Bevelander G, Tiamsic T. Growth inhibition of prematures receiving tetracycline.  Am J Dis Child . 1963;  105 453-461
    PubMedGoogle Scholar
  • 29 Czeizel A E, Rockenbauer M. Teratogenic study of doxycycline.  Obstet Gynecol . 1997;  89 524-528
    CrossrefPubMedGoogle Scholar
  • 30 Robinson G C, Cambon K G. Hearing loss in infants of tuberculous mothers treated with streptomycin during pregnancy.  N Engl J Med . 1964;  271 949-951
    PubMedGoogle Scholar
  • 31 Nishimura H, Tanimura T. Clinical aspects of the teratogenicity of drugs.  Amsterdam: Excerpta Medica 1976: 13
    Google Scholar
  • 32 L'Hommedieu C S, Nicholas D, Armes D A, Jones P, Nelson T, Pickering L K. Potentiation of magnesium sulfate-induced neuromuscular weakness by gentamicin, tobramycin, and amikacin.  J Pediatr . 1983;  102 629-631
    PubMedGoogle Scholar
  • 33 Czeizel A E, Rockenbauer M, Olsen J. et al . A teratological study of aminoglycoside antibiotic treatment during pregnancy.  Scand J Infect Dis . 2000;  32 309-313
    PubMedGoogle Scholar
  • 34 Marynowski A, Sianozecka E. Comparison of the incidence of congenital malformations in neonates from healthy mothers and from patients treated because of tuberculosis.  Ginekol Pol . 1972;  43 713-715
    PubMedGoogle Scholar
  • 35 Weinstein A J, Gibbs R S, Gallagher M. Placental transfer of clindamycin and gentamicin in term pregnancy.  Am J Obstet Gynecol . 1976;  124 688-691
    PubMedGoogle Scholar
  • 36 Zaske D E, Cipolle R J, Strate R G, Malo J W, Koszalka M F. Rapid gentamicin elimination in obstetric patients.  Obstet Gynecol . 1980;  56 559-564
    PubMedGoogle Scholar
  • 37 Yoshioka H, Monma T, Matsuda S. Placental transfer of gentamicin.  J Pediatr . 1972;  80 121-123
    PubMedGoogle Scholar
  • 38 Nicolau D P, Freeman C D, Belliveau P P, Nightingale C H, Ross J W, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2184 adult patients.  Antimicrob Agents Chemother . 1995;  39 650-655
    PubMedGoogle Scholar
  • 39 Munckhof W J, Grayson M L, Turnidge J D. A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses.  J Antimicrob Chemother . 1996;  37 645-663
    CrossrefPubMedGoogle Scholar
  • 40 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 treatment of puerperal infection.  Am J Obstet Gynecol . 1997;  177 786-792
    PubMedGoogle Scholar
  • 41 Celiloglu M, Celiker S, Guven H. et al . Gentamicin excretion and uptake from breast milk by nursing infants.  Obstet Gynecol . 1994;  84 263-265
    PubMedGoogle Scholar
  • 42 Briggs G G, Freeman R K, Yaffe S J. Drugs in Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 502
    Google Scholar
  • 43 Louik C, Werler M M, Mitchell A A. Erythromycin use during pregnancy in relation to pyloric stenosis.  Am J Obstet Gynecol . 2002;  186 288-290
    CrossrefPubMedGoogle Scholar
  • 44 Einarson A, Phillips E, Mawji F. et al . A prospective controlled multicentre study of clarithromycin in pregnancy.  Am J Perinatol . 1998;  15 523-525
    PubMedGoogle Scholar
  • 45 Philipson A, Sabath L D, Charles D. Transplacental passage of erythromycin and clindamycin.  N Engl J Med . 1973;  288 1219-1221
    PubMedGoogle Scholar
  • 46 South M A, Short D H, Knox J M. Failure of erythromycin estolate therapy in in utero syphilis.  JAMA . 1964;  190 70-71
    PubMedGoogle Scholar
  • 47 Briggs G G, Freeman R K, Yaffe S J. Drugs and Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 286-287
    Google Scholar
  • 48 Berkovitch M, Pastuszak A, Gazarian M, Lewis M, Koren G. Safety of the new quinolones in pregnancy.  Obstet Gynecol . 1994;  84 535-538
    PubMedGoogle Scholar
  • 49 Pastuszak A, Andreou R, Schick B. et al . New postmarketing surveillance data supports a lack of association between quinolone use in pregnancy and fetal and neonatal complications.  Reprod Toxicol . 1995;  9 584
    CrossrefPubMedGoogle Scholar
  • 50 Briggs G G, Freeman R K, Yaffe S J. Drugs and Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 271
    Google Scholar
  • 51 Beard C M, Noller K L, O'Fallon W M, Kurland L T, Dockerty M T. Lack of evidence for cancer due to use of metronidazole.  N Engl J Med . 1979;  301 519-522
    PubMedGoogle Scholar
  • 52 Finegold S M. Metronidazole.  Ann Intern Med . 1980;  93 585-587
    PubMedGoogle Scholar
  • 53 Piper J M, Mitchel E F, Ray W A. Prenatal use of metronidazole and birth defects: no association.  Obstet Gynecol . 1993;  82 348-352
    PubMedGoogle Scholar
  • 54 Burtin P, Taddio A, Ariburnu O, Einarson T R, Koren G. Safety of metronidazole in pregnancy: a meta-analysis.  Am J Obstet Gynecol . 1995;  172 525-529
    CrossrefPubMedGoogle Scholar
  • 55 Centers for Disease Control. Pregnancy outcomes following systemic prenatal acyclovir exposure: June 1, 1984-June 30, 1993.  MMWR Morb Mortal Wkly Rep . 1993;  42 806-809
    PubMedGoogle Scholar
  • 56 Scott L L, Sanchez P J, Jackson G L, Zeray F, Wendel Jr D G. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes.  Obstet Gynecol . 1996;  87 69-73
    CrossrefPubMedGoogle Scholar
  • 57 Stray-Pedersen B. Acyclovir in late pregnancy to prevent neonatal herpes simplex.  Lancet . 1990;  336 756
    PubMedGoogle Scholar
  • 58 Watts H D, Brown Z A, Money D. et al . A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery.  Am J Obstet Gynecol . 2003;  188 836-843
    CrossrefPubMedGoogle Scholar
  • 59 Andrews E B, Yankaskas B C, Cordero J F, Schoeffler K, Hampp S. Acyclovir in pregnancy registry: six years' experience.  Obstet Gynecol . 1992;  79 7-13
    PubMedGoogle Scholar
  • 60 Sheffield J S, Fish D N, Hollier L M. Acyclovir concentrations in human breast milk after valacyclovir administration.  Am J Obstet Gynecol . 2002;  186 100-102
    CrossrefPubMedGoogle Scholar
  • 61 Culnane M, Fowler M G, Lee S S. et al . Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women.  JAMA . 1999;  281 151-157
    CrossrefPubMedGoogle Scholar
  • 62 McGowan J P, Crane M, Wiznia A A. et al . Combination antiretroviral therapy in human immunodeficiency virus-infected pregnant women.  Obstet Gynecol . 1999;  94 641-646
    CrossrefPubMedGoogle Scholar
  • 63 Watts D H. Management of human immunodeficiency virus infection in pregnancy.  N Engl J Med . 2002;  346 1879-1891
    PubMedGoogle Scholar
  • 64 Dabis F, Msellati P, Meda N, for the DITRAME Study Group. et al . Six-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial.  Lancet . 1999;  353 786-792
    CrossrefPubMedGoogle Scholar
  • 65 Rosa F. Amantadine pregnancy experience [comment; letter].  Reprod Toxicol . 1994;  8 531
    CrossrefPubMedGoogle Scholar
  • 66 Centers for Disease Control. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices.  MMWR Morb Mort Wkly Rep . 2000;  49 1-38
    PubMedGoogle Scholar
  • 67 Briggs G G, Freeman R K, Yaffe S J. Drugs and Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 45
    Google Scholar
  • 68 Briggs G G, Freeman R K, Yaffe S J. Drugs and Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 731
    Google Scholar
  • 69 American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children.  Am J Respir Crit Care Med   1994;  149 1359-1374
    PubMedGoogle Scholar
  • 70 Boggess K A, Myers E R, Hamilton C D. Antepartum or postpartum isoniazid treatment of latent tuberculosis infection.  Obstet Gynecol . 2000;  96 757-762
    CrossrefPubMedGoogle Scholar
  • 71 Briggs G G, Freeman R K, Yaffe S J. Drugs and Pregnancy and Lactation 6th ed.  Baltimore: Williams & Wilkins; 2002: 732
    Google Scholar
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