Use of Anti-Infective Agents During Lactation: Part 2—Aminoglycosides,Macrolides,Quinolones,Sulfonamides,Trimethoprim,Tetracyclines,Chloramphenicol,Clindamycin,and Metronidazole
Restricted accessResearch articleFirst published online February, 2001
Use of Anti-Infective Agents During Lactation: Part 2—Aminoglycosides,Macrolides,Quinolones,Sulfonamides,Trimethoprim,Tetracyclines,Chloramphenicol,Clindamycin,and Metronidazole
Because many antibiotics are excreted into breast milk, it can be difficult for a practitioner to choose an antibiotic for a lactating patient that will have minimal risks to her nursing infant. This article is the second of a three-part series discussing the use of anti-infective agents during lactation. The authors review general information regarding use and common side effects for several classes of antibiotics. They also summarize information, including documented milk concentrations, milk-to-plasma ratios, and other pharmacokinetic properties, in a table that can help practitioners choose antibiotics that may be considered safe to use in the lactating mother.
Chin KG, Mactal-Haaf C, McPherson CE III. Use of anti-infective agents during lactation: Part 1—beta-lactam antibiotics, vancomycin, quinupristin-dalfopristin, and linezolid. J Hum Lact. 2000;16:351-358.
2.
Edson RS, Terrell CL. Symposium on antimicrobial agents—Part VIII: the aminoglycosides. Mayo Clin Proc. 1999;74:519-528.
3.
Henry NK, Hoecker JL, Rhodes KH. Antimicrobial therapy for infants and children: guidelines for the inpatient and outpatient practice of pediatric infectious diseases. Mayo Clin Proc. 2000;75:86-97.
Salva P, Costa J, Andreu D, Notivol R, Martinez M. Tolerability and safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic solution: a randomized, comparative, controlled study in healthy volunteers. Methods Find Exp Clin Pharmacol. 1999;21:203-208.
6.
Trope GE, Lawrence JR, Hind VM, Everden A. Systemic absorption of topical and subconjunctival gentamicin. Br J Ophthalmol. 1979; 63:692-693.
7.
Alvarez-Elcoro S, Enzler MJ. Symposium on antimicrobial agents—part IX: the macrolides: erythromycin, clarithromycin and azithromycin. Mayo Clin Proc. 1999;74:613-634.
8.
Guay RP. Macrolide antibiotics in paediatric infectious diseases. Drugs. 1996;4:515-536.
9.
Eitches RW, Rachelefsky GS, Katz RM, Mendoza GR, Siegel SC. Methylprednisolone and troleandomycin in treatment of steroid-dependent asthmatic children. AJDC. 1985;139:264-268.
10.
Klein JO. History of macrolide use in pediatrics. Pediatr Infect Dis J. 1997;16:427-431.
11.
Nilsen OG. Pharmacokinetics of macrolides: Comparison of plasma, tissue and free concentrations with special reference to roxithromycin. Infection. 1995;(suppl)1:5-9.
12.
Amsden GW, Nafziger AN, Foulds G. Pharmacokinetics in serum and leukocyte exposures of oral azithromycin, 1,500 milligrams given over a 3-or 5-day period in healthy subjects. Antimicrob Agents Chemother. 1999;43:163-165.
13.
Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: a case review and cohort study. Lancet. 1999;354:2101-2105.
14.
San Filippo JA. Infantile hypertrophic pyloric stenosis related to ingestion of erythromycin estolate: a report of five cases. J Ped Surg. 1976; 11:177-179.
15.
Stang H. Pyloric stenosis associated with erythromycin ingested through breast milk. Minn Med. 1986;69:669-682.
16.
Rothman KF, Pochi PE. Use of oral and topical agents for acne in pregnancy. J Am Acad Dermatol. 1988;3:431-442.
17.
Moussa F, Alaswad B, Gardia J. Erythromycin eye ointment: effect on gastroinstestinal motility. Am J Gastroenterol. 2000;3:826-826.
Walker RC. The fluoroquinolones: symposium on antimicrobial agents—part XIII. Mayo Clin Proc. 1999;74:1030-1037.
20.
Bartlett JG, Breiman RF, Mandell LA, File TM. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 1998;26:818-838.
21.
Hale T. Medications and Mothers' Milk. 8th ed.Amarillo, Tex: Pharmasoft Medical Publishing; 1999.
22.
Schaad UB. Pediatric use of quinolones. Ped Infect Dis J. 1999;18:467-470.
23.
Ball P, Mandell L, Niki Y, Tillotson G. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Safety. 1999;21:407-421.
24.
Kucers A, Crowe SM, Grayson ML, Hoy JF: Sulfonamides. In Kucers A, et al., eds. The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, and Antiviral Drugs. Oxford, UK: Butterworth-Heinemann; 1997:805-835.
25.
Kauffman RE, O'Brien C, Gilford P. Sulfisoxazole secretion into human milk. J Pediatr. 1980;97:839-841.
26.
Walker PC. Neonatal bilirubin toxicity: a review of kernicterus and the implications of bilirubin displacement. Clin Pharmacokin. 1987; 13:26-50.
27.
Dillon AE, Wagner CL, Wiest D, Newman RB. Drug therapy in the nursing mother. Obstet Gynecol Clin. 1997;24:675-697.
28.
Sulfonamides. In AHFS Drug Information. Bethesda, Md: American Society of Health-System Pharmacists; 2000:755-766.
29.
Springer C, Eyal F, Michel J. Pharmacology of trimethroprimsulfamethaxazole in newborn infants. J Pediatr. 1982;100:647-649.
30.
Branski D, Kerem E, Gross-Kieselstein E, Hurvitz H, Litt R, Abrahamov A. Bloody diarrhea—a possible complication of sulfasalazine transferred through human breast milk. J Pediatr Gastroenterol Nutr. 1986;5:316-317.
31.
Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th ed.Baltimore, Md: Williams & Wilkins; 1998.
32.
American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 1994;93:137-150.
33.
Kucers A, Crowe SM, Grayson ML, Hoy JF: Tetracyclines. In Kucers A, et al., eds. The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, and Antiviral Drugs. Oxford, UK: Butterworth-Heinemann; 1997:719-762.
34.
American Academy of Pediatrics Committee on Drugs. Requiem for tetracyclines. Pediatrics. 1975;55:142-143.
35.
Kasten MJ. Symposium on antimicrobial agents—part XI: clindamycin, metronidazole, and chloramphenicol. Mayo Clin Proc. 1999;74:825-833.
36.
Trope GE, Lawrence JR, Hind VMD, Bunney J. Systemic absorption of topically applied chloramphenicol eyedrops. Br J Ophthalmol. 1979;63:690-691.
37.
Walker S, Diaper CJM, Bowman R, Sweeney G, Seal DV, Kirkness CM. Lack of evidence for systemic toxicity following topical chloramphenicol use. Eye. 1998;12:875-879.
38.
Fletcher C, Kakuda TN, Collier AC. Human immunodeficiency virus infection. In Di Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BR, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 4th ed.Stamford, Conn: Appleton and Lange; 1999:1930-1956.
39.
Eller MG, Smith RB, Phillips JP. Absorption kinetics of topical clindamycin preparations. Biopharm Drug Dispos. 1989;10:505-512.
40.
Barza M, Goldstein JA, Kane A, Feingold DS, Pochi PE. Systemic absorption of clindamycin hydrochloride after topical application. J Am Acad Dermatol. 1982;7:208-214.
41.
Borin MT, Powley GW, Tackwell KR, Batts DH. Absorption of clindamycin after intravaginal application of clindamycin phosphate 2% cream. J Antimicrob Chemother. 1995;35:833-841.
42.
Voron DA. Systemic absorption of topical clindamycin. Arch Dermatol. 1978;114:798-798.
Fredricsson B, Hagstrom B, Nord C, Rane A. Systemic concentrations of metronidazole and its main metabolites after intravenous, oral and vaginal administration. Gynecol Obstet Invest. 1987;24:200-207.
45.
Celiloglu M, Celiker S, Guven H, Tuncok Y, Demir N, Erten O. Gentamicin excretion and uptake from breast milk by nursing infants. Obstet Gynecol. 1994;84:263-265.
46.
Mann CF. Clindamycin and breast-feeding. Pediatrics. 1980; 66:1030-1041.
47.
O'Brien T. Excretion of drugs in human milk. Am J Hosp Pharm. 1974;31:844-854.
48.
Wilson JT. Milk/plasma ratios and contraindicated drugs. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia: ADIS Press; 1981:79-79.
49.
Tran JH, Montakantikul P. The safety of antituberculosis medications during breastfeeding. J Hum Lact. 1998;14:337-340.
50.
Snider DE, Powell KE. Should women taking antituberculotic drugs breast-feed?Arch Inter Med. 1984;144:589-590.
51.
Kelsey JJ, Moser LR, Jennings JJ, Munger MA. Presence of azithromycin breast milk concentrations: a case report. Am J Obstet Gynecol. 1994;170:1375-1376.
52.
Biaxin [package insert]. Chicago, Ill: Abbott; May 1999.
53.
Davey PG. The pharmacokinetics of clarithromycin and its 14-OH metabolite. J Hosp Inf. 1991;19 (suppl A):29-37.
54.
Dynabac [package insert]. Tewksbury, Mass: Muro Pharmaceuticals; October 1999.
55.
Sides GD, Cerimele BJ, Black HR, Bush U, DeSante KA. Pharmacokinetics of dirithromycin. J Antimicrob Chemoth. 1993;31(suppl C):65-75.
56.
Knowles JA. Drugs in milk. Pediatr Currents. 1972;21:28-32.
57.
Matsuda S. Transfer of antibiotics into maternal milk. Biol Res Pregnan Perinatol. 1984;5:57-60.
58.
Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-1399.
59.
Lassman HB, Puri SK, Ho I, Sabo R, Mezzino MJ, Pharmacokinetics of roxithromycin (RU 965). J Clin Pharmacol. 1988;28:141-152.
60.
Young RA, Gonzalez JP, Sorkin EM. Roxithromycin: a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1989;37:8-41.
61.
Gardner DK, Galbe SG, Garter C. Simultaneous concentrations of ciprofloxacin in breast milk and serum in mother and breast-fed infant. Clin Pharm. 1992;11:352-354.
62.
Cover DL, Mueller BA. Ciprofloxacin penetration into human breast milk. DICP. 1990;24:703-704.
63.
Giamerellou H, Kolokythas E, Petrikkos G, Gazis J, Aravantinos D, Sfikakis P. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med. 1989;87(suppl 5A):49S-51S.
64.
Harmon T, Burkhardt G, Appelbaum H. Perforated pseudomembranous colitis in the breast-fed Infant. J Pediatr Surg. 1992;27:744-746.
65.
Dan M, Weidekamm E, Sagiv r, Portmann R, Zakut H. Penetration of fleroxacin into breastmilk and pharmacokinetics in lactating women. Antimicrob Agents Chemother. 1993;293-296.
66.
Traeger A, Peiker G. Excretion of nalidixic acid via mother's milk. Arch Toxicol. 1980;S4:388-390.
67.
Belton ME, Jones VR. Hemolytic anemia due to nalidixic acid. Lancet. 1965;2:691-691.
68.
Murray EDS. Nalidixic acid in pregnancy. Br Med J. 1981;282:224-224.
69.
Wise R. Norfloxacin: a review of pharmacology and tissue penetration. J Antimicrob Chemother. 1984;13:59-64.
70.
Noroxin [package insert]. West Point, Pa: Merck & Co.; October 1999.
71.
Alghasham AA, Nahata MC. Clinical use of fluoroquinolones in children. Ann Pharmacother. 2000;34:347-359.
Chevalier X, Albengres E, Voisin MC, Tillement JP, Larget-Piet B. Acase of destructive polyarthropathy in a 17-year old youth following pefloxacin treatment. Drug Safety. 1992;7:310-314.
74.
Le LX, Fessard C, Noblet C, Ait SL, Moore N. Severe polyarthropathy in an adolescent treated with pefloxacin. J Rheumatol. 1991;18:1941-1942.
75.
Chang H, Chung MH, Kim JH, Kim JH. Pefloxacin-induced arthropathy in an adolescent with brain abscess. Scand J Infect Dis. 1996;28:641-643.
76.
Azad Khan AK, Truelove SC. Placental and mammary transfer of sulphasalazine. Br Med J. 1979;2:1553-1553.
77.
Smadel JE, Woodward TE, Ley HL Jr., Lewthwaite R. Chloramphenicol (Chloromycetin) in the treatment of Tsutsugamushi disease (scrub typhus). J Clin Invest. 1949;28:1196-1215.
78.
Havelka J, Hejzlar M, Popov V, Viktorinova D, Prochazka J. Excretion of chloramphenicol in human milk. Chemotherapy. 1968;13:204-211.
79.
Steen B, Rane A. Clindamycin passage into human milk. Br J Clin Pharmacol. 1982;13:661-664.
80.
Smith JA, Morgan JR, Rachlis AR, Papsin FR. Clindamycin in human breast milk. Can Med Assoc J. 1975;112:806-806.
81.
Erickson SH, Oppenheim GL, Smith GH. Metronidazole in breast milk. Obstet Gynecol. 1981;57:48-50.
82.
Passmore CM, McElnay JC, Rainey EA, D'Arcy PF. Metronidazole excretion in human milk and its effect on the suckling neonate. Br J Clin Pharmacol. 1988;26:45-51.
83.
Clements CJ. Metronidazole and breast feeding. NZ Med J. 1980;92:329-329.
