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Home , Nitrofurantoin

From the Clinical Inquiries Family Physicians Inquiries Network

Jessica Kaiser, MD, Which UTI therapies Vanessa McPherson, MD, and Leonora Kaufmann, are safe and effective MLIS Carolinas Medical Center, during breastfeeding? Charlotte, NC

Evidence-based answer / (TMP/SMX) extrapolation from case series and has a high success rate in eradicating disease-oriented outcomes). for women with urinary tract A 7-day course of nitrofurantoin infection and is compatible with breastfeed- has similar efficacy to TMP/SMX and ing (strength of recommendation: C, based is compatible with breastfeeding, but it on extrapolation from studies with nonlactat®- Dowdenshould be avoided Health in populations Media at risk ing women and disease-oriented outcomes). for glucose-6-phosphate dehydrogenase Quinolones (, ) (G6PD) deficiency (also known as are effective and probablyCopyright compatibleFor personalfavism, most often use found only in patients with breastfeeding; however, their use has of Mediterranean or African descent) not been recommended by many inves- (SOR: C, extrapolation from studies in tigators based on arthropathy in animal nonlactating women and disease-oriented fast track studies (SOR: C, based on outcomes). Safety data Clinical commentary for quinolones An that’s effective for mom antibiograms or make them available on a in infants and safe for baby is of paramount semiannual or annual basis. Keeping these and children importance readily available can be a time-saver when Knowing the local resistance patterns can it comes to decision-making and writing a are mixed greatly aid in choosing a safe, effective prescription. antibiotic. Most local laboratories that Timothy Huber, MD do microbiology work either publish their Oroville, Calif z Evidence summary lation, studies of antibiotic penetration Urinary tract infections (UTIs) are com- into breast milk, and effects of antibiot- mon in reproductive-aged women. In ics given to infants directly. lactating women, it’s important to select a therapy that is not only effective, but How the efficacy of UTI also safe for the breastfeeding infant. No treatments stack up studies in the literature address the safety The best evidence for efficacy of UTI or efficacy of UTI treatments in lactat- treatments comes from a 1999 meta- ing women and their infants. Therefore, analysis of uncomplicated UTI in non- recommendations are extrapolated from pregnant, nonlactating women.1 They studies of efficacy in the general popu- found TMP/SMX to be the most widely

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For mass reproduction, content licensing and permissions contact Dowden Health Media. es i r i qu

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I studied antibiotic and to have a 93% A final case series administered cipro- bacterial eradication rate; it was there- floxacin 750 mg, 400 mg, or al

c fore used as a standard for comparison ofloxacin 400 mg twice daily to 3 groups of other treatments. Nitrofurantoin and of 10 women each.5 Milk samples were quinolones (ofloxacin, ciprofloxacin, and obtained 6 times over 24 hours follow- Clini others) had comparable eradication rates ing the third dose of antibiotic. Maximum to TMP/SMX in the same study; 7-day levels in breast milk occurred 2 hours after courses of nitrofurantoin were more ef- the dose, and were 3.79, 3.54, and 2.41 ficacious than shorter ones. TMP/SMX is mcg/mL for ciprofloxacin, pefloxacin, and not recommended if the local resistance ofloxacin respectively. All 3 quinolones rate is more than 10% to 20%.2 achieved higher concentrations in breast Three-day therapy for uncomplicated milk than in serum. UTI is more effective than single-dose therapy and equal to longer courses for But are these drugs most .1 A longer course (7 days) safe for children? may be required for nitrofurantoin. Beta- While TMP/SMX and nitrofurantoin are lactams are associated with high levels of generally considered safe when given to resistance and therefore not recommended infants and children (barring G6PD de- in empiric treatment of UTI.2 ficiency), data are mixed regarding the safety of quinolones. Ciprofloxacin’s FDA A look at penetration indication for pediatric patients is limited into breast milk to postexposure anthrax prophylaxis due Most of the data regarding antibiotic to evidence of fluoroquinolone-induced penetration into breast milk come from joint toxicity in animal studies.6 Despite case series. One South African series this, they have been prescribed to tens of measured breast milk levels of both tri- thousands of children for select scenarios methoprim and sulfamethoxazole among such as chemotherapy-induced immuno- 50 Bantu women treated with TMP/SMX compromise, cystic fibrosis, complicated fast track for various infections (including UTI).3 UTIs, and salmonella infections.7 Three-day therapy The women received 160 mg TMP and A report was published summariz- 800 mg SMX 2 or 3 times daily for up ing safety data from the Bayer database for uncomplicated to 5 days. The average level of TMP in of compassionate use of ciprofloxacin.8 UTI is comparable breast milk was 2 mcg/mL, and the level The report indicates that 2030 treatment with longer of SMX was 4.7 mcg/mL. Researchers courses of ciprofloxacin were given to courses for most calculated that the average breastfeeding 1795 children up to age 17 for a variety infant would ingest only 1 mg of TMP of infections; only 3% were under age 5. antibiotics and 2.5 mg of SMX per day. TMP/SMX Most patients received 21 to 40 mg/kg is generally considered safe for infants in of ciprofloxacin per day; treatment dura- the absence of G6PD deficiency. tion was from 1 to 303 days. Arthralgia In a case series, 9 lactating mothers occurred in 1.5% of patients, most of were given nitrofurantoin 100 mg orally whom had cystic fibrosis. Of the 31 pa- every 6 hours for 1 day.4 On day 2, after a tients affected, arthralgias resolved in 25, single 100 to 200 mg dose, drug levels in improved in 1, and remained unchanged the breast milk 2 hours post-dose ranged in 1. (Data regarding resolution were un- from none (in 6 of the 9 women) to a max- available for 4 patients.) imum of 0.5 mcg/mL in one. Since even a very small amount of the drug may trigger Recommendations from others a hemolytic reaction among G6PD-defi- The American Academy of Pediatrics’ cient individuals, the researchers called for Committee on Drugs considers the fol- caution when prescribing to mothers from lowing antibiotics typically used for UTI high-risk populations. to be compatible with breastfeeding:

226 vol 56, No 3 / march 2007 The Journal of Family Practice CME es i r i qu

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I ciprofloxacin, ofloxacin, nitrofurantoin (caution for infants with G6PD deficien- al 9

c cy), and TMP/SMX. Drugs in Pregnancy and Lactation considers trimethoprim and sulfamethox- Clini azole to be compatible with breastfeeding “Do you EBP?” but cautions against sulfamethoxazole use in infants with known G6PD deficiency. The authors categorize nitrofurantoin, Evidence-based medicine from a ciprofloxacin, and ofloxacin as “probably team you trust—a monthly compatible/limited human data,” and ad- newsletter published by and vise caution with nitrofurantoin for in- for family physicians fants with G6PD deficiency.10 n z Transforming Practice, References plus updates 1. Warren JW, Abrutyn J, Bebel, R, et al. Guidelines When the evidence points to a change in for antimicrobial treatment of uncomplicated acute practice, we explain why bacterial cystitis and acute in wom- en. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 1999; 29:745–758 z Editor’s News Alert 2. Gupta, K, scholes D, stamm WE. Increasing Keep up with the latest in the world of prevalence of antimicrobial resistance among uro- pathogens causing acute uncomplicated cystitis in healthcare, always staying focused on the women. JAMA 1999; 281:736–758. evidence 3. Miller RD, Salter AJ. The passage of trimethoprim/ sulfamethoxazole into breast milk and its signifi- z cance. Proceedings of the 8th International con- The Help Desk Answers series gress of Chemotherapy, Athens. Hellenic Soc Che- Concise answers to your relevant mother 1974; 1:687–691. clinical questions 4. Varsano, I, Fischl, J, Shochet, S. The of orally ingested nitrofurantoin in human milk [letter]. z J Pediatr 1973: 886–887. Drug Profile Objective reviews of the drug messages fast track 5. Giamerellou h, Kolokythas e, Petrikkos G, et al. of three newer quinolones in targeting physicians and patients in the pregnant and lactating women. Am J Med 1989; media and on the Internet Avoid SMX in 87 (Suppl 5A):49s–51s. infants with known 6. Cipro package insert. West haven, conn: Bayer PLUS GSPD deficiency Pharmaceuticals Corporation; January 2004. 7. Grady R. Safety profile of quinolone antibiotics in z Behavioral Health Matters the pediatric population. Pediatr Infect Dis J 2003; 22:1128–1132. z Ever-expanding exclusive 8. Hampel B, Hullmann, R, Schmidt H. Ciprofloxacin content in pediatrics: worldwide clinical experience based on compassionate use-safety report. Pediatr Infect z 3 CME credits monthly Dis J 1997; 16:127–1209. 9. American academy of Pediatrics committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108:776–789. 10. Briggs, GG, Freeman rK, Yaffe sJ. Drugs during Pregnancy and Lactation. 7th ed. Baltimore, md: Lippincott, Williams & Wilkins; 2005.

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