Clostridioides difficile Treatment While Breastfeeding

Vancomycin

Vancomycin has been the first-line drug to treat CDI for many years. It has been studied in only one nursing mother. A single colostrum vancomycin level of 12.7 mg/L was found 4 hours after the end of the infusion of vancomycin 1 g intravenously given every 12 hours. ⁶ Assuming that the colostrum level is a peak level, an exclusively breastfed infant would receive a maximum of 1.9 mg/kg daily by mouth in breast milk. This dose is only about 5% of the oral vancomycin dose of 40 mg/kg daily used to treat CDI in infants. Because vancomycin is given by mouth, not intravenously, for CDI and is poorly absorbed orally, it is not likely to reach the bloodstream of the infant or cause any systemic adverse effects in breastfed infants, although gastrointestinal microbiota disruption is a possibility.

Fidaxomicin

Fidaxomicin is a macrolide antibiotic used specifically to treat CDI in a dose of 200 mg twice daily. It is mainly confined to the gastrointestinal tract after oral administration, with peak serum concentrations of 5 and 12 mcg/L for the drug and its active metabolite in adults. No information is available on the use of fidaxomicin during breastfeeding. Because of its minimal oral absorption, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants.

Metronidazole

Metronidazole has been fairly well studied in nursing mothers. With maternal intravenous and oral therapy, breastfed infants receive metronidazole in doses that are less than those used to treat infections in infants, although the active metabolite adds to the total infant exposure. Plasma levels of the drug and metabolite are measurable in infants, but are less than maternal plasma levels. Cases of Candida infections and diarrhea in breastfed infants have been reported, and a comparative trial suggested that oral and rectal colonization with Candida might be more common in breastfed infants exposed to metronidazole.

Because of the well-demonstrated genotoxicity and mutagenicity in bacteria, carcinogenicity in animals, and possible mutagenicity in humans, concern has been raised about exposure of healthy infants to metronidazole through breast milk. The relevance of these findings has been questioned and no definitive study has been performed in humans. Opinions vary among experts on the advisability of long-term metronidazole therapy while breastfeeding.

Rifaximin

Rifaximin is a poorly absorbed rifamycin that is only used orally for gastrointestinal infections. It is not likely to reach the breast milk or bloodstream of the infant or cause any adverse effects in breastfed infants after maternal use. However, no published experience exists with rifaximin during breastfeeding.

Bezlotoxumab

Bezlotoxumab is a monoclonal antibody that binds to C. difficile toxin B and neutralizes its effects. No information is available on the use of bezlotoxumab during breastfeeding. Similar to other monoclonal antibodies, bezlotoxumab is a large protein molecule. The amount in milk is likely to be very low and absorption is unlikely because it is probably partially destroyed in the infant's gastrointestinal tract. ⁷ Bezlotoxumab is not contraindicated in nursing mothers, but until more data become available, it should be used with careful infant monitoring during breastfeeding, especially while nursing a newborn or preterm infant.

Fecal microbiota transplantation

FMT involves transfer of fecal flora from a donor to a recipient's intestinal tract. FMT is considered for patients with severe and fulminant CDI with two or more recurrences refractory to antibiotic therapy.^3,4 The U.S. Food and Drug Administration has alerted practitioners of cases of transmission of pathogenic Escherichia coli from donor to FMT recipients, some of whom became ill and some of whom died. Transmission of COVID-19 infection to the recipient is a theoretical risk. No reports exist of nursing mothers receiving FMT, but direct transmission of bacteria from the mother's gastrointestinal tract to the infant through breast milk is unlikely.