New Antimicrobials and Breastfeeding

Cephalosporins

Because of the safety of cephalosporins, they are considered acceptable to use during breastfeeding. Older cephalosporins do not achieve high levels in breast milk. All of the new cephalosporins are given intravenously and probably have low oral bioavailability. These cephalosporins have very broad spectrums, so there is greater concern about gastrointestinal effects in the infants. A rare occurrence with cephalosporins is allergic reactions in the infant. Toxic epidermal necrolysis was recently reported in a breastfed infant whose mother began taking cephalexin. The infant had apparently been sensitized by a prior course of cefazolin for a urinary tract infection. ⁴

Cefiderocol is used for treatment of complicated urinary tract infections caused by susceptible gram-negative bacteria in adults who have limited or no alternative treatment options. It is active in vitro against a variety of multidrug-resistant gram-negative bacilli, including Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Ceftaroline is FDA approved for complicated skin and skin structure infections and community-acquired pneumonia caused by susceptible gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). Ceftolozane–tazobactam is a cephalosporin-beta-lactamase inhibitor combination used to treat complicated intra-abdominal and urinary tract infections as well as hospital-acquired or ventilator-associated pneumonia. It has a very broad spectrum, including many antibiotic-resistant organisms.

Fluoroquinolones

Delafloxacin is a new fluoroquinolone indicated for skin infections and community-acquired pneumonia. It is administered intravenously and is about 84% plasma protein bound, indicating that excretion into milk is likely to be low. Delafloxacin is about 59% absorbed orally and absorption by a breastfed infant may be even lower because of the calcium in milk. Breastfeeding is not considered to be contraindicated during its use.

Tetracyclines

Several new tetracyclines have become available recently, generally for organisms resistant to older antibiotics. Although a theoretical risk for tooth discoloration exists, no cases have ever been reported in breastfed infants whose mothers were taking a tetracycline. The lack of cases is probably because the amounts in milk are low, treatment courses are usually short, and oral absorption is inhibited by breast milk calcium. Another factor is their differential binding to cations. For example, doxycycline has low calcium binding and is now considered safe to use in children. Minocycline binds iron extensively and forms a black compound that has been found in breast milk. ⁵ The main theoretical concern with maternal use of tetracyclines during breastfeeding is prolonged or repeated courses, but courses of around 2 weeks are considered to be low risk with older tetracyclines.

Eravacycline is a broad-spectrum antibiotic that has activity against Bacteroides sp., several gram-negative organisms and MRSA. It is indicated for complicated intra-abdominal infections in doses of 2 mg/kg per day for 4–14 days. It is unknown how much eravacycline is excreted into breast milk, but the drug is 79–90% bound to plasma proteins, so milk levels are probably low. Although the manufacturer states that breastfeeding is not recommended during treatment and for 4 days after the last dose, it is unlikely that short-term use of eravacycline would pose a great risk of harm to the breasted infant.

Omadacycline has a broad spectrum, including many tetracycline-resistant organisms. It is indicated for community-acquired pneumonia and skin infections in a daily dosage of 100 mg intravenously or 300–450 mg daily by mouth for 7–14 days after a single loading dose. It is unknown how much omadacycline is excreted into breast milk, but the drug is only about 35% absorbed orally under optimal circumstances; absorption is probably less from milk because of its calcium content. As with eravacycline, the manufacturer states that breastfeeding is not recommended during treatment and for 4 days after the last dose.

Sarecycline is indicated only for moderate to severe acne caused by Propionibacterium acnes. As such, it is taken for 12 weeks or longer in a dose of 150 mg daily. Such prolonged courses of tetracyclines are not recommended because even a small fraction absorbed by the infant from milk could have a cumulative staining effect on the infant's permanent teeth.

Oxazolidinone

Tedizolid is in the same class as linezolid. It is FDA approved for complicated skin and skin structure infections caused by susceptible gram-positive organisms, including MRSA. It is given once daily for 6 days. Compared with linezolid, it is less likely to cause thrombocytopenia and to inhibit monoamine oxidase. Tedizolid is 70–90% bound in maternal plasma, so large amounts are not expected to appear in breast milk. It is not contraindicated during breastfeeding.

Glycopeptides

Dalbavancin, telavancin, and oritavancin are new drugs in the same drug class as vancomycin. They all have rather narrow spectrums limited primarily to gram-positive organisms, including MRSA. All are given intravenously, and have poor oral absorption, so they are unlikely to have systemic adverse effects in breastfed infants. Dalbavancin and telavancin are 93% plasma protein bound, so amounts in milk are likely very low. Oritavancin's plasma protein binding is a little lower at 85%, but still extensive, so milk levels are also likely to be low. None are considered to contraindicate breastfeeding.

Pleuromutilin

Lefamulin is the first marketed pleuromutilin antibiotic. It binds to the peptidyl transferase center of the 50S subunit of the bacterial ribosome, inhibiting bacterial protein synthesis. It is not cross-resistant with antibiotics in other classes. Lefamulin is approved for treatment of community-acquired bacterial pneumonia in adults. It is given orally or intravenously for 5–7 days. No information is available on the use of lefamulin during breastfeeding, but it is 95–97% plasma protein bound, so amounts in milk are likely very low. In addition, its oral bioavailability is only 25%, so the amount reaching the infant's systemic circulation is also probably low. However, the manufacturer recommends that mothers should avoid breastfeeding during treatment and for 2 days after the final dose. Until more information becomes available, an alternate drug might be preferred, especially while nursing a newborn or preterm infant.

Antiparasitics

Moxidectin is an antiparasitic agent for the treatment of onchocerciasis or river blindness. No information is available on the clinical use of moxidectin during breastfeeding, but it has been measured in the milk of 12 lactating women who had weaned their infants. They were given moxidectin 8 mg orally as a single dose. Milk samples were collected for at least 30 days, and in some, at various times for up to 90 days after a single dose of 8 mg. The cumulative amount of drug excreted into breast milk averaged 0.056 mg for the study period, which was 8.7% of the weight-adjusted maternal dose. ⁶ Until more data become available, moxidectin should be used with close infant monitoring for gastrointestinal side effects during breastfeeding, especially while nursing a newborn or preterm infant.

Tafenoquine succinate is a long-acting analog of primaquine used to treat malaria. It is given as a single dose of 300 mg to treat Plasmodium vivax or, off label, ovale. It is also used for malaria prophylaxis in a dosage regimen of 200 mg orally once daily for 3 days before travel as a loading regimen. This is followed by 200 mg orally once weekly starting 7 days after the last loading dose and continuing during travel to malarious area as maintenance regimen, then 200 mg PO once at 7 days after the last maintenance dose in the week after exit from malarious area. Tafenoquine may be administered continuously for up to 6 months.

No information is available on the use of tafenoquine during breastfeeding, but it can cause hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. If tafenoquine is needed by the mother, testing both the mother and infant for G6PD deficiency is required before the drug is given. Tafenoquine is contraindicated in breastfeeding women when the infant is G6PD deficient or the infant's G6PD status is unknown. Because the half-life of tafenoquine averages 15 days, the manufacturer recommends that mothers should not breastfeed for 3 months after the last dose if the infant is G6PD deficient.