Anti-infectives

4.4.1

Penicillins, cephalosporins and other β-lactam antibiotics

The M/P ratio of all the commonly used penicillin derivatives is under 1. As a rule, the exclusively breastfed infant receives considerably less than 1% of a therapeutic dose (survey in ). Similarly, this also applies for the cephalosporins, which are, to some extent, inactivated in the infant’s intestine (survey in ).

asked 67 breastfeeding mothers, who were taking amoxicillin in combination with clavulanic acid , about side-effects in their breastfed children. Symptoms were reported more frequently (22%) than with amoxicillin therapy alone. The symptoms were dose-dependent, but did not need any intervention. In another group, which took cefuroxim while breastfeeding, mild side-effects were reported in just under 3% of the cases, which was no more frequently reported than in a control group with cefalexin .

With sulbactam , the relative daily dose transmitted was a maximum of 1% ( ). With aztreonam , a 0.2% relative dose was reported for the baby at the next breastfeeding after the mother had taken a single dose ( ).

In a Japanese study on imipenem plus cilastatin , an average of 0.8% of a weight-related intravenously administered dose was measured in the daily amount of milk. Cilastatin was not detectable in the breastfed children ( ).

After administration of 1,000 mg meropenem every 8 hours, the maximum concentration in milk was 0.64 μg/mL; the infant weight-adjusted percentage of maternal dose was 0.18% ( ).

There are insufficient data on the breastfeeding period for the β-lactamase inhibitor, tazobactam , and the newer carbapenems ( doripenem and ertapenem ). Up to now, there have been no reports of toxic effects in the breastfed baby. The last-mentioned substances are scarcely absorbed. This argues against a biological availability to the breastfed baby.

4.4.2

Erythromycin and other macrolides

With erythromycin (M/P ratio about 0.5), the infant whose mother takes 2 g/day, receives a maximum of 0.48 mg/kg/day – just 2% of a weight-related therapeutic infant dose ( ). Pyloric stenosis, possibly caused by erythromycin via the mother’s milk, has been reported ( , ), but a causal relationship has not been confirmed. asked 55 breastfeeding mothers, who were treated with macrolides, about side-effects in their breastfed babies. Some 12% observed mild symptoms such as thinner stools or a skin rash, which, by comparison to amoxicillin , did not occur more frequently. In particular, no pyloric stenosis was observed.

In a case report on azithromycin (500 mg/day), a peak value of 2.8 mg/L of milk was cited. This represents 5% of the weight-related maternal dose ( ).

With 500 mg/day of clarithromycin , used to treat a puerperal infection, a maximum of 1.5 mg of the active substance per liter of milk was measured ( ). That is 2.7% of the maternal dosage per kg of bodyweight.

With roxythromycin , less than 0.05% is thought to pass into the milk ( ).

There are no data on the breastfeeding period for dirithromycin , josamycin , midecamycin , spiramycin , troleandomycin , and the ketolide telithromycin . There are no reports of specific intolerance during breastfeeding to any of the macrolides described here.

4.4.3

Tetracyclines

The older tetracyclines reach concentrations in the mother’s milk that are significantly below the maternal plasma values. In addition, the calcium ions in the mother’s milk reduce the absorption of the drug. There are no reports of breastfed infants having symptoms when mother is taking tetracyclines. In particular, there is no discoloration of the teeth as a result of exposure via mother’s milk.

With doxycycline therapy initially with 200 mg followed by 100 mg after 24 hours, a maximum of 1.4 mg/L was detected in the milk ( ).

One case report describes a brownish-black coloring of the milk after long-term intake of minocycline. Macrophages with iron-containing pigments were found in the milk. The authors believe that this is an iron chelate of minocycline or of a metabolite ( ).

There is insufficient data on the breastfeeding period for the glycylcycline , tigecycline . The limited oral bioavailability of tigecycline, however, argues against an appreciable intake by the breastfed infant.

4.4.4

Sulfonamides and trimethoprim

Sulfonamides pass into the mother’s milk in various amounts. The percentage specifications, based on the weight-related maternal dosage, vary between 1 and over 50% (in the case of the old sulfonamide sulfanilamide).

Trimethoprim and sulfamethoxazole , used in combination in co-trimoxazole , are excreted in breast milk in small amounts. With the usual dose of trimethoprim 320 mg and sulfamethoxazole 800 mg daily, an exclusively breastfed infant would be expected to receive 0.3 mg/kg/day of trimethoprim and 0.68 mg/kg/day of sulfamethoxazole, which is much lower than the recommended dosage for children ( ).

Since sulfonamides compete with bilirubin for albumin binding sites, there might be a risk of an increase in the newborn’s bilirubin.

4.4.5

Quinolones

Insofar as they have been studied at all, nalidixic acid and the newer fluoroquinolones go into the mother’s milk.

With ciprofloxacin , it has been calculated that between 2 and 7% of the weight-related maternal dose reaches the infant ( , ). No ciprofloxacin could be detected in the serum of a breastfed baby (maternal serum concentration 0.21 mg/L, detection limit 0.03 mg/L; ).

With levofloxacin , a mother received 500 mg/day over 3 weeks, first administered parenterally and then orally, maximum concentrations in the milk of 8.2 mg/L (5 hours after administration) and, at most, a relative dose of 15% were calculated for an exclusively breastfed baby ( ).

There are no data on the transfer of enoxacin , lomefloxacin , moxifloxacin , nadifloxacin , norfloxacin , ofloxacin and sparfloxacin into mother’s milk.

In animal research, quinolones irreversibly damage the cartilage in the joints of juvenile animals. This has not as yet been observed with exposure to quinolones via the mother’s milk.

4.4.6

Nitrofurans and drugs for urinary tract infections

With nitrofurantoin , after a single dose of 100 mg to four women, an average of 1.3 mg/L and a maximum (about 5 hours after administration) of 3.2 mg/L was measured in the milk. An M/P ratio of 6 was calculated ( ). Based on these values, the relative dose for an exclusively breastfed baby can reach 10%. Older investigations only reported 2.5% ( ). Nitrofurantoin inhibits the glutathione reductase and should, therefore, be used cautiously for breastfeeding mothers of newborns with hyperbilirubinemia or glucose-6-phosphate-dehydrogenase deficiency.

One study estimated the exposure of nifurtimox through milk using computer simulation ( ). This population pharmacokinetic analysis calculated that a breastfed infant would receive less than 10% of the maternal weight adjusted dose. In a study with 33 infants whose mothers took nifurtimox, no serious adverse events were reported in any of the breastfed infants ( ).

The locally used nitrofurans, furazolidone and nitrofural , as well as nifuratel are insufficiently investigated for the breastfeeding period, and are not among rational drug therapies. The same applies for nifuroxazide, which is used for diarrhea. For the same reasons, the urinary tract medications, methenamine and nitroxoline should be avoided during breastfeeding.

The limited experience with fosfomycin during breastfeeding permits the assumption that only a limited amount of the active ingredient passes into the mother’s milk.

4.4.7