Antibiotics and lactation: An overview of relative infant doses and a systematic assessment of clinical studies

Abstract

Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling. The infant exposure has been calculated and expressed as a percentage of a normal infant therapeutic dose. Sixty-six studies were included in five antibiotic groups (broad-spectrum penicillin, cephalosporins, macrolides and lincosamides, quinolones and sulphonamides). Cephalosporins were the most studied group of antibiotics (n = 21). Fifteen studies met all the criteria of "mother exposure to antibiotic". Six studies met every criterion related to "plasma sampling". Only one case report met all listed criteria for lactation studies. The correct calculation of infant exposure to antibiotics via the milk:plasma ratio (AUC) varies between 13% for macrolides and 38% for broad-spectrum penicillin. The highest assessed exposure as a percentage of infant therapeutic dose was for metronidazole (11%). The studies meet to a limited extent with the quality standards for lactation research. The breastfed infants are exposed to a subtherapeutic concentration of antibiotics.

Ceftriaxone: clinical review, consumption in Portugal and safety alerts

“…(24) Ceftriaxone has a plasma protein binding of 83% to 96%, which is variable with concentration. (4,6,9,(22)(23)(24)(25)(26)(27)(28)(29) This cephalosporin is distributed in: synovial fluid (mean of 14 mg/L after 1 g IV at 24 hours) and peritoneal (mean of 15.3 to 20.1 mcg/ml after 1 g IM at 12 hours), saliva and respiratory tract mucus (mean 1.54 to 2.16 mcg/ml after 1 g IM/day for 7 days), bronchial tissue (mean 11.2 ± 5.7 mcg/ml after 1 g IV at 12 hours), aqueous humor (median 2.27 mcg/ml after 2 g IV at 2 hours), cerebrospinal fluid (mean 20 mcg/ml after 100 mg/kg at 2 hours), hepatic tissue (mean 130 mg/ kg after 1 g IV at 12 hours), pulmonary and bronchial inflammation (mean 31.8 mcg/ml after 2 g IV at 1 to 2 hours), middle ear (mean 35 mcg/ml after 50 mg/kg at 24.3 hours), placenta (mean 19.6 to 40.6 mcg/ml) and prostate gland (mean 1 to 50 mcg/ml after 2 g IV at 4 hours). (4,6,9,11,16,(22)(23)(24)(25)(26)(27)(28)(29)…”

“…In critical patients, the pharmacokinetic parameters of ceftriaxone are altered, thus monitoring of serum concentration is recommended. (4,6,9,11,16,(22)(23)(24)(25)(26)(27)(28)(29) Distribuição A área sob a curva (AUC) em doentes com a função renal normal é de 551 ± 91 mcg×h/ml (500 mg IV), de 1006 ± 118 mcg×h/ml (1 g IV) e de 1703 ± 203 mcg×h/ ml (2 g IV). (24) A ceftriaxona tem uma ligação às proteínas plasmáticas de 83% a 96%, que é variável com a concentração.…”

“…(4,6,9,(22)(23)(24)(25)(26)(27)(28)(29) Esta cefalosporina distribui-se no: líquido sinovial (média de 14 mg/L após 1 g IV às 24 horas) e peritoneal (média de 15,3 a 20,1 mcg/ml após 1 g IM às 12 horas), saliva e muco do trato respiratório (média de 1,54 a 2,16 mcg/ml após 1 g IM/dia durante 7 dias), tecido brônquico (média 11,2 ± 7,9 mcg/ml após 1 g IV às 12 horas), humor aquoso (média 2,47 mcg/ml após 2 g IV às 2 horas), fluido cerebrospinal (média 20 mcg/ml após 100 mg/kg às 2 horas), tecido hepático (média 130 mg/kg após 1 g IV às 12 horas), pulmonar e brônquico inflamado (média 31,8 mcg/ml após 2 g IV às 1 a 2 horas), ouvido médio (média 35 mcg/ml após 50 mg/ kg às 24,3 horas), placenta (média 19,6 a 40,6 mcg/ml) e glândula prostática (média 1 a 50 mcg/ml após 2 g IV às 4 horas). (4,6,9,11,16,(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) Volume de Distribuição O volume de distribuição (Vd) é dose dependente e varia entre 5,78 e 13,5 L. (4) Foram observados os seguintes volumes de distribuição da ceftriaxona: 6,40-9,73 L (500 mg IV), 7,21-10,58 L (1 g IV), e 8,87-11,85 L (2 g IV). Nos doentes críticos, os parâmetros farmacocinéticos da ceftriaxona encontram-se alterados, pelo que se recomenda a monitorização da concentração sérica do antibiótico.…”

“…(4,9,11,16) Concentration of ceftriaxone in breast milk was 3 to 4% in comparison to serum concentration in women breastfeeding after IV and IM administration of 1g of ceftriaxone 3 days postpartum. (25)…”

“…(4,9,11,16) Após administração IV e IM de 1 g de ceftriaxona 3 dias após o parto em mulheres a amamentar a concentração do antibiótico no leite materno foi de 3 a 4% relativamente à concentração sérica. (25)…”