Gram-positive organisms including coagulase-negative staphylococci are the most common causative organisms of late-onset sepsis in infants [1]. Daptomycin is a cyclic lipopeptide antibiotic that provides an activity against gram-positive pathogens, including vancomycin-resistant organisms [2]. Daptomycin has been approved for the treatment of complicated skin and skin structure infections and bacteraemia caused by
A 25-week male infant with a birth weight of 750 g was delivered by an emergency caesarean section to a 40-year-old mother. There was no evidence of chorioamnionitis. A course of steroid had been given. His Apgar score was 2 and 5 at 1 and 5 minutes, respectively. Soon after delivery, the baby was transferred to the neonatal intensive care unit, received surfactant and was connected to a mechanical ventilator. An umbilical venous catheter was inserted, a blood culture sent and antibiotics with ampicillin and gentamicin were started. Later, a brain ultrasound was done and showed grade II of intraventricular haemorrhage. The transthoracic echocardiogram was also done on the fifth day of life, showing large patent ductus arteriosus. Thus, one course of ibuprofen was given. At the age of seven days, antibiotics were changed to vancomycin and cefotaxime. At ten days of life, the baby developed a perforated jejunum. The blood culture result came back positive with
Additionally, the prothrombin time (PT) was 56.1 seconds, the international normalised ratio (INR) was 6.19 and the partial thromboplastin time was 169.9 seconds. Written inform consent was obtained from family. To investigate other potential causes of liver damage, a urine culture for cytomegalovirus was performed, and the result was negative. Additionally, an abdominal ultrasound was done, and the result documented normal hepatic anatomy. The patient died with 48 hours of daptomycin initiation.
The above case is the first that enlightens the possible rare and serious ADR associated with daptomycin therapy in infants. Daptomycin is active against gram-positive bacteria [2]. The mechanism of action involves binding to bacterial membranes causing depolarisation. As a result, a rapid inhibition of protein, DNA, and RNA synthesis results in bacterial cell death [6]. Pharmacokinetics and pharmacodynamics studies of daptomycin in infant populations have not been studied extensively. Thus, data are still limited on the optimum dosing regimen of daptomycin in infants [7,8]. Bradley et al. conducted a single dose pharmacokinetics study of daptomycin in 19 infants aged between 3 months and 24 months [7]. Cohen-Wolkowiez et al. conducted the same study in infants younger than 120 days. [8]. Preliminary results showed an inverse linear correlation exists between clearance of daptomycin and age [4,7,8]. Daptomycin elimination occurs primarily through the renal system, with 50% of the administered dose excreted within 24 h as unchanged drug. Neonates and infants had higher clearance rates compared with adults and adolescents. The mean clearance rate is 21 mL per h per kg in neonates and 11 mL per h per kg in children [4]. This can explain why higher doses are needed to achieve the warranted therapeutic drug concentration in infants and younger children [9]. The available mounting literature indicate that daptomycin is well tolerated in infants. Common ADRs, including mild CPK and transaminase increase, headache, phlebitis, and local reactions, are reported in comparable or lower rates compared with adults’ series [4,5]. Animal data on neonatal dogs showed serious adverse efects on muscular, neuromuscular and/or nervous systems. As a result, daptomycin is not approved for use in neonates and infants younger than one year [3]. In addition, the product labels an elevation of PT and INR as rare and uncommon ADRs, respectively [3]. Our case initially received an appropriate therapy with vancomycin plus rifampin. However,
Although daptomycin appears to be an effective and safe alternative therapy in infants with invasive gram-positive infection, our case highlights that foetal hepatotoxicity associated with DIC can be observed with the administration of intravenous daptomycin at a dose of 6 mg per kg every 12 h in infants. Further studies are needed to gain knowledge about the pharmacokinetics, pharmacodynamics, as well as safety and efficacy of this drug in infants.