Hypocarnitinemia Observed in an Infant Treated with Short-Term Administration of Antibiotic Containing Pivalic Acid

Abstract

Carnitine is a water-soluble amino acid derivative required for β-oxidation of long-chain fatty acids. In carnitine cycle abnormalities and low carnitine states, fatty acid β-oxidation is inhibited during fasting, resulting in hypoglycemia. Pivalic acid is a substance used in prodrugs to increase absorption of parent drugs, and antibiotics containing pivalic acid are frequently used as wide spectrum antibiotics for pediatric patients in Japan. Pivalic acid released after absorption is conjugated with free carnitine to form pivaloylcarnitine, which is then excreted in urine. As a consequence, long-term administration of pivalic acid containing antibiotics has been associated with depletion of free carnitine, inhibition of energy production and subsequent hypoglycemia. Here we report a case of a 23-month-old boy treated with an antibiotic containing pivalic acid for 3 days for upper respiratory tract infection. Laboratory data at referral indicated hypoglycemia, decreased free carnitine and elevated five-carbon acylcarnitine. Isomer separation confirmed the major component of increased five-carbon acylcarnitine to be pivaloylcarnitine, thereby excluding the possibility of a genetic metabolic disorder detected with similar acylcarnitine profile. The level of carnitine was normal when the antibiotic was not administered. Our case shows that the use of antibiotics containing pivalic acid in young children requires consideration of hypocarnitinemia, even with short-term administration.

Research on the Clinical Practical Use of Pivoxil-Conjugated Antibodies and the Risk of Carnitine Deficiency Using Real-World Data

“…Additionally, our survey revealed that carnitine deficiency-related AEs occurred not only during the initial phase of treatment but also persisted throughout long-term therapy (Tables 3 and 4). This finding is consistent with the observations reported in previous studies [6][7][8][9][10]24]. Therefore, a careful consideration of the risk given the potential for AEs to manifest throughout the entire treatment course is essential when administering PV.…”

“…While case reports have documented the actual prescription of PV to children, the occurrence of carnitine deficiency related to its administration, and subsequent treatment strategies [6][7][8][9][10], a large-scale survey has not yet been conducted. Additionally, although a report explored the link between PV and hypoglycemia in children [11], no large-scale studies have directly evaluated the risk of carnitine deficiency itself compared to other antibiotics.…”

A pilot study of serum free carnitine levels in hospitalized febrile children

“…Currently, the relationship among PCA use duration, carnitine deficiency, and acute encephalopathy/hypoglycemia remains unclear. Some previous studies showed that even short‐term PCA treatment may be unsafe 4,5 …”

“…Some previous studies showed that even short-term PCA treatment may be unsafe. 4,5 We did not expect to record high FC values in six of 100 children with febrile illnesses; all but one were diagnosed with KD. Although the reason why the FC level is high in children with KD remains unclear, we presume this may reflect tissue damage related to systemic inflammation in patients with KD.…”