Some oral
antibiotics contain a pivalate
ester, because molecules with a pivalate entity show enhanced absorption in the intestine. Upon absorption, such a "
prodrug" is broken down into the active form of a given
antibiotic and a pivalate molecule, the latter of which is converted to
pivaloylcarnitine through pivaloyl-
CoA and is excreted in the urine. Long-term administration of drugs containing pivalate decreases blood
carnitine level and causes defects in
fatty acid oxidation. Here, we used liquid chromatography tandem mass spectrometry to measure
carnitine and
pivaloylcarnitine levels in two patients (Patient 1: 16-month-old boy and Patient 2: 18-month-old boy) with secondary
carnitine deficiency and
hypoglycemic convulsions caused by pivalate-containing
antibiotics. Both patients were administered excessive doses of pivalate for the long-term treatment of
recurrent infection, and consequently, the serum free
carnitine levels were very low (Patient 1: 1.0 micromol/L and Patient 2: 0.4 micromol/L), compared to normal range of 33.3-43.0 micromol/l, while the serum
pivaloylcarnitine levels were elevated from normally undetectable level (Patient 1: 3.7 micromol/L and Patient 2: 1.6 micromol/L). Patient 1 recovered immediately after the
glucose infusion, whereas Patient 2 remained symptomatic even after
blood glucose level was normalized and fully recovered after
carnitine supplementation. The urine
pivaloylcarnitine level in Patient 2 was increased during
carnitine supplementation (from 821.4 to 12,200 micromol/g
creatinine) even after discontinuing the
antibiotics, indicating that a considerable amount of pivalate was accumulated in the tissues. In conclusion, long-term administration of pivalate-containing
antibiotics should be avoided particularly in children.