The pivoxil group is a simple branched-chain carboxylic acid with a tertiary-butyl group that has been applied to the design of pharmaceutical prodrugs of antibiotics such as a cephem antibiotic to increase the absorption and the bioavailability. In Japan, many these antibiotics such as cefcapene pivoxil, cefditoren pivoxil, cefteram pivoxil, tebipenem pivoxil, and pivmecillinam are approved and widely used to treat acute upper respiratory tract infection and acute otitis media. Pivoxil group is released by intestinal esterase and bind with carnitine and is excreted from the kidney as pivaloylcarnitine and sometimes causes carnitine deficiency. Many case reports were reported these carnitine deficiency with hypoketotic glycemia, seizure, coma, and hyperammonemia in Japan. In this chapter, these clinical case reports are introduced and discussed about related regulatory science issues.