unlike ceftazidime and cefoperazone, ceftriaxone does not have useful activity against Pseudomonas aeruginosa. It is generally not active against Enterobacter species, and its use should be avoided in the treatment of Enterobacter infections, even if the isolate appears susceptible, because of the emergence of resistance. Some organisms, such as Citrobacter, Providencia, and Serratia, have the ability to become resistant through the development of cephalosporinases (enzymes that hydrolyze cephalosporins and render them inactive). Available forms Ceftriaxone is available for administration via the intramuscular or the intravenous routes. Diluents containing calcium should not be used to reconstitute ceftriaxone, and it must not be administered in intravenous lines containing other calcium-containing solutions, as a ceftriaxone-calcium precipitate could form. Specific populations Pregnancy Ceftriaxone is pregnancy category B. It has not been observed to cause birth defects in animal studies, but a lack of well-controlled studies done in pregnant women exists. Breastfeeding Low concentrations of ceftriaxone are excreted in breast milk that are "not expected to cause adverse effects in breastfed infants." The manufacturer recommends that caution be exercised when administering ceftriaxone to women who breastfeed. Newborns Hyperbilirubinemic neonates are contraindicated for the use of ceftriaxone. It can compete with bilirubin and displace it from binding to albumin, increasing the risk of bilirubin encephalopathy. Elderly According to the package insert, clinical studies did not show differences in efficacy and safety of ceftriaxone in geriatrics compared to younger patients but "greater sensitivity of some older individuals cannot be ruled out." Adverse effects Although generally well tolerated, the most common adverse reactions associated with ceftriaxone are changes in white blood cell counts, local reactions at site of administration, rash, and diarrhea. Incidence of adverse effects greater than 1%: Eosinophilia (6%) Thrombocytosis (5.1%) Elevations in liver enzymes (3.1–3.3%) Diarrhea (2.7%) Leukopenia (2.1%) Elevation in BUN (1.2%) Local reactions: pain, tenderness, irritation (1%) Rash (1.7%) Some less frequently reported adverse events (incidence < 1%) include phlebitis, itchiness, fever, chills, nausea, vomiting, elevations of bilirubin, elevations in creatinine, headache and dizziness. Ceftriaxone may precipitate in bile, causing biliary sludge, biliary pseudolithiasis, and gallstones, especially in children. Hypoprothrombinaemia and bleeding are specific side effects. Haemolysis is reported. It has also been reported to cause post kidney failure in children. Like other antibiotics, ceftriaxone use can result in Clostridium difficile-associated diarrhea ranging from mild diarrhea to fatal colitis. Contraindications Ceftriaxone should not be used in those with an allergy to ceftriaxone or