Dose:    15 mg/kg IV as loading dose
              7.5 mg/kg/dose maintenance dose IV, PO
              See comments before using

Frequency: See comments for first dose after loading
                     Q 8 hours in term infants
                     Q 12 hours in preterm infants             
                      Adjustments for hepatic or renal failure.

Comments: Metronidazole is antibiotic used to treat anaerobic organisms including Bacteroides species.  The drug is 80% metabolized in the liver, though metabolites and unchanged metronidazole are predominantly excreted in the urine. Dosage modification (i.e., increased interval to every 12 hours) does not appear necessary unless the infant has significant hepatic dysfunction or prematurity. Current recommendations for term infants are to give a 15 mg/kg loading dose and to begin a maintenance dose of 7.5 mg/kg every 8 hours beginning 24 hours after the loading dose. For preterm infants, a loading dose of 15 mg/kg is given, but the first maintenance dose of 7.5 mg/kg is started 48 hours later. The interval between doses in preterm infants is 12 hours . There are scattered reports in the pediatric literature noting its use. It appears to be the best drug for the treatment of B. fragilis meningitis, superior to clindamycin, chloramphenicol, and cefotaxime (although cefotaxime has good CSF penetration, resistance frequently develops). The anecdotal reports did not note any significant adverse effects (Webber and Tuohy, Pediatr Infect Dis J 1987; 7:886); however, Powell (Med J Aust 1988; 15:149) noted that six children developed hemolytic-uremic syndrome following bowel surgery and treatment with metronidazole. No adverse effects were seen in infants who were breast feeding from mothers receiving metronidazole (Passmore, Br J Clin Pharmacol 1988; 26:45).

Toxicity: Metronidazole may cause a deep-brown or reddish discoloration of urine. The drug is well tolerated in adults and apparently also in children. Reported adverse reactions in adults include: nausea, vomiting, diarrhea, erythematous rashes, pruritus, syncope, ataxia, peripheral neuropathy, seizures, reversible neutropenia, reversible thrombocytopenia, and decreased libido. These effects are usually seen only following long-term therapy.

Preparation:
IV: Metronidazole (Flagyl) is a as a proprietary plastic "piggy-back" IV container with 500 mg/100 ml of metronidazole in normal saline (approximately 14 mEq NaCl per 100 ml). An appropriate aliquot should be infused directly from this container. DO NOT REFRIGERATE. PROTECT FROM LIGHT WHEN STORED, though should be stable when exposed to light during infusion (if not direct sunlight).  Do not use if cloudy or if precipitates are present. Do not mix with other additives. Infuse over 1 hour.

PO: A 10 mg/ml suspension of metronidazole (Flagyl) can be prepared by pulverize five 250 mg metronidazole tablets in a mortar. Levigate with a small amount of base solution (base solution is 62.5 ml of Ora-Sweet and 60 ml of Ora-Plus.  Add base solution in increasing amounts while mixing thoroughly. Transfer contents of the mortar to a graduated cylinder. Rinse the mortar and pestle with base solution, pour into graduate. Add basse solution to the graduate to 125 ml.  Transfer to amber glass bottle. Label: shake well and refrigerate. Stable 90 days.

Compatibility: Compatible with TPN and filter as well as with D5W, LR, sterile water for injection, and normal saline.  It is also compatible with acyclovir, allopurinol, amikacin, aminophylline, amiodarone, cefazolin, cefotaxime, ceftazidime, ceftriaxone, cephalothin, chloramphenicol, clindamycin, dysopyramide, esmolol, fluconazole, gentamicin, heparin, hydrocortisone, labetalol, lorazepam, midazolam, morphine, penicillin g (potassium), piperacillin-tazobactam, and tobramycin.  It has equivocal stability with ampicillin and dopamine (no precipitate with "Y-site" administration).  Metronidazole is incompatible with amoxicillin-clavulanate, aztreonam, and meropenem .