Dose:   100 mg/kg/ as loading dose IV, IM
               75 mg/kg/dose maintenance

Frequency: Q 12 hour if < 1 week and < 2000 grams
                      Q 8 hour if > 1 week and > 2000 grams     
                      Q 6 hour if > 1 month
                      Q 8 hour for LBW infants until > 28 weeks PCA
                       Adjust dose with renal and hepatic dysfunction.

Comments: Ticarcillin/clavulanate is a combination of ticarcillin, a ureidopenicillin antibiotic, and clavulanate, a beta-lactamase inhibitor. It may be particularly useful in treating infections caused by Pseudomonas. It may also be useful in treating ampicillin resistant and beta-lactamase producing strains of Klebsiella, E. coli, Proteus, Acinetobacter, Bacteroides, Clostridia, and H. influenza. Most Enterobacter are resistant. Results in treating bacteremia caused by Staph. epidermidis or most other gram positive pathogens are suboptimal.  IV peak levels are four times greater than seen following IM administration.  At present, there are no specific recommendations for use of this drug in the newborn. Much of the information is based upon that of ticarcillin, which is no longer carried by the pharmacy. At the present time although the drug is safe, it use should be restricted to situations treating multiply-resistant bacteria when other antimicrobials have failed. Bacterial resistance has developed to ticarcillin in vitro when suboptimal doses were used. Further comments on ticarcillin/clavulanate.

Toxicity: Timentin is capable of producing all of the side effects seen with penicillin (adverse reactions with penicillin).   The following have been reported in adults but it is not known if similar problems with be seen in the newborn. Hypernatremia and heart failure can occur due to the sodium contained in the preparation (4.75 mEq/gram of ticarcillin). Hypokalemia can occur due to the large losses of ticarcillin in the distal tubule as non-reabsorbable anion. Bleeding may develop secondary to abnormal platelet aggregation. This is a dose-related phenomenon. The presence of ticarcillin in the urine will cause a false positive test for protein unless measured by Multi-stix reagent strip. The clavulanate can cause a nonspecific binding of IgG to red cells producing a positive Coombs test. 

Preparation: Ticarcillin/clavulanate (Timentin) is available in a 3.1 gram vial (3 grams of ticarcillin and 0.1 gram of clavulanic acid).   Doses are based on the content of ticarcillin.  It is reconstituted by adding 13 ml of sterile water to produce a ticarcillin concentration of 200 mg/ml. This is further diluted to a 50 mg/ml concentration with the addition of 6 ml of D5W to 2 ml of the concentrated solution. The 50 mg/ml reconstituted vial stable for 24 hours if refrigerated. Infuse over 30 minutes.

Compatibility: Compatible with TPN and presumably with filter.  Also  compatible with sterile water for injection, D5W, LR, normal saline, allopurinol, aztreonam, famotidine, filgrastim, fluconazole, heparin, insulin, morphine, and propofol.  Incompatible with amikacin, gentamicin, kanamycin, and tobramycin due to inactivation of the aminoglycosides by ticarcillin.