Once daily dosing of aminoglycosides has been suggested as an alternative method for delivering therapeutic drug levels to patients. Multiple case studies in humans have yielded results which indicate single daily dosing has comparable therapeutic efficacy to BID dosing, while decreasing risk of toxicity. The effectiveness of aminoglycoside when administered as once daily dosing is believed to be related to three factors: 1) concentration dependent bactericidal activity; 2) Increased post antibiotic effect (PAE) with higher initial serum concentrations. PAE is defined as the period of bacterial growth suppression after the cessation of bacterial exposure to the particular antibiotic; and 3) A rapid attainment of high serum antibiotic concentration. Rapid attainment of serum concentrations has been correlated to increased survival rates in patients with gram negative infection. In humans, dosages range from 11.0 to 35.0 mg/kg SID, with peak and trough blood levels ranging from 33 to 57.8 mg/l and less than 2.0 mg/l, respectively.

Sea World of Texas used single daily amikacin dosing in two beluga whales and an Asian small-clawed otter. Case 1 was a 1000 kg, 18 yr. old male beluga whale with a 22 month history of reoccurring subcutaneous nocardiosis. After multiple treatment attempts, he was placed on BID amikacin (Amiglyde-V, Fort Dodge Lab., INC., Fort Dodge, Iowa 50501, USA) at 7.7 mg/kg IM and azithromycin (6.8 mg/kg; Zithromax, Pfizer Labs., New York, New York 10017, USA) PO SID for 31 days. Since reported treatment of nocardiosis in humans requires a minimum of six months antibiotic exposure.

(B. Beaman, personal communication -Sept. 1995, Dept. Medical Microbiology and Immunology, UC Davis, Davis, CA 95616,), it was decided to use single amikacin dosing to minimize injection trauma and reduce daily handling. Thus, the animal was changed to a single daily dose of amikacin at 16.4 mg/kg for 52 days. Serum concentrations at 0 hr. 30 min., 1, 2, 6, 12, and 24 hr were 2.0, 52.6, 77.7, 58.8, 12.4, 2.4, and 1.0 ug/ml, respectively (Figure 1). Due to clinical signs of lethargy and unresponsiveness, and an elevated BUN and creatinine his dose of amikacin was changed to 11.6 mg/kg IM SID and treatment continued for an additional 68 days. Therefore, this animal received amikacin BID for 31 days and SID for 120 days resulting in a total treatment time of 151 days without any lasting untoward effects on hematology or chemistries. Case 2 involved a 249 kg, 2 yr. old male beluga whale with an acute infectious process characterized by a degenerative left shift. He was placed on a combination of amikacin 15.6 mg/kg IM SID and amoxicillin/clavulanic acid (22 mg/kg; Augmentin, SmithKline Beecham, Philadelphia, PA 19101, USA) PO BID. One hour peak and 24 hr trough levels of amikacin were 52.0 and 2.6 ug/ml, respectively. Trough levels repeated 17 days later were < l .0 ug/ml. He was maintained on the combination for 35 days. Case 3 involved a 3.6 kg, 7 yr. old male Asian small-clawed otter with a history of reoccurring inappetence and weight loss, most likely due to chronic infection based on hematology and chemistries. He had previously been treated for 19 days with amikacin (10 mg/kg) IM BID. His clinical response was good, however, he relapsed 41 days after treatment was discontinued. Amikacin was again given, this time at 22 mg/kg IM SID. The 12 min., 30 min. and 24 hr serum amikacin concentrations were 34.8, 32.9 and <1.0 ug/ml, respectively. Treatment was discontinued after 37 days. His weight has returned to 3.9 kg and he remains behaviorally and clinically normal. Once daily amikacin administration has allowed for both reduced animal handling, and injection trauma while maintaining the clinical efficacy of the drug.

This is a Sea World of Texas technical contribution no. 9601-T.

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