Use of tissue–fluid correlations to estimate gentamicin residues in kidney tissue of Holstein steers

Abstract

Gentamicin continues to be one of the most effective antibiotics for the treatment of gram-negative infections. Greater than 90% of the drug is rapidly eliminated from the body in <2 days, however, a small residue remains bound to the kidney cortex tissue for many months. In beef steers, the gentamicin residue is unacceptable and its presence is monitored by the FAST (Fast Antimicrobial Screen Test) applied to the kidney at the time of slaughter. The sensitivity of the FAST to gentamicin in the kidney cortex is reported to be 100 ng/g, therefore, this level of gentamicin defines the acceptable limit of gentamicin drug residue in the bovine kidney. In the present study, three doses of 4 mg/kg gentamicin was administered intramuscularly to eight steers. Gentamicin was allowed to deplete from the kidneys for a range of times from 7 to 10 months. At slaughter the level of gentamicin in the kidney cortex varied from 91 to 193 ng/g, but a total of 160 FAST tests performed on the kidneys were negative. Blood and urine samples were collected at varying times following the last dose of gentamicin. Kidney tissue samples were collected by laparoscopic surgery in the live steers as well as the final sample obtained at slaughter. Plasma levels of gentamicin declined rapidly to nondetectable within 3 days, while measurable urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique. An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggests a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL will correlate with the estimated 100 ng/g gentamicin limit of the FAST applied to the fresh kidney of the recently slaughtered bovine.

Comparison of three microbial screening methods for antibiotics using routine monitoring samples

“…Aminoglycosides are specifically bound in the renal cortex and released from this tissue only very slowly, causing detectable residue levels for months after treatment [20,21]. The NAT-screening showed nine suspect samples on the aminoglycoside test plate, which were also positive on the post-screening kidney.…”

Detection of penicillin residues in bovine oral fluid (saliva) by liquid chromatography/tandem mass spectrometry

“…2 A novel laparoscopic surgical technique was used to obtain kidney cortex samples from standing animals. 3 In the course of those studies, we also obtained a few samples of oral fluid from steers that had been dosed with penicillin. (Saliva refers to fluid secreted by the salivary gland.…”

Toxicokinetics and Organ-Specific Toxicity

“…An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggested a urine to kidney tissue relationship of 1:100. A test system sufficiently sensitive to a urine gentamicin concentration of 1 ng/mL correlated with the estimated 100 ng/g gentamicin limit applied to the fresh kidney of the recently slaughtered bovine (Chiesa et al, 2006). This example highlights the utility of measuring excreta (e.g., urine) to better estimate concentrations of drug in tissue (e.g., kidney).…”

“…For example in beef steers treated with gentamicin, a small residue remains bound to the kidney cortex tissue for many months (this residue is unacceptable at the time of slaughter). Interestingly, plasma levels of gentamicin declined rapidly to no detectable levels within 3 days after intramuscular administration of gentamicin, while measurable amounts in urine persisted for 75 days before the concentration of gentamicin declined to levels too low to quantitate by the available liquid chromatography tandem mass spectrometry (LC/MS/MS) technique (Chiesa et al, 2006). An estimated correlation between an extrapolation of urine gentamicin concentration to the corresponding kidney tissue sample suggested a urine to kidney tissue relationship of 1:100.…”