Pilot study of side effects and serum and urine concentrations of amoxicillin–clavulanic acid in azotemic and non-azotemic cats

Abstract

Objectives The aims of this study were to determine the side effect frequency and serum and urine drug concentrations of amoxicillin–lavulanic acid in cats with and without azotemic chronic kidney disease (azCKD). Methods Owners whose cats had been prescribed amoxicillin–clavulanic acid completed a survey regarding the occurrence and type of side effects, and whether treatment was altered as a result. Cats were defined as azCKD (serum creatinine concentration >2.0 mg/dl, urine specific gravity [USG] <1.035 with a clinical diagnosis of CKD) and without azCKD (serum creatinine concentration <2.0 mg/dl). Data were assessed with Fisher’s exact test. Serum and urine samples were obtained from client-owned cats with azCKD (n = 6) and without azCKD (n = 6, serum creatinine concentration <1.8 mg/dl, USG >1.035) that were receiving amoxicillin–clavulanic acid. Amoxicillin and clavulanic acid were measured with liquid chromatography coupled to tandem mass spectrometry and compared between groups with a Mann–Whitney test. Correlation between serum creatinine and drug concentrations in urine and serum was determined using Spearman’s rank test. Results Sixty-one surveys were returned (11 azCKD cats and 50 without azCKD cats). No significant difference in the presence of side effects or type of side effects was seen between groups; however, significantly more azCKD cats had more than one side effect ( P = 0.02). More owners of azCKD cats reported that an alteration in treatment plan was necessitated by side effects (55% vs 12%; P = 0.008). Urine amoxicillin was significantly lower in cats with azCKD ( P = 0.01) and serum amoxicillin trended toward significance ( P = 0.07). Serum amoxicillin concentration was positively correlated with serum creatinine ( P = 0.02; r = 0.62) and urine amoxicillin concentration was negatively correlated with serum creatinine ( P = 0.01; r = –0.65). Conclusions and relevance The data suggest that cats with azCKD have altered pharmacokinetics of amoxicillin, which may contribute to an increased incidence of multiple side effects.

Evaluation of urine concentrations of amoxicillin and clavulanate in cats

“…Cats with decreased urine concentrating ability and azotemia are expected to have lower urine concentrations of antimicrobials, which was confirmed in a recent pilot study including 11 cats with and 50 cats without azotemic chronic kidney disease. 15 In that study, urine was collected by cystocentesis 1 to 2 hours after amoxicillin-clavulanate administration, and the median urine concentration of amoxicillin in cats with azotemic chronic kidney disease was 50.5 μg/mL (range, 8.1-158.5 μg/mL) compared to nonazotemic cats 328.3 μg/mL (range, 33.1-576.5 μg/mL). 15 Therefore, the same urine breakpoints that apply to healthy cats might not apply to cats with renal dysfunction.…”

“…15 In that study, urine was collected by cystocentesis 1 to 2 hours after amoxicillin-clavulanate administration, and the median urine concentration of amoxicillin in cats with azotemic chronic kidney disease was 50.5 μg/mL (range, 8.1-158.5 μg/mL) compared to nonazotemic cats 328.3 μg/mL (range, 33.1-576.5 μg/mL). 15 Therefore, the same urine breakpoints that apply to healthy cats might not apply to cats with renal dysfunction.…”

“…Once recovered from sedation, the cats were returned to university animal housing, and efforts were made to adopt them. 15 Therefore, the same urine breakpoints that apply to healthy cats might not apply to cats with renal dysfunction.…”

Drug-Dosing Adjustment in Dogs and Cats with Chronic Kidney Disease

“…Due to the possible accumulation, dose adjustment could be considered for ampicillin in dogs with severe azotemia [61]. Although penicillins have been classified as "probably safe" in cats with CKD [7,13], the need for dose adjustment in azotemic feline patients remains to be determined [62].…”

“…The dose adjustment of penicillin in cats with impaired renal function appears to be unnecessary due to the wide therapeutic window of these antimicrobials, which could be classified as "probably safe" in CKD patients [7,13]. The side effects of amoxicillinclavulanic acid were evaluated in feline patients with and without azotemic CKD, with altered pharmacokinetics observed in cats with azotemic CKD; however, the need for dose adjustments in azotemic feline patients remains to be determined [62].…”