Kazuki Harada

Background/Objectives: Piperacillin–tazobactam (TZP) is a potential alternative to carbapenems for the treatment of dogs infected with extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), but its efficacy remains unestablished. In this study, pharmacokinetic–pharmacodynamic (PK/PD) analysis was performed to estimate the clinical efficacy of TZP against ESBL-E infections in dogs. Methods: We determined the minimum inhibitory concentrations (MICs) of TZP in canine ESBL-E isolates, including Escherichia coli (n = 62), Klebsiella pneumoniae (n = 89), and Enterobacter cloacae (n = 31), using agar dilution. Monte Carlo Simulation (MCS) was performed to estimate the probability of target attainment (PTA) based on the PK/PD characteristics of TZP. Results: The MICs that can inhibit the growth of 90% of the isolates for the three bacterial species were determined as 16/4 µg/mL. MCS analysis revealed that the piperacillin PK/PD cutoff values (highest MICs with a PTA ≥90%) were ≤0.031, ≤0.5, and ≤2 μg/mL at a bolus dose of 50 mg/kg TZP (44.4 mg/kg piperacillin) every 12, 8, and 6 h (q12h, q8h, and q6h), respectively. The cumulative fractions of response were ≤90% based on the MIC distribution of ESBL-producing E. coli, K. pneumoniae, and E. cloacae isolates from dogs: 1.60, 0.48, and 0.15% at q12h; 32.56, 14.57, and 9.65% at q8h; and 74.51, 45.85, and 43.92% at q6h, respectively. Conclusions: We believe that TZP is not recommended for the treatment of canine ESBL-E infections, except for cases with a lower MIC than the PK/PD cutoff values determined in this study.

A 13-year-old female Persian cat with a heart murmur presented with dyspnea. Thoracic radiography revealed pleural effusion and dilation of peripheral pulmonary vessels. Echocardiography showed significant enlargement of the right atrium and ventricle and left atrial appendage; an atrial septal defect (ASD) near the atrioventricular valves; and a septum-like structure below the left atrial appendage. Left-to-right shunting through the ASD was noted, with a pulmonary-to-systemic flow ratio of 2.72. The cat was diagnosed with incomplete atrioventricular septal defect (IAVSD) and supravalvular mitral stenosis (SVMS) and subsequently medically managed for 7 months before death. Necropsy confirmed IAVSD with a mitral valve cleft and SVMS. To our knowledge, this is the longest reported survival in a cat with both anomalies.

5-Aminolevulinic acid is a lipid metabolism-promoting functional amino acid. This study investigated the effect of 5-aminolevulinic acid on hypercholesterolemia in Shetland Sheepdogs. Ten Shetland Sheepdogs with (H group; n = 7) and without hypercholesterolemia (C group; n = 3) were enrolled. All the dogs were orally administered once a day with a supplement containing 5-aminolevulinic acid at a dose of 5 mg (body weight < 10 kg) or 10 mg (body weight ≥ 10 kg). Fasting blood tests, including cholesterol and the related lipoproteins, were evaluated at four time points: at the beginning of the study (baseline) and at 1, 2, and 3 months thereafter. In the H group, total cholesterol decreased from 424.7 ± 19.9 mg/dL (baseline) to 371.2 ± 19.7, 361.4 ± 16.8, and 355.0 ± 18.0 mg/dL at 1, 2, and 3 months (p < .05). Low-density lipoprotein cholesterol also declined from 195.0 ± 16.6 mg/dL to 137.7 ± 12.7, 123.4 ± 11.7, and 117.9 ± 11.9 mg/dL at 1, 2, and 3 months (p < .05). However, no significant fluctuations were observed in the blood test results of the C group. The present findings indicate that 5-aminolevulinic acid supplementation is a potential therapeutic option for hypercholesterolemia in Shetland Sheepdogs.Cite this article as: Sakai, A., & Harada, K. (2025). Open-label pilot clinical trial on the effect of 5-aminolevulinic acid on hypercholesterolemia in shetland sheepdogs. Acta Veterinaria Eurasia, 51, 0028, doi: 10.5152/actavet.2025.25028.

We investigated the distribution and antimicrobial resistance of 120 Staphylococcus felis isolates from feline patients in Japan, mainly from the urinary tract (28.3%), abscesses (23.3%), ears (22.5%), and nasal cavity (10.8%). The distribution of S. felis differed from those of previous studies in Japan and other countries. Antimicrobial susceptibility testing revealed a relatively high resistance to penicillin (PEN, 33.3%), followed by erythromycin (ERY, 15.8%), clindamycin (CLI, 13.3%), and levofloxacin (5.0%). However, oxacillin resistance was not detected. Notably, 11/120 (9.2%) S. felis isolates exhibited multidrug resistance, i.e., resistance to more than three classes of drugs, which mainly consisted of PEN-ERY-CLI resistance phenotypes. This is the first investigation on antimicrobial-resistant S. felis isolates from feline patients in Japan.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales-producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs using a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs were intravenously administered at a bolus dose of FMX (40 mg/kg body weight). Serum concentrations of FMX were calculated with high-performance liquid chromatography-tandem mass spectrometry, and then applied to determine PK indices based on a non-compartmental model. The cumulative fraction of response (CFR) was estimated based on the dissemination of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. From the results, the dosage regimens of 40 mg/kg every 6 and 8 h were estimated to attain a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. By contrast, all regimens had a CFR of Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX every 6 and 8 h can be a non-carbapenem treatment for canine infections of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those of ESBL-producing Enterobacter cloacae.

One of the most significant research areas in veterinary medicine is the search for carbapenem substitutes for the treatment of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E). This study applied a pharmacokinetic/pharmacodynamic (PK/PD) strategy in validating optimal latamoxef (LMX) therapeutic regimens against canine ESBL-E infections. Five dogs were administered a bolus dose of 40 mg/kg LMX intravenously to measure serum drug concentrations and determine PK indices using the noncompartmental model. The highest minimum inhibitory concentration (MIC) with a probability of target attainment ≥90% was used to compute the PK/PD cutoff values for bacteriostatic (time for which the unbound drug concentration was above the MIC [fTAM] ≥40%) and bactericidal (fTAM ≥70%) effects when administered at 20, 30, 50, and 60 mg/kg, in addition to 40 mg/kg. The cumulative fraction of response (CFR) was determined using the MIC distribution of wild-type ESBL-E in companion animals. The PK/PD cutoff values can be increased by reducing the dosing interval rather than increasing the dose per time. Based on the calculated CFRs for ESBL-producing Escherichia coli and Klebsiella pneumoniae, all LMX regimens in this study and those administered at 30–60 mg/kg every 8 and 6 hr were found to be optimal (CFR ≥90%) for exerting bacteriostatic and bactericidal effects, respectively. However, the regimens of 50 and 60 mg/kg every 6 hr may merely exert bacteriostatic effects on ESBL-producing Enterobacter cloacae. Further clinical trials are required to confirm the clinical efficacy of LMX.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

Introduction: The spread of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is a serious concern in companion animal medicine owing to their ability to develop multidrug resistance. Cefmetazole (CMZ) is a candidate drug for treating ESBL-E infections; however, its regimen in dogs has not been established. In this study, we investigated the pharmacokinetic (PK) indices of CMZ in dogs and performed PK–pharmacodynamic (PD) analyses using Monte Carlo Simulation (MCS).Methods: In total, six healthy dogs received an intravenous bolus dose of CMZ (40 mg/kg body weight). Serum CMZ concentrations were evaluated using liquid chromatography–mass spectrometry, and PK indices were determined based on non-compartmental analysis. The PK–PD cut-off (COPD) values were calculated as the highest minimum inhibitory concentration (MIC) that achieved ≥90% probability of target attainment for a target value of unbounded drug concentration exceeding 40% of the dosing interval. The cumulative fraction of response (CFR) was calculated based on the MIC distribution of wild-type ESBL-E from companion animals.Results: The area under the concentration–time curve and elimination half-time were 103.36 ± 7.49 mg·h/L and 0.84 ± 0.07 h, respectively. MCS analysis revealed that COPD values for regimens of 40 mg/kg q12, q8h, and q6h were ≤ 0.5, ≤2, and ≤ 4 μg/mL, respectively. A regimen of 40 mg/kg q6h was estimated to achieve a CFR of 80–90% for Escherichia coli and Klebsiella pneumoniae. By contrast, all regimens exhibited a CFR of ≤70% for Proteus mirabilis and Enterobacter cloacae.Discussion: We conclude that CMZ at 40 mg/kg q6h could be a viable treatment regimen for dogs infected with ESBL-producing Escherichia coli and Klebsiella pneumoniae.