Plasma and Urine Pharmacokinetics of Oral Fosfomycin Tromethamine in Dogs

Jariyapamornkoon, Nattha; Patthanachai, Koranis; Suanpairintr, Nipattra

doi:10.3390/vetsci10060391

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…The plasma pharmacokinetics of florfenicol in dogs have been described, but florfenicol is not used clinically as an oral medication for systemic infections in dogs because of its short plasma half-life and low plasma concentrations (Park et al, 2009). However, other drugs with short plasma half-life and low plasma concentrations, such as nitrofurantoin and fosfomycin, reach high urinary concentrations (Hung et al, 2023;Jariyapamornkoon et al, 2023;Leuin et al, 2021). If florfenicol is excreted in sufficient concentrations in the urine of dogs, then it could be effective for UTI independent of plasma drug concentrations.…”

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confidence: 99%

Florfenicol urinary excretion and its potential for treating canine urinary tract infections

KuKanich,

Anderson,

Carcamo Tzic

et al. 2024

Vet Pharm & Therapeutics

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The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose‐bred Beagles and four healthy client‐owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client‐owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23–3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half‐life was similar for the Beagles and the Pug, 0.75–1.39 h, whereas the half‐life was 1.70–1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild‐type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6‐12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple‐dose regimens) before considering clinical trials or breed‐specific differences.

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Section: Introductionmentioning

confidence: 99%

Florfenicol urinary excretion and its potential for treating canine urinary tract infections

KuKanich,

Anderson,

Carcamo Tzic

et al. 2024

Vet Pharm & Therapeutics

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Antibiotic efficacy and resistance patterns of urinary tract infection-causing bacteria in dogs and resistome of multidrug-resistant Klebsiella pneumoniae via whole genome sequencing in South Korea

Lee,

Hyeon,

Kang

et al. 2024

Front. Vet. Sci.

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Bacterial urinary tract infections (UTIs) are prevalent in dogs and necessitate antibiotic intervention. However, the emergence of multidrug-resistant (MDR) bacteria poses significant challenges to antibiotic therapy. Although fosfomycin has been demonstrated to achieve and maintain high concentrations in urine, suggesting its potential for treating UTIs in dogs, its efficacy and the resistance profiles of urinary pathogens from canine UTIs remain elusive. Therefore, this study was conducted to investigate the antibiotic susceptibility of bacterial pathogens isolated from companion dogs with UTIs, with a particular focus on their susceptibility and resistance to fosfomycin. A total of 70 isolates from urine samples were analyzed, of which Escherichia coli (n = 18), Proteus mirabilis (n = 9), Klebsiella pneumoniae (n = 5), and Staphylococcus pseudintermedius (n = 5) were predominant. Resistance to erythromycin was most prevalent (94.59%), followed by clindamycin (91.89%) and ampicillin (78.37%), whereas the lowest resistance rate was observed for amikacin (5.40%). Resistance to fosfomycin was observed in 15 out of the 37 predominant isolates (40.54%), including all K. pneumoniae isolates (100%). All isolates, except 4 E. coli strains, were categorized as MDR (33 out of 37; 89.18%). The resistance rates for amoxicillin/clavulanic acid and trimethoprim-sulfamethoxazole, which are common first-line antibiotics for canine UTIs, were 48.64 and 56.75%, respectively. Whole-genome sequencing of K. pneumoniae isolates, which exhibited high resistance to fosfomycin, revealed multiple antibiotic resistance genes, with chromosomal fosA present in all isolates. Among the 27 dogs with recurrent infection included in this study, 2 were administered fosfomycin, resulting in clinical remission, as evidenced by negative urine culture tests. Overall, this study is the first to demonstrate the importance of assessing fosfomycin resistance profile for optimal treatment of canine UTIs, particularly in cases involving MDR strains.

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In Vitro Antibacterial Activities of Fosfomycin against Escherichia coli Isolates from Canine Urinary Tract Infection

Jariyapamornkoon,

Nuanualsuwan,

Suanpairintr

2024

Animals

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Fosfomycin is a bactericidal drug recommended as an alternative treatment for canine bacterial cystitis, particularly in cases involving multidrug-resistant (MDR) infections when no other options are available. In this study, minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of fosfomycin were determined against 79 clinical E. coli isolates using the agar dilution method. The susceptibility rate of E. coli to fosfomycin was 86.06%, with MIC50 and MIC90 values of 4 mg/L and 96 mg/L, respectively. MPC50 and MPC90 values were 64 mg/L and 192 mg/L. Using pharmacokinetic (PK) data from dogs given a single 80 mg/kg oral dose of fosfomycin, the area under the curve per MIC50 (AUC0–24/MIC50) was 85.79 with time above MIC50 (T > MIC50) exceeding 50%. In urine, the AUC0–24/MIC50 was 10,694.78, and the AUC0–24/MPC90 was 222.81, with T > MPC90 extending beyond 24 h. Therefore, fosfomycin exhibited significant antibacterial activity against canine uropathogenic E. coli, including MDR strains, at concentrations below the susceptible MIC breakpoint. However, the high MPC values, especially the MPC90, indicate the critical importance of performing susceptibility testing for fosfomycin and maintaining ongoing resistance monitoring.

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Plasma and Urine Pharmacokinetics of Oral Fosfomycin Tromethamine in Dogs

Cited by 3 publications

References 37 publications

Florfenicol urinary excretion and its potential for treating canine urinary tract infections

Florfenicol urinary excretion and its potential for treating canine urinary tract infections

Antibiotic efficacy and resistance patterns of urinary tract infection-causing bacteria in dogs and resistome of multidrug-resistant Klebsiella pneumoniae via whole genome sequencing in South Korea

In Vitro Antibacterial Activities of Fosfomycin against Escherichia coli Isolates from Canine Urinary Tract Infection

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