Relative Oral Bioavailability of Two Amoxicillin–Clavulanic Acid Formulations in Healthy Dogs: A Pilot Study

2019 ◽  
Vol 55 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Jennifer Moczarnik ◽  
Darren J. Berger ◽  
James O. Noxon ◽  
Dana N. LeVine ◽  
Zhoumeng Lin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Clavulanic Acid ◽  
Coefficient Of Variation ◽  
Oral Bioavailability ◽  
Drug Exposure ◽  
Comparative Investigation ◽  
Pharmacokinetic Parameters ◽  
Pilot Investigation ◽  
Amoxicillin Clavulanic Acid ◽  
Healthy Dogs

ABSTRACT The use of human generic amoxicillin–clavulanic acid formulations in veterinary medicine is currently lacking supportive evidence. This pilot study was conducted to determine preliminary pharmacokinetic parameters and relative oral bioavailability of a human generic and veterinary proprietary 4:1 amoxicillin–clavulanic acid formulation in healthy dogs to evaluate whether drug exposure was similar and to determine if further comparative investigation is warranted. Each dog received a single oral dose of each formulation containing 500:125 mg of amoxicillin–clavulanic acid at two separate instances with a 2 wk washout period between product administration. Following drug administration, blood was collected at fixed times over 24 hr to measure plasma amoxicillin and clavulanic acid concentrations using liquid chromatography–mass spectrometry. There were no statistically significant differences between pharmacokinetic parameters of either formulation. Clavulanic acid showed greater between-dog variation in drug exposure between formulations compared with amoxicillin and was also observed to be more variable within the veterinary proprietary formulation. The average relative oral bioavailability was 98.2% (23.6% coefficient of variation) for amoxicillin and 152.6% (64.3% coefficient of variation) for clavulanic acid between formulations. This pilot investigation supports the need for further bioequivalence studies regarding these formulations before commenting on product interchangeability.

scholarly journals Population Pharmacokinetics of Intravenous Amoxicillin Combined With Clavulanic Acid in Healthy and Critically Ill Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Maria D. Vegas Cómitre ◽  
Stefano Cortellini ◽  
Marc Cherlet ◽  
Mathias Devreese ◽  
Beatrice B. Roques ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Clavulanic Acid ◽  
Critically Ill ◽  
Drug Exposure ◽  
De Novo ◽  
Clinical Failure ◽  
Clinical Covariates ◽  
Amoxicillin Clavulanic Acid ◽  
Healthy Dogs

Background: Data regarding antimicrobial pharmacokinetics (PK) in critically ill dogs are lacking and likely differ from those of healthy dogs. The aim of this work is to describe a population PK model for intravenous (IV) amoxicillin–clavulanic acid (AMC) in both healthy and sick dogs and to simulate a range of clinical dosing scenarios to compute PK/PD cutoffs for both populations.Methods: This study used a prospective clinical trial in normal and critically ill dogs. Twelve client-owned dogs hospitalized in the intensive care unit (ICU) received IV AMC 20 mg/kg every 8 h (0.5-h infusion) during at least 48 h. Eight blood samples were collected at predetermined times, including four trough samples before the next administration. Clinical covariates and outcome were recorded, including survival to discharge and bacteriologic clinical failure. Satellite PK data were obtained de novo from a group of 12 healthy research dogs that were dosed with a single AMC 20 mg/kg IV. Non-linear mixed-effects model was used to estimate the PK parameters (and the effect of health upon them) together with variability within and between subjects. Monte Carlo simulations were performed with seven dosage regimens (standard and increased doses). The correlation between model-derived drug exposure and clinical covariates was tested with Spearman's non-parametric correlation analysis. Outcome was recorded including survival to discharge and bacteriologic clinical failure.Results: A total of 218 amoxicillin concentrations in plasma were available for healthy and sick dogs. A tricompartmental model best described the data. Amoxicillin clearance was reduced by 56% in sick dogs (0.147 L/kg/h) compared with healthy dogs (0.336 L/kg/h); intercompartmental clearance was also decreased (p <0.01). None of the clinical data covariates were significantly correlated with individual exposure. Monte Carlo simulations showed that higher PK/PD cutoff values of 8 mg/L could be reached in sick dogs by extending the infusion to 3 h or doubling the dose.Conclusions: The PK of AMC is profoundly different in critically ill dogs compared with normal dogs, with much higher interindividual variability and a lower systemic clearance. Our study allows to generate hypotheses with regard to higher AMC exposure in clinical dogs and provides supporting data to revise current AMC clinical breakpoint for IV administration.

scholarly journals Susceptibility of Incisional Site Staphylococcus spp. to Three Common Perioperative Antimicrobials in Dogs Undergoing Clean Orthopaedic Procedures

VCOT Open ◽  
2020 ◽  
Vol 03 (02) ◽  
pp. e158-e163
Author(s):  
Po-Yen Chou ◽  
Duane Robinson ◽  
Amy S. Kapatkin ◽  
Steven E. Epstein ◽  
Michelle A. Giuffrida ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Prospective Observational Study ◽  
Bacterial Isolates ◽  
Susceptibility Pattern ◽  
Coagulase Negative Staphylococci ◽  
Bacillus Spp ◽  
Amoxicillin Clavulanic Acid ◽  
Healthy Dogs ◽  
Staphylococcus Spp ◽  
Coagulase Positive Staphylococci

Abstract Objectives The aim of this study was to evaluate the susceptibility pattern of the incisional site Staphylococcus spp. to three commonly used perioperative antimicrobials in dogs. Materials and Methods A cohort of client-owned dogs was included in this prospective observational study. After induction of general anaesthesia and hair clipping, culture samples were collected from the incisional site of healthy dogs before orthopaedic surgery. The isolated colonies were identified. The susceptibility pattern of staphylococcal isolates was determined using Clinical and Laboratory Standard Institute standards. The staphylococcal susceptibilities to amoxicillin/clavulanic acid and cefpodoxime were compared with cefazolin using two-sided equality of proportions test. Results A total of 391 bacterial isolates were identified in 115 dogs. Bacillus spp. (n = 200) and Staphylococcus spp. (n = 95) were the most common bacteria isolated. Coagulase- positive and -negative staphylococci were isolated in 44 and 38% of dogs respectively. Cefazolin, amoxicillin/clavulanic acid and cefpodoxime staphylococcal susceptibilities were 68, 77 and 76% respectively. There were no significant differences in Staphylococcus spp. susceptibility between amoxicillin/clavulanic acid or cefpodoxime and cefazolin (p = 0.19, p = 0.25). Thirty-six per cent of coagulase-negative staphylococci and 6% of coagulase-positive staphylococci isolated were methicillin resistant. Conclusion Cefazolin, amoxicillin/clavulanic acid and cefpodoxime had similar susceptibilities for staphylococcal isolates. Routine use of amoxicillin/clavulanic acid or cefpodoxime in replace of cefazolin should be practiced with caution.

scholarly journals Substandard Quality of the Antimicrobials Sold in the Street Markets in Haiti

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 407
Author(s):  
Théodule Jean-Baptiste ◽  
John F. Carpenter ◽  
Kevin Dahl ◽  
Wellington Derameau ◽  
Rosemela Veillard ◽  
...  
Keyword(s):  
Pilot Study ◽  
Field Study ◽  
Clavulanic Acid ◽  
Amoxicillin Clavulanic Acid ◽  
Spectral Match

This pilot study was conducted to analyze the quality of the antimicrobials sold in the street markets in Port-au-Prince, Haiti. A total of 258 packs containing antimicrobials were bought in 28 street markets in Port-au-Prince (Haiti). Tablets and contents of capsules included in 196 packs were analyzed using a Raman handheld spectrometer (NanoRAM of BWTEK, Model: BWS456-785) during the first quarter of 2019. Three out of 11 antimicrobials (Amoxicillin, Metronidazole, and Cotrimoxazole) had a high spectral match with an HQI ≥ 90 to the respective authentic medicine for more than 95% of their tablets/capsules. For six antimicrobials (Tetracycline, Erythromycin, Cloxacillin, Azithromycin, Clarithromycin, and the combination Amoxicillin + Clavulanic Acid) none of their tablets/capsules showed a sufficient spectral match with the authentic medicine. This finding indicates that these products sold in the markets did not contain the labeled drug and/or contained a degraded drug. In addition to the fact that prescription antimicrobials can be purchased in street markets, the present field study found that for most of them (including “Watch” antimicrobials according to the AWaRe classification) were substandard, which contributes to the present antimicrobials resistance epidemic.

Is perioperative antibiotic necessary in straightforward implant placement procedures?

2020 ◽  
Author(s):  
Elçin Bedeloğlu ◽  
Mustafa Yalçın ◽  
Cenker Zeki Koyuncuoğlu
Keyword(s):  
Clavulanic Acid ◽  
Dental Implant ◽  
Prophylactic Antibiotic ◽  
Antibiotic Use ◽  
Implant Failure ◽  
Control Group ◽  
Implant Placement ◽  
Significant Difference ◽  
Amoxicillin Clavulanic Acid ◽  
Experimental Group

The purpose of this non-random retrospective cohort study was to evaluate the impact of prophylactic antibiotic on early outcomes including postoperative pain, swelling, bleeding and cyanosis in patients undergoing dental implant placement before prosthetic loading. Seventy-five patients (45 males, 30 females) whose dental implant placement were completed, included to the study. Patients used prophylactic antibiotics were defined as the experimental group and those who did not, were defined as the control group. The experimental group received 2 g amoxicillin + clavulanic acid 1 h preoperatively and 1 g amoxicillin + clavulanic acid twice a day for 5 days postoperatively while the control group had received no prophylactic antibiotic therapy perioperatively. Data on pain, swelling, bleeding, cyanosis, flap dehiscence, suppuration and implant failure were analyzed on postoperative days 2, 7, and 14 and week 12. No statistically significant difference was detected between the two groups with regard to pain and swelling on postoperative days 2, 7, and 14 and week 12 ( p >0.05), while the severity of pain and swelling were greater on day 2 compared to day 7 and 14 and week 12 in both groups ( p =0.001 and p <0.05, respectively). Similarly, no significant difference was found between the two groups with regard to postoperative bleeding and cyanosis. Although flap dehiscence was more severe on day 7 in the experimental group, no significant difference was found between the two groups with regard to the percentage of flap dehiscence assessed at other time points. Within limitations of the study, it has been demonstrated that antibiotic use has no effect on implant failure rates in dental implant surgery with a limited number of implants. We conclude that perioperative antibiotic use may not be required in straightforward implant placement procedures. Further randomized control clinical studies with higher numbers of patients and implants are needed to substantiate our findings.

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