One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic–pharmacodynamic (PK–PD) principles to dosing regimens. If antimicrobials are used ...appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK–PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK–PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration.
Antibiotic recommendations for treating skin infections have been published many times in the past 30 years. Prior to 2000, the recommendations focused on the use of β-lactam antibiotics, such as ...cephalosporins, amoxicillin-clavulanate, or β-lactamase stable penicillins. These agents are still recommended, and used, for wild-type methicillin-susceptible strains of Staphylococcus spp. However, since the mid-2000s there has been an increase in methicillin-resistant Staphylococcus spp (MRSP). The increase among S pseudintermedius in animals coincided with the increase in methicillin-resistant S aureus that was observed in people near the same time. This increase led veterinarians to reevaluate their approach to treating skin infections, particularly in dogs. Prior antibiotic exposure and hospitalization are identified as risk factors for MRSP. Topical treatments are more often used to treat these infections. Culture and susceptibility testing is performed more often, especially in refractory cases, to identify MRSP. If resistant strains are identified, veterinarians may have to rely on antibiotics that were previously used uncommonly for skin infections, such as chloramphenicol, aminoglycosides, tetracyclines, and human-label antibiotics such as rifampin and linezolid. These drugs carry risks and uncertainties that must be considered before they are routinely prescribed. This article will discuss these concerns and provide veterinarians guidance on the treatment of these skin infections.
In this review, the availability and deficiencies of current antimicrobial agents for companion animals in the United States are described. Although several active agents are FDA‐approved for small ...animals, there are many unmet needs. These needs are greatest for cats, for the treatment of antibiotic drug‐resistant infections, and to treat new or emerging pathogens that were not considered on older labels. The older agents approved before 1997 are often outdated, unavailable, or have inaccurate labeling. Subsequently, veterinarians treat dogs and cats with many unapproved antimicrobial agents that are licensed for human use. Although these drugs may be effective, there are also concerns that this use can produce drug‐resistant bacteria that may be a public health risk. Although this concern is real, there is also evidence that any antimicrobial use in small animals can produce resistant fecal bacteria and stewardship principles should aim at reducing any unnecessary antibiotic use. This could be accomplished by avoiding some of the older, ineffective, or outdated agents described in this paper. There is a need for incentives to approve new agents that will be more appropriate for treating infections in companion animals without increasing the risk of drug‐resistant bacteria that could potentially be transferred to humans and the environment and create a public health risk.
The Biopharmaceutical Classification System (BCS) has been a prognostic tool for assessing the potential effects of formulation on the human drug oral bioavailability. When used in conjunction with
...in vitro
dissolution tests, the BCS can support the prediction of
in vivo
product performance and the development of mechanistic models that support formulation assessments through the generation of “what if” scenarios. To date, the applicability of existing human BCS criteria has not been evaluated in dogs, thereby limiting its use in canine drug development. Therefore, we examined 50 drugs for which
absolute bioavailability
(
F
) was available both in dogs and humans. The drugs were also evaluated for any potential association between solubility (calculated from the dose number, Do) or lipophilicity (LogP) and
F
in dogs. In humans, solubility is determined in 250 mL of fluid. However, the appropriate volume for classifying drug solubility in dogs has not been established. In this analysis, the estimated volume of a water flush administered to fasted dogs (6 mL) and a volume of 250 mL scaled to a Beagle dog (35 mL) were examined. In addition, in humans, a Do value greater than 1.0 is used to define a compound as
highly soluble
and a LogP value greater than 1.72 as
high permeability
. These same criteria were applied for defining highly soluble and highly permeable in dogs. Whether using 35 or 6 mL to determine Do, the canine solubility classification remained unchanged for all but seven compounds. There were no clear associations between a drug’s
F
in dogs and humans or between the canine value of
F
and either its human BCS classification, its LogP value, or the canine Do estimate. There was a tendency for those drugs with canine values of
F
equal to or greater than 80% to have LogP values equal to or greater than 1.0. Exceptions to this observation tended to be those compounds known to be absorbed via mechanisms other than passive diffusion (e.g., via transporters or paracellular transporters). Although there are limitations to the approach used in this study, the results of our assessment strongly suggest that the human BCS classification system requires substantial modification before it can be reliably applied to dogs.
The objectives of this study were to evaluate a novel kit of resorbable calcium sulfate beads marketed specifically for use in veterinary medicine and generally used for local delivery of ...antimicrobials as carboplatin-delivery system. The study characterized the elution of carboplatin in vitro, and investigated whether the initial dose and formulation of carboplatin, or the bead size significantly influences carboplatin elution in vitro. Calcium sulfate hemihydrate beads of 3- and 5-mm diameter were prepared. Five doses and two formulations of carboplatin (20, 50, 100, and 500 mg carboplatin per kit in powder formulation; 20 mg in liquid formulation) were tested in triplicates for each diameter beads. Beads were placed in 37°C phosphate buffered saline for 72 hours. Carboplatin concentrations in the eluent were measured by high-performance liquid chromatography at 11 time points with a modified United States Pharmacopeia assay. Concentrations of carboplatin in the eluent proportionally increased with the initial dose and peaked between 13 and 52 hours, ranging from 42.1% to 79.3% of the incorporated load. Higher peak concentrations, percentages released, and elution rates were observed with the liquid formulation and with higher carboplatin doses. There was no significant difference in maximum carboplatin concentrations between 3- and 5-mm diameter beads, but 5-mm diameter beads had slower elution rates. The novel kit can be used for preparation of carboplatin-impregnated resorbable calcium sulfate beads at variable doses, sizes and formulations. Further study is warranted to define the in vivo requirements and effective carboplatin dose, spatial diffusion and desired duration of elution.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An update to the 2007 American College of Veterinary Internal Medicine (ACVIM) consensus statement on the identification, evaluation, and management of systemic hypertension in dogs and cats was ...presented at the 2017 ACVIM Forum in National Harbor, MD. The updated consensus statement is presented here. The consensus statement aims to provide guidance on appropriate diagnosis and treatment of hypertension in dogs and cats.
Pharmacokinetics of doxycycline in dogs Papich, Mark G.
Journal of veterinary pharmacology and therapeutics,
20/May , Letnik:
44, Številka:
3
Journal Article
Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food ...animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•These guidelines provide recommendations for the diagnosis and management of bacterial urinary tract infections in dogs and cats.•Sporadic bacterial cystitis, recurrent bacterial cystitis, ...pyelonephritis, bacterial prostatitis, and subclinical bacteriuria are addressed.•Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are discussed.
Urinary tract disease is a common clinical presentation in dogs and cats, and a common reason for antimicrobial prescription. This document is a revision and expansion on the 2011 Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats, providing recommendations for diagnosis and management of sporadic bacterial cystitis, recurrent bacterial cystitis, pyelonephritis, bacterial prostatitis, and subclinical bacteriuria. Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are also addressed.
PDF
