Antimicrobial susceptibility patterns of clinical Escherichia coli isolates from dogs and cats in the United States: January 2008 through January 2013.

Escherichia coli is among the most common bacterial pathogens in dogs and cats. The lack of a national monitoring program limits evidence-based empirical antimicrobial choices in the United States. This study describes antimicrobial susceptibility patterns for presumed clinical E. coli isolates from dogs (n=2392) or cats (n=780) collected from six geographic regions in the United States between May 2008 and January 2013. Minimum inhibitory concentrations (MIC) were determined for 17 drugs representing 6 drug classes. Urinary tract isolates were most common (71%). Population MIC distributions were generally bimodal with the second mode above the resistant breakpoint for all drugs except gentamicin, amikacin, and meropenem. The MIC90 exceeded the susceptible breakpoint for ampicillin, amoxicillin-clavulanic acid, cephalothin (surrogate drug for cephalexin), and doxycycline but was below the susceptible breakpoint for all others. None of isolates was susceptible or resistant to all drug tested; 46% were resistant to 1 or 2 antimicrobial categories, and 52% to more than three categories. The resistance percentages were as follows: doxycycline (100%), cephalothin (98%)>ampicillin (48%)>amoxicillin-clavulanic acid (40%)>ticarcillin-clavulanic acid (18%)>cefpodoxime (13%), cefotaxime (12%), cefoxitin (11%), cefazolin (11%), enrofloxacin (10%), chloramphenicol (9.6%)>ciprofloxacin (9.2%), ceftazidime (8.7%), trimethoprim-sulfamethoxazole (7.9%), gentamicin (7.9%)>meropenem (1.5%), amikacin (0.7%) (P<0.05). Resistance to ampicillin and amoxicillin-clavulanic acid was greatest in the South-Central region (P<0.05). E. coli resistance may preclude empirical treatment with doxycycline, cephalexin, ampicillin, or amoxicillin-clavulanic acid. Based on susceptibility patterns, trimethoprim-sulfonamides may be the preferred empirical oral treatment.

Antimicrobial considerations in the perioperative patient.

Surgical site infections are among the complications that can be reduced with the timely implementation of appropriate antimicrobial therapy. A 3-D approach to judicious antimicrobial use focuses on the de-escalation of systemic antimicrobial therapy, design of dosing regimens, and decontamination of the surgeon, patient, and environment. De-escalation can be accomplished in part through proper antimicrobial prophylaxis. Dosing regimens should be designed to maximize efficacy and minimize resistance. Decontamination includes disinfection of inanimate surfaces and timely application of appropriate antiseptics at concentrations that maximize efficacy.

Comparison of phenobarbital with bromide as a first-choice antiepileptic drug for treatment of epilepsy in dogs.

OBJECTIVE: To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs. DESIGN: Double-blinded, randomized, parallel, clinical trial. ANIMALS: 46 AED-naïve dogs with naturally occurring epilepsy. PROCEDURES: Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs. RESULTS: Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 µg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], p.o., q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], p.o., q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end. CONCLUSIONS AND CLINICAL RELEVANCE: Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.

Pharmacokinetics of buprenorphine in a sodium carboxymethylcellulose gel after buccal transmucosal administration in dogs.

Alternatives to intravenous administration of opioids are needed in veterinary medicine. Previous research suggests that opioids can be administered through the buccal mucosa in dogs. This study reports the pharmacokinetics of buprenorphine HCl (0.05 mg/kg) administered transmucosally in six dogs compared with those of buprenorphine HCl (0.015 mg/kg) administered intravenously. The results suggest that the pharmacokinetics of buprenorphine HCl administered intravenously or transmucosally are similar and that transmucosal administration may be considered as a noninvasive alternative to intravenous administration.

Ex vivo viability of canine and feline sarcomas: a pilot study.

Assay-based chemotherapeutic protocols are common in human gynecologic oncology, most notably for patients with ovarian or breast cancer. The current study examines ex vivo incubation conditions necessary for the assessment of sarcomatous tumor response to potential chemotherapeutic drugs. Slices of sarcomatous tumors were incubated in one of two culture media. Viability indices were measured and compared across time and between media. Neither medium was sufficient to support the growth of sarcomatous tumor tissue slices based on the indices studied. It is likely that sarcomatous tumors require a different approach for ex vivo assessment than their epithelial counterparts. Our long-term goal is to incubate tumor slices with chemotherapeutic agents to predict the in vivo tumor response based on the maintenance or loss of slice viability within this system.

Interpreting culture and susceptibility data in critical care: perks and pitfalls.

PROBLEM: The need for immediate, effective antimicrobial therapy in the critical care patient must be tempered by approaches which simultaneously minimize emergence of antimicrobial resistance. Ideally, therapy will successfully resolve clinical signs of infection, while eradicating infecting pathogens such that the risk of resistance is avoided. Increasing limitations associated with empirical antimicrobial choices direct the need for culture and susceptibility data as a basis of therapy. Even so, such in vitro data should be utilized within its limitations. OBJECTIVES: To demonstrate the attributes and limitations of patient and population culture and susceptibility (pharmacodynamic) data in the selection of antimicrobial drugs and to demonstrate the design of individualized dosing regimens based on integration of pharmacodynamic (PD) and pharmacokinetic (PK) data. DIAGNOSIS: Limitations in culture and susceptibility testing begin with sample collection and continue through drug selection and dose design. Among the challenges in interpretation is discrimination between pathogens and commensals. Properly collected samples are critical for generation of data relevant to the patient's infection. Data are presented as minimum inhibitory concentrations (MICs). The MIC facilitate selection of the most appropriate drug, particularly when considered in the context of antimicrobial concentrations achieved in the patient at a chosen dose. Integration of MIC data with key PK data yields the C(max):MIC important to efficacy of concentration-dependent drugs and T>MIC, which guides use of time-dependent drugs. These indices are then used to design dosing regimens that are more likely to kill all infecting pathogens. In the absence of patient MIC data, population data (eg, MIC(90)) may serve as a reasonable surrogate. CONCLUSIONS: Properly collected, performed, and interpreted culture and susceptibility data are increasingly important in the selection of and design of dosing regimens for antimicrobial drugs. Integration of PK and PD data as modified by host and microbial factors supports a hit hard, exit fast approach to therapy that will facilitate efficacy while minimizing resistance.

Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5 fluoroquinolones toward pathogens of dogs and cats.

BACKGROUND: Fluoroquinolones are often used interchangeably in dogs and cats. HYPOTHESIS: Predicted therapeutic efficacy differs among fluoroquinolones. ANIMALS: Bacterial pathogens isolated from dogs and cats. METHODS: Using microtube-dilution procedures, percent resistance and 2 pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10), enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for organisms represented by < or = 15 isolates. RESULTS: Percent resistance for all Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin > or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp. and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose, the proportion of isolates for which a target was reached was: ciprofloxacin, enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%), orbifloxacin (51%), and difloxacin (40%); and at the low dose, enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%), marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%). CONCLUSIONS: E. coli resistance to fluoroquinolones approximated 40%. For susceptible isolates, enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices associated with predicted efficacy, but only at the high dose.

Principles of antimicrobial therapy.

The most compelling reason for practicing judicious antimicrobial use is to facilitate therapeutic success. The definition of therapeutic success has changed in recent years, however; not only does success include eradication of infection, but it must now include avoidance of resistance. If the goal of antimicrobial therapy is to achieve sufficient concentrations at the site of infection such that the infecting organism is killed, therapy should be successful.

Veterinary compounding in small animals: a clinical pharmacologist's perspective.

The advent and growth of veterinary compounding and the increasing role of the pharmacist in drug dispensing, including compounding, should be embraced by the veterinary profession. For selected patients, extemporaneous compounding of prescriptions is necessary and beneficial for optimal treatment. By its nature, however, compounding is individualized and fraught with risks of failure. Pet owners should be informed of the risks associated with using a compounded product and consent to therapy based on disclosure that the use of the product may be scientifically unproven. As the pharmacy profession increases its efforts to define and ensure its role in veterinary medicine, and as the regulatory agencies consider changes in the regulations that increase the flexibility of animal drug compounding, the veterinary profession must implement actions that protect the patient and the public. It is indeed the responsibility of the veterinarian to ensure the safety and therapy of any prescribed therapeutic intervention, and failure to do otherwise places the patient and pet owner as well as the veterinarian at risk.

Balancing fact and fiction of novel ingredients: definitions, regulations and evaluation.

Veterinarians have an opportunity to help educate their clients regarding the safety and efficacy of novel ingredients used by their clients. This is no small task because of the lack of acceptable information. Clients should be counseled regarding the lack of scientific evidence and be encouraged to discriminate fact from fiction, including many testimonials. Safety should be of primary concern, and clients should be encouraged not to neglect traditional therapies in lieu of novel ingredients unless clinical evidence of efficacy exists. Quality assurance is equally important and cannot be underestimated. Clients are likely to resort to less expensive products. Clients should be directed to the advice offered by the Arthritis Foundation as follows: "When a supplement has been studied with good results, find out which brand was used and buy that." Although skepticism is encouraged regarding any unknown product with medicinal indications, open mindedness should also guide the veterinarian as these products are considered. Indeed, veterinarians should take actions to ensure that the use of these compounds is accomplished within the confines of the veterinary-client-patient relationship, thus ensuring the role of the veterinarian in the health and well-being of animals, regardless of the modality of therapy. The veterinary profession should support the development of standards that might guide manufacturers of novel ingredients to meet criteria that protect the consumer. Likewise, we should encourage manufacturers and agencies to fund veterinary clinical trials to provide evidence for the use of these potentially exciting compounds. Above all else, the veterinarian needs to become a credible resource of information about the possible role of these products. The lack of a regulatory mechanism that establishes the safety and efficacy of these products is not justification for ignoring the potential therapeutic benefit of some of these products. Veterinarians should follow the advice of the Arthritis Foundation, which notes: "Since glucosamine is self-prescribed ... health care professionals are not regarded [to have] objective advice. This situation must change. It is time for the profession to accommodate the possibility that many nutritional products may have valuable therapeutic effects" [61].

Disposition of sulfadimethoxine in male llamas (Llama glama) after single intravenous and oral administrations.

This study determined the disposition of sulfadimethoxine in six, healthy, adult, gelded male llamas (Llama glama) by using a nonrandomized crossover design with i.v. dosing (58.8 +/- 3.0 mg/kg based on metabolic scaling) followed by oral dosing (59.3 mg/kg +/- 8.3). Blood samples were collected intermittently for a 72-hr period, and serum sulfadimethoxine concentrations were quantified using high-performance liquid chromatography. Serum sulfadimethoxine concentrations across time were subjected to standard pharmacokinetic analysis based on linear regression. Mean maximum serum concentration after oral dosing was 23.6 +/- 14.9 microg/ml, and extrapolated peak concentration after i.v. administration was 246.6 +/- 15.8 microg/ml. Total clearance of sulfadimethoxine was 45.4 +/- 13.9 L/kg. Half-lives after i.v. and oral administration were 541 +/- 111 min and 642.4 +/- 204.8 min, respectively. Oral bioavailability was 52.6 +/- 15%. These data suggest that the oral dose administered to llamas in this study, based on metabolic scaling from cattle, may be inadequate when compared with the reported minimum inhibitory concentration (512 microg/ml) breakpoint for sulfadimethoxine.

Disposition and clinical use of bromide in cats.

OBJECTIVE: To establish a dosing regimen for potassium bromide and evaluate use of bromide to treat spontaneous seizures in cats. DESIGN: Prospective and retrospective studies. ANIMALS: 7 healthy adult male cats and records of 17 cats with seizures. PROCEDURE: Seven healthy cats were administered potassium bromide (15 mg/kg [6.8 mg/lb], p.o., q 12 h) until steady-state concentrations were reached. Serum samples for pharmacokinetic analysis were obtained weekly until bromide concentrations were not detectable. Clinical data were obtained from records of 17 treated cats. RESULTS: In the prospective study, maximum serum bromide concentration was 1.1 +/- 0.2 mg/mL at 8 weeks. Mean disappearance half-life was 1.6 +/- 0.2 weeks. Steady state was achieved at a mean of 5.3 +/-1.1 weeks. No adverse effects were detected and bromide was well tolerated. In the retrospective study, administration of bromide (n = 4) or bromide and phenobarbital (3) was associated with eradication of seizures in 7 of 15 cats (serum bromide concentration range, 1.0 to 1.6 mg/mL); however, bromide administration was associated with adverse effects in 8 of 16 cats. Coughing developed in 6 of these cats, leading to euthanasia in 1 cat and discontinuation of bromide administration in 2 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Therapeutic concentrations of bromide are attained within 2 weeks in cats that receive 30 mg/kg/d (13.6 mg/lb/d) orally. Although somewhat effective in seizure control, the incidence of adverse effects may not warrant routine use of bromide for control of seizures in cats.

Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin in dogs following single oral administration of enrofloxacin at 7.5, 10, or 20 mg/kg.

Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin were monitored following oral administration of enrofloxacin at 7.5, 10, and 20 mg/kg to six healthy female bloodhounds using a randomized crossover design. Plasma samples were collected at various times over 24 hours following drug administration. Both the parent drug and its metabolite were detected by high-performance liquid chromatography, and plasma drug concentration-versus-time curves were subjected to noncompartmental pharmacokinetic analysis. Descriptive statistics were determined for each dosage, and comparisons were made among dosage groups for selected pharmacokinetic parameters. Increasing dosages of enrofloxacin resulted in increased plasma concentrations of both enrofloxacin and ciprofloxacin. Maximum concentration (Cmax) was 2.12 +/- 0.59, 2.1 +/- 0.34, and 4.74 +/- 1.05 mcg/ml for enrofloxacin and 1.30 +/- 0.31, 1.30 +/- 0.32, and 1.86 +/- 0.35 mcg/ml for ciprofloxacin when enrofloxacin was given at dosages of 7.5, 10, and 20 mg/kg, respectively. Cmax and area under the curve (AUC) for both enrofloxacin and ciprofloxacin were significantly greater at 20 mg/kg than at 7.5 and 10 mg/kg. Disappearance half-life was similar for all dosages, ranging from 4.6 to 5.2 hours for enrofloxacin and 8.8 to 10.7 hours for ciprofloxacin. Ciprofloxacin contributed up to 42% of the Cmax and up to 55% of the AUC of the total (enrofloxacin plus ciprofloxacin). For organisms with a minimum inhibitory concentration (MIC) of 0.5 mcg enrofloxacin/ml, an inhibitory quotient (IQ; Cmax:MIC) of 8 or more was achieved in plasma only at 20 mg/kg.