Dawn M. Boothe

Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases

Urinary tract disease is a common reason for use (and likely misuse, improper use, and overuse) of antimicrobials in dogs and cats. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, guidelines for diagnosis and management of urinary tract infections were created by a Working Group of the International Society for Companion Animal Infectious Diseases. While objective data are currently limited, these guidelines provide information to assist in the diagnosis and management of upper and lower urinary tract infections in dogs and cats.

Molecular Characterization of Resistance to Extended-Spectrum Cephalosporins in Clinical Escherichia coli Isolates from Companion Animals in the United States

ABSTRACT Resistance to extended-spectrum cephalosporins (ESC) among members of the family Enterobacteriaceae occurs worldwide; however, little is known about ESC resistance in Escherichia coli strains from companion animals. Clinical isolates of E. coli were collected from veterinary diagnostic laboratories throughout the United States from 2008 to 2009. E. coli isolates (n = 54) with reduced susceptibility to ceftazidime or cefotaxime (MIC ≥ 16 μg/ml) and extended-spectrum-β-lactamase (ESBL) phenotypes were analyzed. PCR and sequencing were used to detect mutations in ESBL-encoding genes and the regulatory region of the chromosomal gene ampC. Conjugation experiments and plasmid identification were conducted to examine the transferability of resistance to ESCs. All isolates carried the blaCTX-M-1-group β-lactamase genes in addition to one or more of the following β-lactamase genes: blaTEM, blaSHV-3, blaCMY-2, blaCTX-M-14-like, and blaOXA-1. Different blaTEM sequence variants were detected in some isolates (n = 40). Three isolates harbored a blaTEM-181 gene with a novel mutation resulting in an Ala184Val substitution. Approximately 78% of the isolates had mutations in promoter/attenuator regions of the chromosomal gene ampC, one of which was a novel insertion of adenine between bases −28 and −29. Plasmids ranging in size from 11 to 233 kbp were detected in the isolates, with a common plasmid size of 93 kbp identified in 60% of isolates. Plasmid-mediated transfer of β-lactamase genes increased the MICs (≥16-fold) of ESCs for transconjugants. Replicon typing among isolates revealed the predominance of IncI and IncFIA plasmids, followed by IncFIB plasmids. This study shows the emergence of conjugative plasmid-borne ESBLs among E. coli strains from companion animals in the United States, which may compromise the effective therapeutic use of ESCs in veterinary medicine.

Zonisamide therapy for refractory idiopathic epilepsy in dogs.

Twelve dogs with poorly controlled idiopathic epilepsy were entered into a prospective, open-label, noncomparative study. Oral zonisamide was administered as an additional therapy at a dosage adequate to achieve serum drug concentrations of 10 to 40 microg/mL. Seizure frequency before and after initiation of zonisamide therapy was recorded. A dosing interval of q 12 hours was sufficient to maintain serum zonisamide concentrations within the therapeutic range. The mean dosage of zonisamide required was 8.9 mg/kg q 12 hours. Seven (58%) dogs responded favorably, experiencing a mean reduction in seizures of 81.3%. Five dogs had an increase in seizure frequency. Mild side effects (e.g., transient sedation, ataxia, vomiting) occurred in six dogs.

Anticonvulsant Therapy in Small Animals

Successful control of seizures with anticonvulsant drugs reflects a balance in achieving seizure control while minimizing undesirable drug side effects. Variability in the disposition of anticonvulsants and interaction among them are important confounders of successful therapy. This article will provide a review of selected anticonvulsants, focusing on drugs most likely to control seizures in small animals. The proper use of anticonvulsants will be discussed, with emphasis on differences in individual drug disposition, detection of these differences, and rational approaches to responding to these differences by dose modification. The primary target of discussion will be treatment of generalized, tonic clonic seizures, the most common type afflicting small animals. Opinions regarding anticonvulsive therapy vary among clinicians. Most of the comments and recommendations offered in this discussion reflect observations made from our therapeutic drug monitoring service and completed and ongoing clinical trials that focus on the use of anticonvulsants used either alone or in combination with phenobarbital.

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.

Emergence of a New Delhi Metallo-β-Lactamase (NDM-1)-Encoding Gene in Clinical Escherichia coli Isolates Recovered from Companion Animals in the United States

The rapid spread of extended-spectrum β-lactamases (ESBLs) and quinolone resistance in Escherichia coli in companion animals (1-2) has increased concern among veterinarians9 to find an alternative therapy to treat clinical infections caused by these resistant organisms.…

Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy.

OBJECTIVE To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial. ANIMALS 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital. PROCEDURES Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. RESULTS Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.

Antimicrobial Resistance Profiles and Clonal Relatedness of Canine and Feline Escherichia coli Pathogens Expressing Multidrug Resistance in the United States

BACKGROUND Antimicrobial resistance is increasing among Escherichia coli isolates associated with spontaneous infection in dogs and cats. OBJECTIVES To describe E. coli resistance phenotypes and clonal relatedness and their regional prevalence. ANIMALS Isolates of E. coli (n = 376) collected from dogs and cats in the United States between May and September 2005. METHODS Isolates submitted from the South, West, Northeast, and Midwest regions of the United States were prospectively studied. Phenotype was based on E-test susceptibility to 7 antimicrobials. Isolates were classified as no (NDR), single (SDR), or multidrug resistance (MDR). Clonal relatedness was determined by pulsed-field gel electrophoresis (PFGE). RESULTS One hundred and ninety-three (51%) isolates expressed resistance to at least 1 drug, yielding 42 phenotypes. SDR isolates (n = 84; 44%, 8 phenotypes), expressed resistance most commonly to amoxicillin (30%, n = 25) and least commonly to cefpodoxime (1%, n = 1). MDR isolates (n = 109; 56%, 31 phenotypes) were resistant to amoxicillin (96%, n = 105), amoxicillin-clavulanate (85%, n = 93), and enrofloxacin (64%, n = 70); 18% (n = 20) were resistant to all drugs tested. The frequency of MDR did not differ regionally (P = .066). MDR minimum inhibitory concentrations (MICs) were 6-fold higher than SDR MICs (P < .0001). Dendrograms of 91 isolates representing 25 phenotypes revealed 62 different PFGE profiles. CONCLUSIONS AND CLINICAL IMPORTANCE E. coli strains spontaneously infecting dogs and cats are genetically and phenotypically diverse. Given the current prevalence of MDR among clinical isolates of E. coli in United States, implementation of a robust surveillance program is warranted.

Drugs Affecting the Respiratory System

Differences in the disposition of drugs among exotic animals is a well-recognized hurdle when treating disease. Differences exist in pharmacokinetics, pharmacodynamics, and disease processes. This article focuses on the principles of treating respiratory tract diseases, with the recognition that not all drugs are indicated for use in all exotic species. The discussion begins with a description of respiratory physiology as it pertains to response to drugs, using the mammalian lung as a template. The role of respiratory defense mechanisms in airway protection and disease is addressed. Drugs used to treat the respiratory tract include the bronchodilators and anti-inflammatory drugs, drugs that modify respiratory secretions (e.g., mucolytics, mucokinetics, and expectorants), antitussive drugs, and decongestants. Aerosolization is an important adjuvant for respiratory therapy as long as precautions are met. Infectious diseases are among the more common respiratory diseases encountered, and the discussion includes a focus on the use of antibiotics for treating respiratory tract infections.

Evaluation of outcomes in dogs treated for pyothorax: 46 cases (1983-2001).

OBJECTIVE-To determine the effect of treatment approach on outcome and the appropriateness of initial empirical antimicrobial treatment in dogs with pyothorax. DESIGN-Retrospective case series. ANIMALS-46 dogs with pyothorax confirmed by either (n = 15) or both (31) of the following: intracellular bacteria in pleural fluid or tissue (41) and bacteria recovered via culture of pleural fluid (36). PROCEDURES-Medical records of dogs treated for pyothorax from 1983 through 2001 were reviewed. Data on signalment, history, clinical signs, and treatment and results of diagnostic imaging and cytologic and microbiological evaluations were obtained. Follow-up was performed via reexamination (n = 15) and contact with referring veterinarians (26) and owners (24). RESULTS-46 dogs were treated with at least 1 antimicrobial and thoracocentesis (n = 7; noninvasive group), a thoracostomy tube (26; invasive group) with or without pleural lavage and heparin, or a thoracotomy (13; surgical group) and thoracostomy tube with or without pleural lavage and heparin. Pyothorax recurred in 7 dogs, and 5 of the 7 died or were euthanatized. In the respective groups, the short-term survival rate was 29%, 77%, and 92% and the long-term survival rate was 29%, 71%, and 70%. Pleural lavage and heparin treatment increased the likelihood of short- and long-term survival. Results of antimicrobial susceptibility testing suggested empirical antimicrobial selection was associated with a 35% risk of inefficacy. CONCLUSIONS AND CLINICAL RELEVANCE-In the dogs with pyothorax in this study, favorable treatment effects were achieved with surgery (for short-term survival) and pleural lavage and heparin treatment (for short- and long-term survival). Findings failed to support the hypothesis that invasive (surgical) versus noninvasive treatment of pyothorax in dogs leads to a better long-term outcome.