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Determining empirical antibiotic choices in cats with urinary tract infections

KuKanich K, Lubbers B, Salgado B. Amoxicillin and amoxicillin-clavulanate resistance in urinary Escherichia coli antibiograms of cats and dogs from the midwestern United States. J Vet Intern Med. 2020;34:227–231.

Responsible antimicrobial stewardship in both the human and veterinary fields is now a scientific and moral imperative discussed frequently in professional and public media.  In the last several years, a number of human and veterinary professional organizations and working groups have published guidelines advocating conservative use of antimicrobials in common disease states such as respiratory and urinary tract infections. In particular, the International Society for Companion Animal Infectious Diseases (ISCAID) published its most recent guidelines for the treatment of urinary tract infections (UTIs) in dogs and cats less than one year ago.

In many cases, results of a urinanalysis and the presence of clinical signs of a UTI in a companion animal patient may dictate initiation of antibiotic therapy either prior to or without a urine antimicrobial culture and antibiotic sensitivity testing. Making a rational, evidence-based empirical choice of an appropriate antimicrobial in these situations can improve patient comfort, relieve client frustration, and also decrease the risk of infection ascending into or exacerbating in the upper urinary tract.  This is a situation in which an antibiogram, which lists the percentage of a bacterial isolate susceptible to a particular antimicrobial drug, can be useful in planning treatment of a UTI.

Escherichia coli is one of the most common uropathogens in companion animals. In this study of E. coli isolates cultured from the urine of 143 cats and 640 dogs seen in private (n = 448) and university (n = 335) practice in the midwestern United States between 2013 and 2017, antibiograms for 10 common antimicrobial agents were reviewed retrospectively. The antibiograms were created from the urine culture and sensitivity data. Sixty-two (43%) of the E. coli isolates from cats came from university practice, while 81 (57%) came from cats seen in private practice.

Only the first culture for a calendar year for an individual cat or dog was used in developing the antibiogram.  Because this was a retrospective study, data regarding previous antimicrobial therapy or comorbidities in many individual patients included in the study were not consistently available. Also, there was no information regarding urine collection method, and no consistent time established between urine collection and plating for culture.  E. coli-positive samples representing subclinical bacteriuria were probably also included in the study, as there was no consideration of bacterial load (colony forming units) in the sample.

Antibiotics included in the antibiograms for both species were amoxicillin/clavulanate, ampicillin (a surrogate for amoxicillin), cefovecin, cefpodoxime, cephalexin, enrofloxacin, marbofloxacin, orbifloxacin, pradofloxacin, and trimethoprim/sulfamethoxazole.  Breakpoints in minimal inhibitory concentration for each antibiotic in each species associated with susceptibility, intermediate susceptibility, and resistance were obtained from references in the veterinary medical literature. In creating the antibiograms, isolates reported as having intermediate susceptibility to an agent were not considered as susceptible at all.

In contrast to the E. coli isolates from dogs, all of the E. coli isolated from cat urine were found to be significantly resistant to ampicillin, amoxicillin, and amoxicillin-clavulanate.  These agents are recommended as first-line antimicrobials for UTI in dogs and cats by the most recent (2019) ISCAID guidelines.  However, the authors caution that this is not a reason to avoid prescribing these medications in cats with UTI, but may indicate the need to re-evaluate the breakpoint used to determine bacterial sensitivity to these antibiotics in cats.

In dogs, the breakpoint for sensitivity to these beta-lactams is < 8 µg/mL, while in cats this breakpoint is set at < 0.25 µg/mL. Because concentrations for amoxicillin and amoxicillin-clavulanate in feline urine have not been reported, the breakpoints for susceptibility to these antimicrobials are determined from plasma drug concentrations, and are conservative.  The susceptibility breakpoints for amoxicillin and amoxicillin-clavulante in canine urine are UTI-specific, based on urine concentration data for these drugs; similar information needs to be determined for feline urine samples, so that a UTI-specific breakpoint for these two antimicrobials is available for cats.  If the feline UTI-specific breakpoint is less conservative than that determined from plasma drug concentrations for amoxicillin and amoxicillin-clavulanate, then more E. coli isolates from cat urine would be reported as susceptible to these affordable, recommended first-line agents. If the canine UTI-specific breakpoint of < 8 µg/mL is applied to the feline samples, the percentage of isolates from these samples reported as susceptible to amoxicillin and amoxicillin-clavulanate would be 89% and 99%, respectively.

Over 90% of the E. coli isolates from feline urine were susceptible to all of the other antibiotics tested; <6% of the isolates from feline urine demonstrated resistance to any antimicrobial agent other than amoxicillin or amoxicillin-clavulanate. The findings in this study are regional, however, and may not apply to E. coli isolates from cats and dogs in other parts of the USA or the world.  Also, whether or not bacterial isolates come from patients with or without azotemia, or from clinical UTIs or subclinical bacteriuria, may influence antibiogram results and their utility in individual patients. [PJS]

See also:

Moyaert H, Morrissey I, et al. Antimicrobial susceptibility monitoring of bacterial pathogens isolated from urinary tract infections in dogs and cats across Europe: ComPath results. Microb Drug Resist. 2017; 23: 391‐ 403.