Diagnostic and therapeutic challenges for dogs with urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli

Faye A. Hartmann Clinical Pathology Laboratory, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Lana Fox Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843.

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Barry Fox Division of Infectious Diseases, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705.

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Katrina Viviano Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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The most important challenge resulting from years of antimicrobial use is the increasing worldwide emergence of resistant bacterial populations. Bacteria continuously evolve in response to antimicrobial exposure and selective pressures, resulting in emergence and dissemination of new mechanisms of antimicrobial resistance. For example, carbapenem-resistant Enterobacteriaceae and ESBL-producing Enterobacteriaceae are becoming increasingly more apparent in people, animals, and the ecosystem.1–3

Infections, including urinary tract infections, due to ESBL-producing Enterobacteriaceae have become more common in human and veterinary medicine during the past decade.4–7 In an unpublished review of records, we found that over the 2-year period from January 2016 through December 2017, 75% and 72%, respectively, of the ESBL-producing Enterobacteriaceae cultured from outpatients at the University of Wisconsin Hospital and Clinics and University of Wisconsin Veterinary Care were obtained from urine. Further, at the University of Wisconsin Hospital and Clinics and University of Wisconsin Veterinary Care, 4% and 7%, respectively, of the Escherichia coli isolates obtained from outpatient urine samples were ESBL-producing E coli. Because ESBL-producing E coli are often resistant to antimicrobials commonly used to treat urinary tract infections, including most β-lactams, potentiated sulfonamides, and fluoroquinolones,7–10 management of these infections poses important diagnostic and therapeutic challenges. In addition, laboratory tests may not accurately identify ESBL-producing organisms,11 and therapeutic options are limited owing to the presence of antimicrobial resistance. Thus, practitioners in human and veterinary medicine should be aware of the latest information regarding appropriate methods for microbiological detection of ESBL-producing E coli and the correct interpretation of susceptibility results and proper selection of antimicrobial treatment.

A Practical Illustration of the Problem

An 8-year-old 25-kg (55-lb) spayed female mixed-breed (Samoyed-Siberian Husky) dog that was found as a stray on the interstate during the winter season was brought to a local animal shelter in the Midwest, where antimicrobial treatment for kennel cough was initiated. Because antimicrobial-resistant strains of Bordetella spp had previously been isolated at the shelter, the treatment protocol included chloramphenicol and amikacin (dosages unknown) for 2 weeks, followed by amoxicillin-clavulanic acid (375 mg, PO, q 12 h) for 2 weeks.

Two weeks after antimicrobial treatment was completed, the dog was released to a foster home, but within 72 hours, the dog began to exhibit clinical signs consistent with lower urinary tract infection (ie, pollakiuria, stranguria, restlessness, and anxiety during urination). The dog was evaluated by the emergency service at University of Wisconsin Veterinary Care, and abnormalities noted during physical examination included frequent posturing to urinate with only a small volume of urine produced, urine-stained hind limbs with perivulvar dermatitis, and hyperemic vulvar mucosa. Focused assessment with sonography in trauma examination (FAST) of the urinary bladder documented a small bladder and an absence of free abdominal fluid, ruling out lower urinary tract obstruction or bladder rupture. Pending results of urine bacterial culture and antimicrobial susceptibility testing, the dog was initially treated with prazosin (2 mg, PO, q 8 h) for bladder and urethral spasms and enrofloxacin (272 mg, PO, q 24 h). Enrofloxacin was chosen empirically on the basis of recent exposure to antimicrobials from multiple classes, including amoxicillin-clavulanic acid (in the past 4 weeks) and the high potential for a drug-resistant uropathogen. Additional supportive treatments included tramadol (100 mg, PO, q 8 to 12 hours) to relieve discomfort and topical application of a solution containing 2% miconazole, 2% chlorhexidine, and tromethamine-EDTA once a day to treat the perivulvar dermatitis.

Forty-eight hours after initiation of treatment, an ESBL-producing E coli was cultured from the urine. Although susceptibility results (Table 1) indicated in vitro resistance to enrofloxacin, mild clinical improvement was reported in association with the initial enrofloxacin treatment. Nevertheless, enrofloxacin was discontinued and replaced with nitrofurantoin (100 mg, PO, q 8 h for 7 days). With resolution of the pollakiuria and stranguria, prazosin was discontinued. Three days after completion of the nitrofurantoin regimen, the dog no longer had clinical signs of urinary tract infection. However, bacteriuria (> 100,000 colony-forming units/mL of 2 ESBL-producing E coli isolates) persisted on follow-up culture of a urine sample obtained 2 weeks later.

Table 1—

Results of susceptibility testing of an ESBL-producing Escherichia coli isolate recovered from a urine sample from an 8-year-old 25-kg (55-lb) spayed female mixed-breed (Samoyed-Siberian Husky) dog that had signs of lower urinary tract infection.

Antimicrobial agentMIC (μg/mL)Interpretation
AmpicillinV≥ 32R
Amoxicillin-clavulanic acidV*8R
Ampicillin-sulbactam≥ 32R
Piperacillin≥ 128R
CefalotinV≥ 64R
CefazolinV≥ 64R
Cefotaxime≥ 64R
Cefotetan≤ 4S
Cefoxitin16I
Cefpodoxime≥ 8R
Ceftazidime16R
Ceftizoxime4R
Ceftriaxone≥ 64R
Imipenem≤ 0.25S
Meropenem≤ 0.25S
Ciprofloxacin≥ 4R
EnrofloxacinV≥ 2R
AmikacinV≥ 64R
GentamicinV≥ 16R
ChloramphenicolNDR
Tetracycline≤ 1S
FosfomycinNDS
Nitrofurantoin≤ 16S
Trimethoprim-sulfamethoxazole≤ 20S

Interpretations were based on CLSI guidelines20 for isolates from human patients unless otherwise indicated. Tetracycline susceptibility was used to predict doxycycline susceptibility.

Interpretation was based on CLSI guidelines for veterinary isolates.21

Interpretation was changed to resistant because of high MIC.23

I = Intermediate susceptibility. ND = Not determined; susceptibility test results were derived from disk diffusion testing. R = Resistant. S = Susceptible.

ESBL-producing E coli

The first antimicrobial-resistant bacteria found to be producing ESBLs were Enterobacteriaceae, predominantly E coli and Klebsiella pneumoniae,10,12 and since the 1980s, the prevalence of ESBL-producing isolates has increased worldwide in both human5 and companion animal1,6,13 medicine. Resistance determinants encoding for ESBLs are often found on plasmids (extrachromosomal DNA segments), which facilitate transfer among Enterobacteriaceae and may carry additional resistance factors.10,13–15 Extended spectrum β-lactamases are a diverse group of enzymes that inactivate most β-lactam antimicrobials by hydrolyzing the β-lactam ring, and ESBL-producing Enterobacteriaceae are resistant to aminopenicillins, ureidopenicillins, cephalosporins, and monobactams. However, ESBL-producing isolates are susceptible to cephamycins (cefoxitin and cefotetan) and carbapenems, which aids in their identification.

The uropathogen most frequently isolated from dogs is E coli, and the recommended first-line choices for antimicrobial treatment of uncomplicated lower urinary tract infections in dogs are amoxicillin and potentiated sulfonamides.16 Effective initial empirical treatment for ESBL-producing uropathogens is challenging owing to cross-resistance to other antimicrobial classes. For example, ESBL-producing uropathogenic E coli strains previously isolated from the urine of dogs and cats were found to be resistant to ampicillin, amoxicillin-clavulanic acid, and cephalosporins.7,17 Resistance to fluoroquinolones, nalidixic acid, tetracycline, and sulfamethoxazole-trimethoprim has also been detected. Ultimately, effective antimicrobial treatment for infections caused by ESBL-producing bacteria is guided by results of in vitro antimicrobial susceptibility testing, which not only carries a degree of complexity but may not always correlate with in vivo susceptibility. For this reason, it may be necessary to use PK-PD data to determine whether antimicrobials to which an isolate is susceptible will reach the site of infection and whether the isolate's MIC can be attained on the basis of the prescribed antimicrobial dosage.

Detection of ESBL-producing Isolates

Before 2010, laboratory detection of ESBL-producing bacteria relied on screening isolates for resistance to cefpodoxime, ceftazidime, cefotaxime, ceftriaxone, or aztreonam, followed by confirmatory testing for inhibition of this resistance by clavulanic acid, a β-lactamase inhibitor.18 Strains confirmed to be producing ESBLs were considered to be resistant to all penicillins, cephalosporins, and aztreonam, regardless of the MIC and breakpoint interpretation in vitro, and susceptibility results for these antimicrobials were edited to resistant. However, the susceptibility interpretation for the cephamycins and various combinations containing a β-lactamase inhibitor were not edited for ESBL-producing strains, owing to continued activity in vivo, if the MICs were within the appropriate interpretation range.

Interpretation of antimicrobial susceptibility test results relies on the use of established clinical breakpoints to define isolates as susceptible, intermediate, or resistant. A popular organization that develops standardized guidelines used in the United States and worldwide is the CLSI. In 2010, CLSI published revised breakpoint interpretive criteria for cephalosporins and aztreonam (ie, use of lower MICs and larger disk diffusion zone diameters as breakpoints to identify resistance) for Enterobacteriaceae isolated from people.19 Implementation of the new interpretive criteria allowed for discontinuation of routine screening for ESBL production prior to reporting of susceptibility results. Thus, results for penicillins, cephalosporins, or aztreonam no longer required editing from susceptible to resistant. This allowed for more accurate reporting, decreasing the number of false-positive results attributable to resistance mechanisms other than ESBL production. However, if a laboratory chose not to use the new interpretive criteria, routine ESBL screening and confirmatory testing were still recommended with editing of susceptibility interpretations.

Implementation of the new interpretive criteria for Enterobacteriaceae and, if not used, routine testing for ESBL production are still recommended by CLSI in its most current guideline.20 However, the revised breakpoints and interpretive criteria for cephalosporins and aztreonam are based on PK-PD properties in people, and the comparable veterinary CLSI guideline does not have similar revised breakpoints and interpretive criteria for cephalosporins and aztreonam.21 The veterinary guideline does contain a table describing screening for ESBL production and confirmatory testing; however, the table does not indicate how to report results for confirmed ESBL-producing strains. In addition, routine testing for ESBL production is not recommended. The table contains a footnote that recommends testing for ESBL production only when deemed clinically relevant (eg, a bacteremic isolate).

In contrast, we argue that routine testing of veterinary isolates for ESBL production should be endorsed. Because there are multiple types of ESBLs, detection of an ESBL-producing strain can be missed if the laboratory is testing for resistance to only a single third-generation cephalosporin.11 To improve detection, resistance to multiple third-generation cephalosporins should be tested on the basis of the revised lower MICs or larger disk diffusion diameters included in the CLSI interpretive criteria for isolates cultured from people. Alternatively, CLSI-recommended ESBL screening and confirmatory testing should be performed, and all ESBL-producing isolates should be reported as resistant to cephalosporins (except cephamycins), aztreonam, and all penicillins (except for combinations containing a β-lactamase inhibitor) regardless of the MIC and breakpoint interpretation. Until scientific evidence suggests otherwise, this practice should be employed for ESBL-producing isolates from companion animals to prevent any delays in initiation of effective antimicrobial treatment.

Susceptibility Interpretation

For the initial ESBL-producing E coli isolate cultured from the mixed-breed dog described earlier, susceptibility testing was performed with an automated antimicrobial susceptibility systemb and the current, lower, CLSI-recommended cephalosporin and aztreonam MIC interpretive criteria for people, along with ESBL screening and confirmatory testing. In addition, the susceptibility system used a software component to evaluate the resistance profile of the isolate to determine the probable mechanism of resistance. The isolate was identified by the susceptibility system as an ESBL-producing E coli with high MICs for penicillins, cephalosporins, and aztreonam (Table 1). The isolate had intermediate susceptibility to cefoxitin (cephamycin) and was susceptible (MIC, 8 μg/mL) to amoxicillin-clavulanic acid. The isolate was also classified as MDR, because it was resistant to ≥ 3 classes of antimicrobials, including fluoroquinolones, aminoglycosides, and chloramphenicol.22 Although the isolate was initially reported as susceptible to amoxicillin-clavulanic acid and the CLSI does not currently recommend editing a result for amoxicillin-clavulanic acid from susceptible to resistant for an ESBL-producing strain,20 it has been shown that resistance may develop during antimicrobial treatment if an ESBL-producing strain has a high MIC for amoxicillin-clavulanic acid. An amoxicillin-clavulanic acid MIC ≤ 2 μg/mL has not been associated with treatment failure, compared with an MIC ≥ 8 μg/mL.23 Therefore, to avoid a risk of treatment failure and on further review, the amoxicillin-clavulanic acid interpretation was edited to resistant on the basis of the MIC of 8 μg/mL.

The isolate was susceptible to tetracycline (used to predict susceptibility to doxycycline), fosfomycin, nitrofurantoin, and trimethoprim-sulfamethoxazole. The follow-up culture in this dog yielded 2 ESBL-producing E coli isolates that differed in morphological appearance. The susceptibility results of these isolates differed only by 1 dilution for amoxicillin-clavulanic acid and tetracycline, compared with results for the original isolate.

In this case, susceptibility breakpoint interpretations were based on veterinary guidelines when available; otherwise, interpretations developed for people were used. Unfortunately, there are limited veterinary interpretations owing to a lack of sufficient scientific studies. It is therefore important to have the actual MICs included as part of the susceptibility test report, so that appropriate clinical decisions about antimicrobial treatment can be made in conjunction with available published veterinary PK-PD data.

Antimicrobial Treatment

Antimicrobial agents associated with a high rate of clinical success when treating infections caused by ESBL-producing Enterobacteriaceae in people include the carbapenems, piperacillin-tazobactam, and cephamycins. Much less is reported or known about antimicrobials likely to be useful for treating infections caused by ESBL-producing strains in companion animals. A recent study24 reported that > 90% of ESBL-producing E coli isolates from dogs and cats were susceptible to carbapenems and also to amikacin, nitrofurantoin, fosfomycin, and piperacillin-tazobactam.

Carbapenems are often the IV treatment choice for serious infections caused by ESBL-producing Enterobacteriaceae. However, carbapenems must be used judiciously in veterinary medicine owing to increases in the number of carbapenemase-producing microorganisms and public health concerns.1,2,25–27 Cephamycins (eg, cefoxitin) have been used for treating infections caused by ESBL-producing strains in people; however, efficacy studies in people are lacking. Recently, it was reported28 that cefoxitin may be a good candidate for treating urinary tract infections in people caused by ESBL-producing E coli. Unfortunately, the study had several limitations including a small sample size. Hence, definitive treatment with cephamycins has not become a standard of care.

In people, an alternative to the use of carbapenems is piperacillin-tazobactam, which combines a β-lactam with a β-lactamase inhibitor, and this combination has been shown to be effective for treatment of people with infection caused by ESBL-producing isolates when those isolates are found to be susceptible to the combination in vitro.29 However, piperacillin-tazobactam is not approved for veterinary use, and its use is not recommended and is discouraged in veterinary patients if other options are available. In addition, its use is not supported by efficacy studies in companion animals. Another β-lactam-β-lactamase-inhibitor combination commonly used in veterinary medicine, amoxicillin-clavulanic acid, may be worth considering for oral treatment of urinary tract infections caused by ESBL-producing E coli if the in vitro MIC of the isolate is ≤ 2 μg/mL.23 However, studies have not been performed in companion animals and thus efficacy is not known.

Practical treatment options for infections caused by ESBL-producing bacteria are limited not only because of resistance, but also because of a lack of availability of suitable antimicrobials, practical considerations regarding dosing in companion animals, and concerns related to judicious use of antimicrobials critical to human health. Therapeutic options for treating urinary tract infections caused by ESBL-producing strains in companion animals are further limited because of a lack of PK-PD data and efficacy studies. On the basis of in vitro susceptibility testing results, alternative orally administered antimicrobials that were considered for treating the ESBL-producing uropathogen isolated from the dog described previously included fosfomycin, trimethoprim-sulfamethoxazole, nitrofurantoin, and doxycycline.

Fosfomycin is a low-molecular weight antimicrobial available for oral administration that inhibits peptidoglycan synthesis and is used in the treatment of uncomplicated cystitis in people.30 Susceptibility to fosfomycin is not reported by many microbiology laboratories because fosfomycin is not available as part of automated laboratory panels and requires disk diffusion testing for susceptibility determination. There is limited experience with the use of fosfomycin in companion animal medicine, but ESBL-producing E coli isolates appear to maintain high susceptibility, as is reported31 for isolates from people (ie, approx 95% of ESBL-producing E coli isolates remain susceptible to fosfomycin).

The final in vitro susceptibility test results for the dog described previously indicated that the isolate was resistant to antimicrobial classes prescribed in the past 4 weeks and to the antimicrobial chosen for empirical treatment, leaving few treatment options. The dog's initial partial clinical response to enrofloxacin was likely a result of high concentrations achieved in the urine of dogs (173 to 263 μg/mL), relative to serum (1.41 μg/mL).32,33 A partial response to antimicrobial treatment is not uncommon with antimicrobials that achieve high concentrations in the urine even if in vitro resistance is detected for an isolate. Treatment with trimethoprim-sulfamethoxazole was not initially pursued owing to the anticipated duration of treatment, the lack of information on optimal treatment durations in companion animal medicine,16 and the risk of idiosyncratic hypersensitivity reactions.34,35 However, if short-duration treatment was anticipated, trimethoprim-sulfamethoxazole may have been a rational choice for this dog. No adverse effects were associated with treatment with trimethoprim-sulfamethoxazole for 3 days in dogs with acute uncomplicated bacterial cystitis.36

Owing to its reportedly low urinary excretion,16,37 treatment with doxycycline was not pursued in this dog. However, in people, doxycycline is successfully used as an alternative for treating urinary tract infections when the isolate is susceptible. It is often used for people with allergies to penicillins, when the isolate is resistant to first-line antimicrobial choices, or if the isolate is resistant to nitrofurantoin. Although low urinary excretion of doxycycline has been reported for dogs, administration of doxycycline at a dose of 5 mg/kg (2.27 mg/lb) will achieve a concentration of 53 μg/mL in the urine of dogs.37 Therefore, in instances when the E coli MIC for doxycycline is ≤ 4 μg/mL, use of doxycycline may be a clinically relevant choice for treating urinary tract infections in dogs caused by ESBL-producing E coli.

For the previously described dog, treatment with nitrofurantoin was initiated on the basis of in vitro susceptibility and the ability to achieve high urinary concentrations (> 60 μg/mL) of nitrofurantoin in the bladder.38 Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that alter bacterial ribosomal proteins, inhibiting growth via multiple targets, including bacterial protein, DNA, and RNA, and obstructing cell wall synthesis.39 Nitrofurantoin is not widely used in veterinary medicine owing to its pharmacokinetics and adverse clinical effects. Anecdotal reports suggest gastrointestinal upset (eg, vomiting) may occur in dogs treated with nitrofurantoin PO.38 The dog tolerated the 7 days of nitrofurantoin treatment without gastrointestinal upset or other adverse effects. Use of nitrofurantoin is ideally reserved for the oral treatment of resistant urinary tract infections limited to the bladder.40

Case Follow-up

Following treatment with nitrofurantoin, the dog's bacteriuria remained subclinical over the next 20 weeks in the absence of any additional antimicrobial therapy. Subclinical bacteriuria is not well described in companion animal medicine41 and remains controversial within the profession, in part owing to the difficulty of defining the presence of clinical signs in dogs. This raises the question of whether to withhold antimicrobial treatment as a principle of judicious use (antimicrobial stewardship) and reserve antimicrobial treatment for when clinical signs are present, especially with MDR pathogens. In people, asymptomatic bacteriuria is common, especially in women over the age of 60, and is not associated with an increased mortality rate. Thus antimicrobial treatment is not recommended.42,43

Five months after the dog's initial acute lower urinary tract infection, clinical signs of pollakiuria and stranguria recurred. Empirical treatment with nitrofurantoin (chosen on the basis of previous susceptibility because bacterial culture of a urine sample was not performed) and prazosin resolved clinical signs. Proteus mirabilis (> 100,000 colony-forming units/mL) with a broad susceptibility pattern was isolated from the urine following antimicrobial treatment. Diagnostic testing subsequently identified additional risk factors for persistent bacteriuria including a nephrolith in the right kidney, a functional thyroid carcinoma, and urinary incontinence following ovariohysterectomy. The thyroid mass was surgically excised, and the spay incontinence was controlled with phenylpropanolamine. This dog's complicated clinical course demonstrated the importance of identifying risk factors, including comorbidities, to minimize recurrent or persistent infections, especially when an MDR pathogen is identified.44

Antimicrobial Stewardship

The CDC has encouraged antimicrobial stewardship in human medicine for both inpatient45 and, more recently, outpatient settings.46 In veterinary medicine, the AVMA has formed a Task Force on Antimicrobial Stewardship in Companion Animal Practice47 and the US FDA's Center for Veterinary Medicine has provided Key Initiatives for Antimicrobial Stewardship.48 The basic principle of antimicrobial stewardship is to use antimicrobials in a judicious manner in an effort to limit the emergence of pathogen resistance and prolong the useful life of antimicrobials.

Selective pressure for emergence of antimicrobial-resistant pathogens is an inherent outcome of antimicrobial use, with overprescribing being one of the factors associated with the evolution of resistance.49 Antimicrobial overprescribing in the United States is estimated to occur in 30% to 50% of human cases.49,50 Much less is known about antimicrobial overprescribing in companion animal medicine; however, recent literature documents similar challenges and suggests comparable estimates of inappropriate use.51–59

As in the dog described earlier, MDR bacterial pathogens are becoming more of a reality in veterinary medicine. This dog's comorbidities as well as previous inappropriate antimicrobial use contributed to the dog's clinical course. In people, recent antimicrobial use, most commonly with third- or fourth-generation cephalosporins or fluoroquinolones, is an important risk factor for development of infection with ESBL-producing uropathogens.44 The need for more widespread stewardship of antimicrobial use within veterinary care facilities and participation in national surveillance programs remains apparent.60,61

Conclusions

Antimicrobial-resistant bacteria, especially those causing urinary tract infections in people and companion animals, are likely to increase in incidence. Across professions, the clinical challenges presented by antimicrobial-resistant pathogens are how best to successfully manage cases when effective antimicrobial choices are limited and preventing further emergence of bacterial resistance as we proceed in this postantimicrobial era.62 Limited data are available on treatment outcomes of infections caused by ESBL-producing pathogens in companion animal medicine. The case described here and the follow-up discussion highlight the need for health-care professionals to be knowledgeable about newer mechanisms of resistance, familiar with interpreting susceptibility results, and increasingly responsible for antimicrobial stewardship.

The emergence of antimicrobial-resistant pathogens, including ESBL-producing pathogens, in both human and veterinary medicine demonstrates the complexity of in vitro susceptibility testing, reporting, and interpretation.10 This is particularly true for veterinary isolates, as there are limited veterinary antimicrobial susceptibility breakpoint interpretations owing to the lack of sufficient scientific studies. It is therefore important to have actual MICs reported as part of the susceptibility test result so that available published veterinary PK-PD data can be evaluated and appropriate clinical decisions about antimicrobial treatment can be made.

As a profession, veterinarians lag behind physicians in the use of formal antimicrobial stewardship efforts. Antimicrobial stewardship needs to start at the initiation of empirical antimicrobial therapy, even when bacterial culture and susceptibility testing are pursued. As in the case described here, empirical antimicrobial treatment is common for dogs with acute dysuria and examination findings consistent with a lower urinary tract infection. When antimicrobial treatment is indicated, the most narrow-spectrum antimicrobial for the shortest duration necessary is advised. For clinical situations when bacterial culture and susceptibility testing may not be feasible, response to initial antimicrobial treatment within 72 hours can be supportive of the clinical diagnosis. However, in instances when there is no response to rational empiric antimicrobial treatment within 48 to 72 hours and in dogs with a more complicated clinical course, further diagnostic testing, including bacterial culture of the urine and antimicrobial susceptibility testing of clinically important pathogens, is recommended. As demonstrated in the case described here, identifying risk factors, including comorbidities and previously prescribed antimicrobial treatment, is essential. This is especially important when an antimicrobial-resistant pathogen is identified owing to the potential risk of antimicrobial treatment failure resulting in recurrent or persistent infections. Importantly, practitioners must keep in mind that in some clinical situations, subclinical bacteriuria may not warrant further treatment.

Moving the profession forward requires defining a path to reach the unifying goal of reducing inappropriate antimicrobial use. For this to happen, more clinical veterinary PK-PD studies are needed. In addition, veterinarians need to be knowledgeable of the limitations of in vitro susceptibility testing, should be informed on how to correctly interpret susceptibility test results, and should document all prescriptions. Finally, increased veterinary participation in antimicrobial stewardship is warranted, which ideally should include an interdisciplinary one-health approach to involve collaboration between physicians and veterinarians.

ABBREVIATIONS

CLSI

Clinical Laboratory Standards Institute

ESBL

Extended-spectrum β-lactamase

MDR

Multidrug resistant

MIC

Minimum inhibitory concentration

PK-PD

Pharmacokinetic-pharmacodynamic

Footnotes

a.

MiconaHex+Triz shampoo, Dechra Veterinary Products LLC, Overland Park, Kan.

b.

Vitek, BioMérieux, Durham, NC.

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