Veterinarians and pet owners are highly motivated to find discrete, fixable problems when pets are unwell. Owners want the reassurance and sense of control that comes with knowing what the problem is and taking action. Veterinarians want to help our patients, while also satisfying clients. Their expectation is that we offer some clear preventive or therapeutic intervention justifying their time and the expense of coming to see us, as well as reassure them about their pets’ condition. Finally, our medical training often emphasizes diagnosis and treatment as the core responsibility for a doctor; the importance of knowing when not to take action is frequently underemphasized.1,2
Such inherent bias toward finding and treating problems creates discomfort and resistance when scientific evidence suggests we should avoid some tests or treatments. Though there is widespread awareness of the risks of overdiagnosis and overtreatment in human medicine, these are relatively new and controversial concepts in the veterinary field.3,4 My own efforts in this column and elsewhere to suggest we might sometimes do better not to run a test (e.g. pre-anesthetic bloodwork)5 or prescribe a treatment (e.g. lysine)6 have generated the kind of pushback often greeting such suggestions.
Nevertheless, we have a responsibility to heed the evidence and recognize when inaction may serve our patients better than intervention. One example of this that is beginning to gain some attention in veterinary medicine is subclinical or asymptomatic bacteriuria (AB).7 This is most simply defined as the presence of bacteria in urine without clinical signs compatible with a urinary tract infection (UTI).8–10 The definition of AB also may include a threshold quantity of bacteria grown on culture and repeated positive urine cultures to distinguish AB from transient bacteriuria and contamination of the urine sample.11,12
Are antibiotics needed?
In humans, the presence of bacteria without symptoms of UTI is quite common, though the prevalence varies with sex, age, and many other factors. Less than five percent of healthy, pre-menopausal women have AB, whereas 100 percent of people with chronic indwelling urinary catheters will have bacteriuria even when no symptoms of UTI are present. Prevalence is higher in the elderly, diabetics, and people with some other causes of immunocompromise.8,12
Despite this high prevalence, there is substantial research showing most people with AB do not benefit from antibiotic therapy.8,12–14 Even in diabetics, the elderly, and other individuals with potentially compromised immune function, AB does not seem to increase the risk of negative outcomes, and treatment with antibiotics provides no benefit and may even cause harm.12,14 Antibiotic treatment for humans with AB appears to be beneficial for only a very limited set of circumstances, such as in pregnancy and prior to transurethral resection surgery.11
Clinical practice guidelines for physicians recommend against screening and treatment for AB in most patient populations.11,12 Despite this, many physicians still prescribe antibiotics when they diagnose AB, particularly if pyuria or other findings are present that they believe indicate UTI even when the evidence does not support this practice. Education programs have been employed to reduce this inappropriate antibiotic use because it can increase patient morbidity and antibiotic resistance.8
It is less clear how common AB is in dogs and cats. Studies have found highly variable prevalence ranging from 28 percent to less than one percent of samples in cats15–20 and from 25 percent to zero percent of samples in dogs.9,10,21 The occurrence of AB appears to vary with many factors, including species, sex, age, body condition score (BCS), and presence of potentially predisposing diseases.7,10,15,17–19,21,22 Morbidly obese dogs, for example, appear more likely to have AB than dogs with less extreme body condition scores.21 Females are often reported to have AB more frequently than males.17,23
Interestingly, some studies have failed to find any association between potentially immunosuppressive drug treatment and AB, even though such medications have been reported to increase the risk of urinary tract infections.20,24–26 An increased risk in the presence of chronic kidney disease (CKD) has been seen in some reports, but not others.9,17
Unfortunately, most of the studies in veterinary patients have evaluated small numbers of patients, and they have varied methods and numerous limitations, which makes it challenging to compare studies or have much confidence in the results. Sufficient detail is lacking to clearly identify associations between specific patient characteristics and the prevalence and risk of AB. This makes it more difficult to challenge the reflexive urge many of us have to treat bacteriuria whenever we see it, despite the strong evidence in humans this may not always be best for the patient.
Is AB a predictor?
The limited veterinary evidence available does suggest AB is not likely to be a predictor or cause of subsequent disease.10,19 However, this conclusion must be viewed as tentative, given the strength of the evidence. The most recent guideline from the International Society for Companion Animal Infectious Diseases (ISCAID) offers the following recommendation:27 “Treatment may not be necessary in animals that have no clinical signs of UTI and no evidence of UTI based on examination of urine sediment. In some circumstances, treatment may be considered if there is concern there is a particularly high risk of ascending or systemic infection (e.g. immunocompromised patients, patients with underlying renal disease) or that the bladder may be a focus of extra-urinary infection.”
This is necessarily a far more tentative recommendation than guidelines for physicians due to the paucity of high-quality research evidence. Nevertheless, it reflects a growing awareness that treatment of AB is likely to be unnecessary in at least some veterinary patients and, as in humans, it may lead to increased antibiotic resistance and poorer clinical outcomes.
There also is research in humans showing that colonization of the urinary tract with nonvirulent bacteria can protect against more virulent and more antibiotic-resistant varieties. Such bacteria have been used clinically to reduce the risk of symptomatic UTI and more serious sequelae, such as pyelonephritis.12,28 AB was once considered a probable cause of pyelonephritis, but it is now recognized as benign or even a potentially protective condition.12
Research has been conducted to evaluate this potential prophylactic use of nonpathogenic organisms in dogs.29–31 In one study, instillation into dogs of an E. coli strain obtained from an individual with AB appeared to have no significant risks, and it may have been effective in treating and preventing some naturally occurring UTIs. The study was small and uncontrolled, so further research will be needed to confirm the safety and efficacy of this practice.
In the absence of conclusive evidence for veterinary species, individual clinicians must decide how to manage apparent cases of bacteriuria. While extrapolation from human medicine is not always reliable, it is a common starting point for making clinical decisions in veterinary patients. In cases when bacteriuria is identified and when there are no apparent clinical signs of UTI and no special circumstances (such as advanced age, immunosuppressive disease, or medical treatment, etc.), it is reasonable for veterinarians to choose not to provide antibiotic therapy. We must, of course, explain to clients the reasoning for this choice—including the goal of avoiding harm from unnecessary treatment—in the form of medication side effects and potentially more dangerous and drug-resistant UTIs.
When treating AB or uncomplicated UTI, we also should bear in mind that three to five days of treatment is the standard in human medicine.32–34 Though again the evidence is not yet conclusive in veterinary patients,35 it is likely that longer treatment only increases complications and reduces compliance without improving outcomes for our patients.
Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News.
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2 McKenzie BA. Veterinary clinical decision-making: Cognitive biases, external constraints, and strategies for improvement. J Am Vet Med Assoc. 2014;244(3). doi:10.2460/javma.244.3.271
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6 McKenzie B. Lysine: A therapeutic zombie? Vet Pract News. May 2018:26-28.
7 Senior DF. Subclinical Bacteriuria. Clin Br. November 2018:61-64.
8 Flokas ME, Andreatos N, Alevizakos M, Kalbasi A, Onur P, Mylonakis E. Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2017;4(4):ofx207. doi:10.1093/ofid/ofx207
9 Foster JD, Krishnan H, Cole S. Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease. J Am Vet Med Assoc. 2018;252(10):1257-1262. doi:10.2460/javma.252.10.1257
10 Wan SY, Hartmann FA, Jooss MK, Viviano KR. Prevalence and clinical outcome of subclinical bacteriuria in female dogs. J Am Vet Med Assoc. 2014;245(1):106-112. doi:10.2460/javma.245.1.106
11 Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005;40(5):643-654. doi:10.1086/427507
12 Nicolle LE. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria. Pathog (Basel, Switzerland). 2016;5(2). doi:10.3390/pathogens5020038
13 Bigotte Vieira M, Alves M, Costa J, Vaz-Carneiro A. Análise da Revisão Cochrane: Antibióticos Destinados ao Tratamento da Bacteriúria Assintomática. Cochrane Database Syst Rev. 2015;4:CD009534. Acta Med Port. 2018;31(2):76. doi:10.20344/amp.10077
14 Köves B, Cai T, Veeratterapillay R, et al. Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel. Eur Urol. 2017;72(6):865-868. doi:10.1016/j.eururo.2017.07.014
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17 Puchot ML, Cook AK, Pohlit C. Subclinical bacteriuria in cats: prevalence, findings on contemporaneous urinalyses and clinical risk factors. J Feline Med Surg. 2017;19(12):1238-1244. doi:10.1177/1098612X16688806
18 Eggertsdóttir A V, Sævik BK, Halvorsen I, Sørum H. Occurrence of Occult Bacteriuria in Healthy Cats. J Feline Med Surg. 2011;13(10):800-803. doi:10.1016/j.jfms.2011.07.004
19 White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C. Subclinical Bacteriuria in Older Cats and its Association with Survival. J Vet Intern Med. 2016;30(6):1824-1829. doi:10.1111/jvim.14598
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24 Simpson AC, Schissler JR, Rosychuk RAW, Moore AR. The frequency of urinary tract infection and subclinical bacteriuria in dogs with allergic dermatitis treated with oclacitinib: a prospective study. Vet Dermatol. 2017;28(5):485-e113. doi:10.1111/vde.12450
25 Torres SMF, Diaz SF, Nogueira SA, et al. Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment. J Am Vet Med Assoc. 2005;227(2):239-243. http://www.ncbi.nlm.nih.gov/pubmed/16047659. Accessed January 20, 2019.
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29 Thompson MF, Schembri MA, Mills PC, Trott DJ. A modified three-dose protocol for colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972. Vet Microbiol. 2012;158(3-4):446-450. doi:10.1016/j.vetmic.2012.03.012
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31 Segev G, Sykes JE, Klumpp DJ, et al. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI. J Vet Intern Med. 2018;32(1):267-273. doi:10.1111/jvim.14851
32 Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257
33 Kang C-I, Kim J, Park DW, et al. Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired Urinary Tract Infections. Infect Chemother. 2018;50(1):67. doi:10.3947/ic.2018.50.1.67
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