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ISCAID Guidelines & management of bacterial urinary tract infections in dogs & cats: Part I | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary continuing education podcast, we’ll review the latest guidelines for a condition we see just about every day in the vet hospital – urinary tract infections (UTIs). This is based off the most current International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats . This is a 2-part podcast, so tune in next week for Part 2!

I’m sure that, like me, you all have your own way of working things up and treating UTIs on a case by case basis. But with antimicrobial resistance on the rise in both human and veterinary medicine, we can benefit from guidelines such as these to help modify our practices and hopefully limit any overuse of antimicrobials. Keep in mind that these guidelines, while meant to help us with the majority of our cases, are by no means meant to be the only way to practice. There are so many considerations in each case that we will be reviewing – like has the animal already had recurrent infections? Are there stones present that can be fostering bacteria? Are there rules in place for prophylactic and empiric use of antibiotics? So, we will be summarizing these rather long guidelines in hopes of streamlining our diagnostic approach and treatment of various urinary tract infections in the cat and dog.

These guidelines are the latest updated revision of similar guidelines put out by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Disease. It’s likely that these guidelines will continue to be adjusted over time as newer high-level studies are conducted in regards to veterinary antimicrobial usage for urinary tract infections. At present, these guidelines reflect information obtained from both human and veterinary studies and anecdotal information.

Sporadic Bacterial Infections
First, we will look at what we know as the typical bladder infection – sometimes called the “uncomplicated UTI”- which is referred to in these guidelines as “sporadic bacterial cystitis.” These guidelines stray away from using terms such as “complicated” or “uncomplicated” to describe UTI’s, because these terms lack clear definitions in the veterinary world. Sporadic bacterial cystitis is defined as a UTI in animals without predisposing anatomic abnormalities or comorbidities, in non-pregnant females or neutered males, that have had less than 3 episodes of cystitis within 12 months.

Dogs most commonly present with the clinical signs of pollakiuria, dysuria, or stranguria. Bacterial cystitis in cats is not commonly encountered as most felines suffer instead from a sterile process called sterile feline idiopathic cystitis. Cats can also develop urolithiasis, but it’s usually without a bacterial component. True bacterial cystitis in cats is uncommon and more likely to be seen in older cats due to the presence of other co-morbidities.

All animals presenting with signs of a lower UTI should be offered a urinalysis that includes a urine dipstick, USG, and a urine sediment review, as well as an aerobic urine culture that is preferably obtained via cystocentesis. When available, ultrasound should be used for cystocentesis because this modality allows for a sneak-peak at any bladder wall abnormalities, kidney abnormalities, and stones can be screened for. If cystocentesis is not possible, voided samples can be processed for culture as a last resort. Voided urine must be refrigerated immediately after collection and/or processed for culture within hours after collection. Voided samples will produce false positives so it is important that these samples be processed by a veterinary diagnostic lab for interpretation to determine which bacteria are the most pathogenic. Urine collected from newly placed urinary catheters should also be handled in this fashion. Urine collected via cystocentesis should be stored under refrigerated conditions and processed for culture within 24 hours after collection. Let’s harp on that point for a moment. The recommendation is for urine to be PROCESSED for culture within 24 hours after it is collected. This is because bacterial viability decreases while urine is stored outside the body. So if you are collecting urine for culture, keep in mind that a sample collected on a Friday or on a Saturday, may not be initially processed within this timeframe. It’s always best to confer with your local lab to streamline your hospital’s submission process, ensuring that all samples arrive at the destination laboratory in a timely fashion and under the most ideal shipping conditions for each sample.

Treatment of sporadic bacterial cystitis has two parts: alleviation of pain and resolution of infection. For pain, the guidelines recommend using analgesics such as NSAIDS. NOTE: VETGirl cautions you to first check kidney and liver values prior to prescribing an NSAID, always use caution in cats, and follow FDA-approved drug dosages for the medication. While you’re waiting for urine culture results to become available, it is reasonable to treat suspected bacterial cystitis with empiric antimicrobial therapy in dogs. However, treatment with analgesics alone is also feasible until culture results are available. In cats, since the likelihood of true bacterial cystitis is uncommon, it is reasonable to withhold antimicrobial therapy until culture results are available. Plus, cat owners often can’t medicate anyway, so let’s think about client compliance here! Amoxicillin is a good first-line empiric antimicrobial for this condition. If amoxicillin isn’t readily available, you can consider amoxicillin with clavulanic acid. TMS is another reasonable first-line drug, but it can have negative side effects, albeit rare. Bear in mind, the negative side effects seen with TMS occur at higher doses for longer periods of time than treatment of a simple UTI. Owner compliance poses a special circumstance that may warrant straying from these first-line recommendations. A once daily 3rd generation cephalosporin may be easier for your clients to remember and to administer compared to twice daily amoxicillin/clavulanic acid. Surprisingly, the dosing recommendations for sporadic bacterial cystitis is only 3-5 days (not the 10-14 days we have been doing in years past!)!

Now there’s a bunch of case considerations to review that can throw a wrench into your well-laid-out plan. Let’s say your patient has not been exposed to many antimicrobials in their past. It’s reasonable to treat this patient with empiric therapy without performing a urine culture (although here at VETgirl, we do recommend at least offering this option to your clients). This doesn’t pertain to the cat; since they don’t typically have bacterial cystitis, cats should still only receive antimicrobials if urine cultures indicate the need. For another situation, let’s say that your patient’s culture results come back and suggest that the empiric antimicrobial you have them on demonstrates a resistance pattern, but your patient is actually clinically improving. It is absolutely reasonable to keep your patient on a full course of this antimicrobial and base your success or failure on whether you achieve complete resolution of clinical signs. Or the reverse – let’s say you have a patient on an empirically chosen antimicrobial that the culture results say should work, but your patient is failing to show clinical improvement. It’s time to switch to a different antimicrobial based on the initial culture results. Or what if you didn’t perform a culture in the first place? This is completely reasonable in animals that don’t have recurring UTIs but if your patient is not clinically improving within 48 hours after starting your empiric antimicrobial, it’s time to submit a urine culture before changing antimicrobials to obtain guided treatment recommendations, and also to start looking for co-morbidities that could be preventing the antimicrobial from clearing the infection. Follow-up urinalysis and urine cultures are not recommended after cessation of treatment for sporadic bacterial cystitis as long as clinical resolution has been reached. Yes, you heard that right. As long as clinical signs have resolved, with uncomplicated, sporadic UTIs, no need to culture post-antimicrobial therapy.

Last, these guidelines recommend against the use of intravesicular infusions of antimicrobials and anti-inflammatories due to lack of proven efficacy. We also don’t have robust data to make a recommendation in support of using adjunctive treatments such as cranberry extract, though it’s unlikely to harm the patient.

Recurrent bacterial cystitis
Recurrent bacterial cystitis is defined as three or more UTI’s within a 12-month period, or two or more UTI’s within a 6-month period; these can be relapses of the same infection or can be caused by different bacteria species. Identifying co-morbidities in these patients is important so that underlying causes for recurrent bacterial cystitis can be eliminated. Diagnosis includes a positive urine culture within the designated time period. Other diagnostics to perform in these cases include ultrasound, radiographs, contrast radiographs, and possibly cystoscopy. If urine cultures are negative for growth, but you really suspect bacterial cystitis is at play, bladder wall biopsies should be submitted for culture to identify bacterial infections that can be residing deep within the bladder wall. If the patient presents with reinfections from different pathogens, the clinician should look hard for other co-morbidities that can be predisposing the pet to UTIs. If the infection is a relapse or a persisting infection, the clinician should first ensure that the antimicrobial was used appropriately – check the drug’s susceptibility pattern, dose, interval, and be sure to inquire about the client compliance.

Again, treatment for recurrent bacterial cystitis has two parts: pain relief and treating the infection. While waiting on urine culture results, these patients should always receive the benefits of analgesics. Again, empiric antimicrobial therapy is reasonable while waiting on culture results to guide directed medical therapy. Antimicrobial selection should then be adjusted based on culture results and clinical signs. So, if your patient’s clinical signs are not improving on the antimicrobial you started while waiting on the culture results, this medication should be discontinued and a new antimicrobial started based on the culture results. If clinical signs are improving but the culture results suggest that the UTI is resistant to your chosen empiric antimicrobial, it is reasonable to continue with this drug until the pet has reached clinical resolution.

Just like with sporadic bacterial cystitis, a re-infection with a different pathogen (one that is new to the patient) can be treated with a short 3-5 day course of antimicrobials. A persistent or relapsing infection should be treated for 7-14 days. Infections involving the bladder wall should be treated with antimicrobials known to have good tissue penetration, but still following these rules of duration of treatment.

Now, when do we consider rechecking a urine culture with recurrent bacterial cystitis? In the middle of treatment to ensure our antimicrobials are working? After treatment to ensure we have cleared the infection? How far out from cessation of treatment is long enough? If your patient is receiving the short-course (3-5 days) of antimicrobial treatment, it doesn’t help the case to culture the urine during treatment. If your patient’s UTI falls into the longer (7-14 days) of treatment, then a urine culture at around 5-7 days is a reasonable consideration, but not mandatory. If this intra-treatment urine culture yields positive results, then the clinician should investigate client compliance and pursue further testing for co-morbidities that could be underlying causes for failure to respond to therapy. Simply changing the antimicrobial without further investigation is NOT recommended. If you wish to determine if the infection has cleared, it is reasonable to culture a urine sample 5-7 days after the end of antimicrobial therapy. Now, if this post-treatment culture shows positive growth, the clinician can investigate client compliance, but this persistent infection should be a trigger for referral to a specialist. The guidelines do not have recommendations yet regarding whether to use pulse therapy or other creative drug dosing schemes to help manage these difficult to clear infections. In women, sometimes daily doses of antimicrobials are used for these hard to clear infections, but studies in dogs and cats are lacking, so this is not a veterinary recommendation at this time.

Subclinical Bacteriuria
The term “subclinical bacteriuria” in these guidelines refers to pets that are clinically normal and symptom-free, but have bacteria present in their urine that is confirmed by culture on urine obtained via cystocentesis. This condition is not uncommon and has a higher incidence in animals with comorbidities such as diabetes mellitus. This condition is not as well studied in cats, though these guidelines report there is a confirmed incidence in cats ranging from 1-13%.

As part of our screening in various health conditions and in periodic health checks, we recommend performing a urinalysis. So, what do we do with the finding of bacteriuria in pets that have no symptoms consistent with UTIs? Human studies have found that untreated subclinical bacteriuria was unlikely to manifest into clinical bacteriuria. We do not have similar robust veterinary studies, but at this time, the recommendations are against treatment of subclinical bacteriuria unless you feel it is impacting comorbidities. Even if a culture is performed and the bacteria exhibits multidrug resistance, but the patient is asymptomatic, treatment is not recommended. Withholding treatment in these cases has anecdotally resulted in replacement of the multidrug resistant bacteria with susceptible organisms, which are then easier to treat. However, in animals with conditions such as diabetes mellitus, we often screen urine as part of a workup for the cause of diabetes dysregulation. If we find a subclinical bacteriuria in patients with diabetes mellitus or in paralyzed patients from spinal cord injuries, do we treat? The guidelines do not have a strong recommendation for these conditions. These are situations where we should use our clinical judgement and if we feel that the pet’s dysregulation could be attributed to a UTI or if we feel a paralyzed patient’s quality of life could possibly be improved from treating a suspected UTI, then we should proceed with a short-course (3-5days) of antimicrobials. If the clinician is concerned that their patient is high-risk for an ascending infection resulting in pyelonephritis, treatment is also reasonable, but we do not have data to prove what constitutes a patient as high-risk. If a positive culture in an asymptomatic patient grows a plaque-former (Corynebacterium urealyticum) or a urease-producer (Staph species), treatment is reasonable to prevent a challenging cystitis and perhaps struvite urolith formation with a 3-5 day course of antimicrobials. There is no contraindication to using adjunctive treatments such as cranberry extracts or probiotics, but there is no evidence to suggest they are beneficial. There is also no recommendation to periodically recheck urine from animals with subclinical bacterial cystitis, as long as they remain asymptomatic.

Upper Urinary Tract Infections
Diagnosing upper urinary tract infections (pyelonephritis) proves challenging in cats and dogs. We reach this diagnosis with a combination of positive urine cultures, clinical signs such as fever, PU/PD or oliguria/anuria, renal or abdominal palpation, and bloodwork documenting renal value disturbances and a neutrophilia with or without a left shift. Abdominal ultrasound may show renal pelvic dilation, but this finding can be misleading as normal animals or animals on IV fluid therapy can have renal pelvic dilation. Lab values such a serum creatinine and serum symmetric dimethylarginine (SDMA) are indicators of GFR, so they will indicate renal injury but are not specific for pyelonephritis. If a culture from urine obtained by cystocentesis is negative, a pyelocentesis can be considered. If the patient is febrile and/or immunosuppressed, the recommendation is to submit blood cultures at the same time as urine cultures. For treating pyelonephritis, it is important to consider antimicrobials with good tissue penetration as opposed to antimicrobials with only good concentration in the urine. Be sure you make this distinction when reading the antimicrobial susceptibilities on your culture results. Patients with negative urine cultures should be screened for Leptospirosis by PCR and serologic testing.

Although it may be reasonable in cases of bacterial cystitis to withhold antimicrobials while waiting on culture results, cases of suspected pyelonephritis should be treated immediately. Empiric antimicrobial selection should be aimed at treating Enterobacter species based on regional susceptibility patterns provided by your local laboratory. Reasonable first-line medications for pyelonephritis include fluoroquinolones, cefpodoxime, and cefotazime. If the patient has had a relatively recent urine culture in the past few months, empiric antimicrobial selection should be based on these culture results, keeping in mind that tissue concentrations of the listed antimicrobials are more important than the urine concentrations. If the patient is eating and otherwise well, oral antimicrobials can be used. Whereas, if the patient is dehydrated or not eating, it is best to start with intravenous administration of antimicrobials. When culture results are available, the patient can be de-escalated from combination therapy. Any antimicrobials the patient is on that produce a resistance pattern should be discontinued. If the patient is on an antimicrobial that has a favorable susceptibility result, but the pet is failing to improve clinically, it is reasonable to switch antimicrobials to another listed as being susceptible. If the patient was started on an antimicrobial that proves to have a resistance pattern, but the pet is clinically improving, then it is reasonable to maintain the course, but it would also be just as reasonable to switch antimicrobials. The clinician has to cautiously interpret whether the patient is improving from other treatment modalities such as IV fluid therapy or electrolyte correction as opposed to attributing all clinical improvement to the antimicrobial. If the culture results show multidrug resistance, the clinician should consult with a veterinary specialist in the field of internal medicine, pharmacology, or microbiology. If the patient has been on appropriate antimicrobials for 72 hours and is failing to show clinical response and renal values are not improving, then the clinician should investigate further for a cause of renal injury other than pyelonephritis.

Based on human data, duration of treatment for acute pyelonephritis should be 10-14 days. The patient should be rechecked by a veterinarian 1-2 weeks after the antimicrobial course is completed. The pet should receive a full physical examination, have kidney values evaluated on bloodwork, and have a urine sample collected via cystocentesis for a urinalysis and aerobic culture. If the pet is clinically normal with a positive urine culture, the infection should be managed in the fashion of a “subclinical bacteriuria” and an investigation into comorbid conditions should occur.

When in doubt, make sure you are aware of the newest updates in management and treatment of UTIs in dogs and cats based off these ISCAID guidelines! Check out next week for Part 2.

Abbreviations:
UTI – Urinary tract infection
SDMA – serum symmetric dimethylarginine
DM – Diabetes Mellitus
IV – intravenous

References:
International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats . The Veterinary Journal 2019;247:8-25

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