Feline Lower Urinary Tract Disease

Antibiotic Use in Feline Lower Urinary Tract Disease

Feline lower urinary tract disease may be caused by a variety of conditions. Although it can be challenging, it is important to distinguish between these conditions so that appropriate treatment is given and antimicrobial drugs are used judiciously.

Judicious use of antimicrobial drugs involves the dual goals of eradicating infection while avoiding development of antimicrobial resistance.

Judicious use of antimicrobial drugs encompasses:

  • Using an antibiotic only when indicated.
  • Choosing a cost-effective antibiotic agent that provides appropriate coverage for the diagnosis that is suspected.
  • Prescribing the optimal dose and duration of the antibiotic.

Learning Outcomes

This module describes a common scenario that clinicians may have to navigate when treating a cat with lower urinary tract signs. By the end of the module, you will learn the following:

  1. Factors that need to be considered when deciding to use antibiotic therapy in cats with lower urinary tract signs (for example, diagnosis, dose, frequency, and effective monitoring).
  2. When and when not to use antibiotics to treat feline lower urinary tract disease.
  3. The importance of bacterial culture results in the selection of an antibiotic.
  4. Empiric antibiotic therapy for feline lower urinary tract disease and when and how to use it.

Introduction

You have recently graduated from veterinary school and are an associate in a small animal practice. Your boss, having a new employee, has decided to take a vacation, leaving you in charge of the clinic while she is away. Jan, a new client who has recently moved to the area, has made an appointment to see you today.

Initial case presentation:

Nemo is a four-year-old, neutered male, domestic long-haired cat.

History: Nemo comes to your animal hospital with a two-day history of inappropriate urination outside of his litter box, and pollakiuria (frequent urination). The owner is very concerned because although she loves Nemo, she simply cannot tolerate a cat that urinates in inappropriate locations and not in the litter box.

Behavioral vs. Medical Periuria

In reference to cats with lower urinary tract signs, the three most important questions veterinarians need to ask to differentiate medical from behavioral inappropriate urination are urine volume, urine frequency and urine locations (what, how and where; table).

Table showing characteristics of normal urination versus behavioral or medical periuria

Because you know how important a good history is, you decide to ask Jan some more questions. Which question would you ask?

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Now it's time to Check Your Understanding of Which Questions to Ask.

Physical Examination

Physical examination of Nemo reveals the following:

  • Body Condition Score: 7/9 (overweight)
  • Weight: 13.0 lbs (5.9 kgs)
  • Rectal temperature: 102.5° F
  • The urinary bladder is small and when palpated Nemo postures and urinates approximately 3mls of urine on the examination table.
  • All other body systems are within normal limits.

Narrowing your differentials

Your physical examination has provided clues to Nemo’s problems. Based on your history and clinical exam findings, how would you localize the disease?

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Now it's time to Check Your Understanding of Localized Disease.

Now that we have localized the disease to the lower urinary tract, which diagnostic tests should you perform? 

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Now it's time to Check Your Understanding of Diagnostic Tests.

Diagnostic Tests

Selection of diagnostic tests is not an exact science. Knowing the prevalence of diseases associated with clinical signs and patient signalment can help to select tests likely to have the highest diagnostic utility. For example, the complete blood count (CBC) is a good screening test for overall health but it provides minimal diagnostic utility as to the cause of the lower urinary tract signs. Even for cats with bacterial infection of the bladder, CBC results are often unremarkable; however, acute kidney infection is usually associated with leukocytosis. A serum chemistry profile will evaluate internal organ function but, even if abnormal results are detected, they are rarely helpful in explaining lower urinary tract signs. Although both the CBC and serum chemistry profile are very good screening tests, Nemo’s problem appears to be localized to the lower urinary tract. To rule out the most common diseases, Jan’s money would be best directed toward a urinalysis and medical imaging of the lower urinary tract. 

You explain to Jan that a urinalysis and radiographs will be the most important tests to help identify what is the underlying source of Nemo’s problem. The urinalysis will identify the presence of blood, crystals, abnormal cells, or bacteria. The abdominal radiographs will help you look for urinary calculi, although some calculi may be radiolucent (not detectable on radiographs).

Jan agrees and consents to the urinalysis and abdominal radiographs.

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Now it's time to Check Your Understanding of Urine Collection.

 

Sample Collection

An important tool for any patient showing signs of a urinary tract disease is the urinalysis. This requires the collection of a urine sample. There are several methods for collecting urine, and each has advantages and disadvantages. For patients you suspect have a urinary tract infection, you should place a high priority on a technique that will obtain a sample with the least amount of contamination that can be used for bacterial culture.

Cystocentesis

Removal of urine from the bladder via cystocentesis guided by a firm hold on the bladder.

Cystocentesis following palpation

Cystocentesis following palpation

ultrasound-guided cystocentesis stabilization of bladder

Cystocentesis following ultrasound-guided stabilization of bladder

 

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Now it's time to Check Your Understanding of Antibiotic Prescription.

Sample problems

Nemo decides that he does not want to cooperate with your collection of a urine sample. After several attempts to isolate his urinary bladder, you come to the conclusion that his bladder is too small and Nemo appears too uncomfortable. When you explain to Jan that you cannot get a sample, she responds, “Well, just give me some antibiotics then so I can start giving them to Nemo in the meantime.”

Getting a sample

You explain to Jan that although Nemo could have an infection, there are many other diseases that cause similar signs (for example, calculi, neoplasia, etc.). Without knowing what the problems is, prescribing a medication such as an antibiotic could lead to antibiotic resistance and would also just be wasting her money. You tell Jan that you will be able to give Nemo some pain medication to keep him comfortable until a urine sample can be obtained.

Jan agrees to leave Nemo with you so you can get the needed samples. You give Nemo buprenorphine to help keep him comfortable. Later that day you successfully obtain a urine sample via an ultrasound-guided cystocentesis. During the urine collection, you note that although the urinary bladder appears thickened, you do not notice any unusual masses or growths.

Results

 

Feline Lateral radiograph

Feline lateral radiograph

Urinalysis

Usgr 1.040
pH 6.5
Color Lt Yellow
Glucose Neg
Bilirubin Neg
Ketones Neg
Occult Blood Neg
Protein +2
RBC 51−100/HPF
WBC 3−5/HPF
Bacteria None seen
Casts None seen
Crystals None seen

 

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Now it's time to Check Your Understanding of Treatment Options for FLUTD.

What To Do Next?

Based on your physical examination, patient history, and laboratory findings, you feel strongly that this is an inflammatory process such as Feline Lower Urinary Tract Disease (FLUTD); however, Jan is pushing for antibiotics just in case there is an infection that is not obvious from the UA. 

More diagnostic testing

You tell Jan that young male cats are unlikely to have UTIs. However, a urine culture could be used to rule out infection if she feels strongly about the need for antibiotics. You think that the best way to proceed is to culture the urine to see if an antibiotic is warranted.

She responds by saying, “If you’re going to give me an antibiotic anyway, why waste my money and culture the urine? Besides, I'll be lucky if I can even get Nemo to take pills.”

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Now it's time to Check Your Understanding of Appropriate Response.

Diagnostic vs. Therapeutic Urine Cultures

What are diagnostic urine cultures?

  • Quantitative urine cultures before initiating antibiotic therapy is considered to be the gold standard for diagnosis of bacterial urinary tract infections (UTI).
  • Diagnostic urine cultures provide accurate identification of specific bacterial species and aid in the selection of antibiotics. It also facilitates differentiation between recurrent UTIs caused by relapses (the same organism) or recurrent UTIs caused by reinfections with a new organism.
  • If a patient is currently being treated with an antibiotic, it should be discontinued for three to five days before diagnostic urine culture to minimize inhibition of bacterial growth.

What are therapeutic urine cultures?

  • Culture of urine at strategic times during antibiotic therapy (“therapeutic urine cultures”) is an effective method of assessing in vivo therapy. Therapeutic cultures are essential for determining why a patient may not be responding to appropriate treatment.
  • For patients with a high risk of morbidity and mortality (for example, prostatitis, pyelonephritis, immunosuppression, urinary tract obstruction), evaluation of urine culture and urinalysis three to five days after initiating therapy allows for verification of antibiotic effectiveness before the development of irreversible organ damage or systemic spread of disease. The same strategy should be considered when prescribing antibiotics with a high risk of toxicity.

Benefits of therapeutic urine cultures:

  1. Timely test of antibiotic efficacy
  2. Verification of proper antibiotic administration
  3. Early detection of bacterial resistance to antibiotics
  4. Timely detection of persistent infections
  5. Provision of justification for early discontinuation of potentially toxic antibiotics

Suggested times to culture urine to diagnose and monitor persistent urinary tract infections:

I. Diagnostic

  • Before administration of therapy

II. Therapeutic

  • 3 to 5 days after initiating therapy
  • Any time clinical signs of laboratory abnormalities recur during therapy
  • Before discontinuing therapy

Initial Treatment

Jan reluctantly agrees to the urine culture saying, “Well, I guess if that’s what we need to do. No offense doc, but I really don’t want to be in here for the same problem in another month!”

While waiting for urine culture results, you prescribe an analgesic to keep Nemo comfortable. You tell Jan that the urine culture and sensitivity should be available in two days. If Nemo stops producing urine or continues to be uncomfortable, she needs to bring him back in immediately! You explain that a blockage in the urinary tract is a life-threatening situation. In the meantime, you did not prescribe empiric antibiotic therapy.

Empiric antibiotic therapy is the use of an antibiotic when the etiologic agent has not been confirmed.

When is it okay to use empiric antibiotic therapy?

Empiric antibiotic therapy should only be started when depriving a patient of therapy (while waiting for urine culture and sensitivity results) may result in harm or worsening of the condition.

  • When the agent is not known, selection of the antibiotic should be based on the most likely agent to be found in that location. 
  • Antibiotic selection needs to be selected not only on the suspected agent, but also on the ability to obtain a therapeutic concentration at the site of infection. For most tissues, plasma concentration can be used to predict tissue concentration. However, areas with poor blood supply can be problematic (for example, abscesses). Lipid membranes can also affect drug profusion (for example, in CNS, eye, or prostate tissues). Some antibiotics reach high concentrations in the urine and are good choices for lower urinary tract infections. 

For current guidelines for empiric antibiotic therapy see the International Society for Companion Animal Infectious Diseases (ISCAID) website under Antimicrobial Guidelines:

Culture Results

Two days after sending Nemo home with analgesic therapy, you receive the results of the urine culture.

Culture, Urine

Test results: No growth after 48 hours.

Diagnosis

Feline Idiopathic Cystitis

Feline idiopathic cystitis (FIC)—also called interstitial cystitis—is the most common diagnosis in cats with lower urinary tract signs. FIC is a diagnosis of exclusion, meaning that the term FIC is used if all diagnostics fail to confirm the presence of another disease such as urinary stones. Cats suffering from FIC make frequent attempts to urinate, most likely as a result of bladder discomfort, and often are found to have blood in their urine. Signs of lower urinary tract disease in cats with nonobstructive FIC often resolve spontaneously within a couple of days regardless of treatment. Most treatments attempt to prevent subsequent recurrence of signs.

Stress seems to be an important factor in the development of FIC in cats. Possible sources of stress in a cat's life may include environmental changes, changes in food schedule, and changes in the number of animals in the household. Environmental enrichment and modification can reduce stress and decrease the severity and frequency of FIC episodes.

For more information see:

Cornell Feline Health Center: Feline Lower Urinary Tract Disease

Veterinary Partner: Idiopathic Cystitis in Cats

Treatment Plan

How would you like to proceed with treatment?

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Now it's time to Check Your Understanding of How to Proceed.

 

You explain to Jan your treatment plan for Nemo which includes Buprenorphine for pain relief, a diet change to canned food to increase Nemo’s water consumption, and using a product like Feliway while he adjusts to the move and the new house. You also recommend that she place an additional litter box in a different area of the house so Nemo can choose which location he is more comfortable with. Then you remind her that cats like clean litter boxes so she should clean all the boxes out at least once if not twice per day.

Jan says, “I don’t understand. Why am I not getting any antibiotics? Doesn’t Nemo have an infection?”

You tell her, “No, Nemo does not have an infection. Improper use of antibiotics has caused a huge problem recently with the development of antibiotic-resistant ‘super bugs.’ Using an antibiotic when it is not indicated can create resistant bacteria strains that are not easily treated and have the potential to be transmitted to other animals or even people.”

Jan says, “Is that like this MRSA superbug I’ve been hearing about? That sounds awful! I don’t want Nemo to get that and I certainly don’t want to get that myself!”

What is antimicrobial resistance?

  • Antimicrobial resistance occurs when microorganisms have or develop the ability to resist the action of an antimicrobial drug. In other words, antimicrobial resistance exists if targeted microorganisms can survive and reproduce in the presence (and dose) of an antimicrobial drug that used to prevent the survival and reproduction of those microorganisms.
  • Antimicrobial resistance can occur through intrinsic or acquired mechanisms (see the Microbiology Module for more details). Clinical considerations include:
  1. Even if an effective antimicrobial drug is used, rarely, if ever, will 100% of the microorganisms be killed during the course of treatment. The few surviving and potentially resistant microorganisms could then transfer their genetic material to their offspring or other unrelated microorganisms.
  2. Bacteria that were at one time susceptible to an antibiotic can acquire resistance through mutation of their genetic material or by acquiring transferred pieces of DNA from other bacteria, of the same or different species, that code for the resistance properties. The DNA that codes for resistance can be grouped in a single easily transferable package, such as plasmids. This means that bacteria can become resistant to many antimicrobial agents because of the transfer of one piece of DNA.

Examples of resistant strains of bacteria that have developed:

  • Methicillin Resistant Staphylococcus aureus (MRSA)
  • Multidrug Resistant Tuberculosis (MDR TB)—TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin
  • Extremely Drug Resistant Tuberculosis (EDR TB)—TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (amikacin, kanamycin, or capreomycin)
  • Staphylococcus pseudintermedius
  • Fluoroquinolone-resistant Campylobacter
  • Multi Drug Resistant Salmonella
  • Vancomycin Resistant Enterococci (VRE)

Follow-up

A few days after Nemo’s appointment, you call for an update. Jan reports that Nemo is doing wonderfully and has gone back to using his litter box. She can tell that he feels a whole lot better and is adjusting well to the diet change.

Jan thanks you for the wonderful care you gave Nemo. You remind Jan that she can discontinue the buprenorphine once it is finished, but everything else prescribed is something she should continue doing with Nemo to prevent recurrence of the idiopathic cystitis.

Module Summary 

  • In a feline patient with lower urinary tract signs, it is important to differentiate medical versus behavioral inappropriate urination.
  • Signs indicating medical inappropriate urination include urination on various locations and horizontal surfaces, hematuria being more likely, and more likely in a household with fewer cats.
  • Diagnostic testing including urinalysis and urine culture via cystocentesis, abdominal radiographs, and abdominal ultrasound are also very important to differentiate the causes for lower urinary tract signs such as infection, stones, and neoplasia.
  • Feline Idiopathic Cystitis (FIC) is diagnosed when all the above testing is negative for an alternative cause.
  • Treatment for FIC includes providing pain medication, reducing stress, changing diet and increasing water consumption, increasing availability to litter boxes, and cleaning litter boxes at least once daily.

References 

    1. Osborne, C, J Lulich, J Kruger, et al. Analysis of 451,891 Canine Uroliths, Feline Uroliths, and Feline Urethral Plugs from 1981 to 2007: Perspectives from the Minnesota Urolith Center. Vet Clin North Am Small Anim Pract 2009 Jan;39(1):183-97. doi: 10.1016/j.cvsm.2008.09.011.
    2. Lulich, J, and C Osborne. Urine culture as a test for cure: why, when, and how? Vet Clin North Am Small Anim Pract 2004 Jul;34(4):1027-41, viii. doi: 10.1016/j.cvsm.2004.03.005.
    3. Lekcharoensuk, C, Osborne C, Lulich J. Epidemiologic study of risk factors for lower urinary tract diseases in cats. J Am Vet Med Assoc 2001 May 1;218(9):1429-35.  doi: 10.2460/javma.2001.218.1429.
    4. Weese JS, Blondeau J, Boothe D, et al. International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J. 2019 May;247:8-25. doi: 10.1016/j.tvjl.2019.02.008.