Feline Urinary Tract Disease

Antibiotic Use in Feline Urinary Tract Disease

Judicious use of antimicrobials encompasses the dual goals of eradicating of infection while avoiding development of antimicrobial resistance.

Judicious use of antimicrobials encompasses:

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

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.

Questions to Ask

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).

Behavioral Periuria Medical Periuria
Urine Frequency
Consistent Locations in Vertical surfaces Variable Locations in Horizontal surfaces
Hematuria
Unlikely Likely
Environment
Multicat Household Fewer Cat Household

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 reveals the following:

  • Body Condition Score—7/9 (overweight).
  • Weight 13.0 lbs (5.9 kgs).
  • Rectal temperature is 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, but 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 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 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 X-rays.

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 infection. The abdominal radiographs will look for urinary calculi.

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 and Sample Problems

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 can not get a sample, she responds, “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. 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 (Buprenex , 0.01mg/kg, SC) 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 appeared thickened, you did 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.

Mineral composition of 11,174 feline uroliths evaluated at the MUC, 2007.

Predominant Mineral Type Number of Uroliths %
Magnesium ammonium phosphate 6H2O 5,432 48.6
Magnesium hydrogen phosphate 3H2O 7 0.06
Magnesium phosphate hydrate 42 0.38
Calcium oxalate 4,553 40.8
Calcium phosphate 30 0.3
Purines 523 4.9
Xanthine 27 <0.1
Cystine 12 <0.1
Silica 8 <0.1
Other 10 <0.1
Mixed* 81 0.7
Compound** 356 3.2
Matrix*** 93 .08
Date 2007 11,174 100

*Analyzed by polarizing light microscopy or infrared spectroscopy.

**Uroliths did not contain at least 70% of mineral type listed; no nucleus or shell detected.

***Uroliths contained an identifiable nucleus and one or more surrounding layers of a different mineral type.

What To Do Next?

Based on your physical examination, patient history, and laboratory findings, you are unsure whether Nemo may have a bladder infection or some other underlying inflammatory process such as idiopathic Feline Lower Urinary Tract Disease (iFLUTD).

Culture

You tell Jan that the lab findings indicate either a urinary tract infection or inflammation. You think that the best way to proceed is to culture the urine and then prescribe an antibiotic if warranted based on culture results.

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 of recurrent UTIs caused by relapses from recurrent UTIs caused by reinfections.
  • 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 therapy. Therapeutic cultures are essential for determining why a patient may not be responding to treatment.
  • For patients with a high risk of morbidity and mortality (e.g., 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

III. Surveillance

  • 7 to 14 days after stopping therapy
  • 1 to 2 months after stopping therapy
  • 3 to 6 months after stopping therapy
  • Any time clinical signs recur

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!”

Initial Treatment:

While waiting for urine culture results, you prescribe an analgesic (Buprenorphine, 0.01mg/kg q 8 to 12 hours between the cheek and gums) 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.

Empiric antibiotic therapy is the use of an appropriate antibiotic when the exact etiologic agent is unknown.

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 (abscesses). Lipid membranes can also affect drug profusion (CNS, eye, prostate).

Guidelines for Empiric Antibiotic Therapy

Infection

Bacteria

Antimicrobic Options

Urinary tract infection

E. coli, Proteus, Pseudomonas, Enterobacter, Pasteurella (more in cats), Staphylococcus, Streptococcus, and Enterococcus

First choices:

  • Amoxicillin + clavulanate; cephalosporins

Options:

  • Sulfonamides; fluoroquinolones; tetracyclines

In uncomplicated, never before treated, lower urinary tract infections in immunocompetent animals, amoxicillin + clavulanate is very effective against the most common pathogens (sulphonamides work better against E. coli)

Prostatitis

E. coli, Staphylococcus, Klebsiella, Proteus, and Mycoplasma canis

First choices:

  • Sulfonamides; enrofloxacin

Options:

  • Doxycycline; erythromycin (gram-positives only)

Pneumonia

Usually mixed with E. coli in complicated cases

First choices:

  • Amoxicillin + clavulanate; fluoroquinolones

Options:

  • Cephalosporins (do not effectively cross the blood-bronchus barrier; work for pneumonia)
  • Aminoglycosides (do not effectively cross the blood-bronchus barrier)
  • Sulphonamides
  • Clindamycin (Streptococcus)

Sepsis

Dogs: Staphylococcus, E. coli, Streptococcus, Salmonella, Proteus

Cats: E. coli, Klebsiella, Salmonella, anaerobes

 

First choices:

  • Amoxicillin + clavulanate + fluoroquinolone
  • Cephalosporin + fluoroquinolone

Options:

  • Second or third generation cephalosporins
  • Aminoglycosides (gram-negative)
  • Clindamycin (anaerobes)

Empiric Antibiotic Therapy, World Small Animal Veterinary Association World Congress Proceedings, 2009. Helio Autran de Morais, DVM, PhD, AVCIM; Oregon State University

Culture Results

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.

Diagnoses of LUTD in Cats (No. [%])

in reports of three studies (1980−1997; 1982-1985; 1993−1995)

Diagnoses* 1980-1997 study 1982-1985 study 1993-1995 study
Urolith 2,209 (10) 62 (44) 16 (15)
Urocystolith 935 (4) 32 (23) 16 (15)
Urethral plug or urethrolith 1,224 (5) 30 (21) NA
Urocystolith, urethral plug, or urethrolith 50 (0.2) 0 (0) NA
Urethral obstruction 4,405 (19) 51 (36) NA
Infection 2,789 (12) 4 (3) 1 (1)
Undefined 1,993 (9) 0 (0) 0 (0)
Bacterial 784 (3) 2 (2) 1 (1)
Viral 13 (0.1) 0 (0) 0 (0)
Trauma 409 (2) 0 (0) 0 (0)
Neurogenic causes 53 (0.2) 0 (0) 0 (0)
Postsurgical iatrogenic injuries 126 (0.6) 0 (0) 0 (0)
Congenital defects 152 (0.7) 0 (0) 12 (11)
Neoplasia 78 (0.3) 0 (0) 2 (2)
Urinary incontinence 892 (4) 0 (0) 0 (0)
Chemical and drug-induced inflammation 2 (<0.1) 0 (0) 0 (0)
Idiopathic 14,467 (63) 77 (55) 80 (73)
Miscellaneous 544 (2) 0 (0) 0 (0)
Total 22,908 (100) 141 (100) 109 (100)

NA = Not applicable.

*More than one cause of LUTD was identified in some cats.

Diagnosis

1980−1997 study

1982−1985 study

1993−1995 study

Urolith

10%

44%

15%

Infection

12%

3%

1%

Neoplasia

0.3%

0%

2%

Idiopathic

63%

55%

73%

 

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, probably 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 weeks 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.

Cornell Feline Health Center: Feline Lower Urinary Tract Disease

Feline Idiopathic Cystitis
By Wendy C. Brooks, DVM, DABVP

Veterinary Partner: Idiopathic Cystitis in Cats

How To Proceed?

How would you like to proceed with treatment?

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

Treatment Plan

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 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 a microorganism develops the ability to resist the action of an antimicrobial. Basically, the microorganism develops the ability to survive and reproduce in the presence (and dose) of an antimicrobial that used to prevent these actions.
  • Antimicrobial resistance could occur through:
  1. “Selection pressure”—even if an effective antimicrobial is used, rarely, if ever, will 100% of the organisms be killed during the course of treatment. The few surviving and potentially resistant organisms could then transfer their genetic material to offspring or other unrelated organisms.
  2. Mutations—bacteria that were at one time susceptible to an antibiotic can acquire resistance through mutation of their genetic material or by acquiring pieces of DNA that code for the resistance properties from other bacteria. The DNA that codes for resistance can be grouped in a single easily transferable package. 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)

Update

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 (Antibiotic Use in Feline Urinary Tract Disease)

  • 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 with all the above testing is negative for an alternative cause.
  • Treatment for FIC includes pain medication, reducing stress, diet change and increasing water consumption, increasing availability to litter boxes, and to clean litter boxes at least once daily.

References (Antibiotic Use in Feline Urinary Tract Disease)

    1. Osborne, C, J Lulich, J Kruger, et al. 2009. Analysis of 451,891 Canine Uroliths, Feline Uroliths, and Feline Urethral Plugs from 1981 to 2007: Perspectives from the Minnesota Urolith Center. The Veterinary clinics of North America. Small Animal Practice. 39(1):183.
    2. Lulich, J, and C Osborne. 2004 Urine culture as a test for cure: why, when, and how? The Veterinary clinics of North America. Small Animal Practice. 34(4):1027.
    3. Lekcharoensuk, C, C Osborne, J Lulich. 2001. Epidemiologic study of risk factors for lower urinary tract diseases in cats. Journal of the American Veterinary Medical Association. 218(9):1429-1435.