9/30/2013. Challenging Urinary Tract Infections. Maureen Finke, DVM, DACVIM

Transcription

1 1 2 Challenging Urinary Tract Infections Maureen Finke, DVM, DACVIM How Common are UTIs? Dogs 5-27% of dogs will develop UTI during their lifetime Female > Male Cats Rarely in cats < 10 years ( < 2%) More common in older cats over 10 years What is a UTI? A breach in host defense mechanisms that allows infectious organisms to adhere and colonize the urinary tract. Multifactorial causes Bacterial Factors Number of bacteria Virulence of bacteria Host Factors Anatomy Micturition status Immune status Where are the bacteria coming from? Ascending infections via the urethra Skin flora around the vulva/prepuce GI flora from fecal contamination Most common isolates from urine E. coli (40%) Gram + cocci (30) Hematogenous infection uncommon but usually due to bacteremia Bacterial virulence Many E. coli, Klebsiella, Proteus, Pseudomonas spp are opportunistic Pathogenicity depends on presence of virulence factors Adhesins, Fimbriae Toxins Bacterial resistance Bacterial populations change in response to pressure from antibiotics. Alterations in bacterial DNA Genomic DNA and chromosomal mutations Plasmids genes for virulence and resistance 1

2 9 10 Host Defenses Normal Micturition storage and voiding Anatomy Mucosal Defense Antimicrobial properties of urine Normal immune system Host Defenses Storage and Volume Normal urine flow and complete voiding number of ascending bacteria adherence time Decreased frequency of urination UMN bladder (IVDD) Owner work schedule Urinary retention LMN bladder, atony Dysautonomia, dyssynergia 11 Host Defenses Anatomy Urethral sphincter creates a high pressure zone bacterial migration to bladder USMI Ureteral peristalsis bacteria ascending to kidneys Ureteral stone or obstruction Prostatic secretions contain zinc and are bacteriostatic Urethral length longer in males Host Defenses - Anatomy Vaginal strictures bacterial adhesion time Ectopic ureters Allows bacteria into ureters Bypass urinary sphincter Urine pooling increases bacterial adhesion time Recessed vulva Local moist dermatitis ascending bacteria Host Defense - Mucosal Defense Urothelium prevents water, ions, solutes from passing across urinary tract wall Glycosaminoglycans (GAG) surface layer prevents bacterial adhesion Mechanical disruption stones Chemical disruption cytoxan 14 Host Defense Antimicrobial properties Urine is inhibitory to bacterial growth Concentrated urine Acidic of urine 2

3 Dilute and basic urine supports bacteria growth as well as a nutrient broth Host Defense - Systemic disease 101 dogs with DM, HAC or both 42% had UTI Dogs on long term steroids or Atopica have 18-39% incidence of UTI Incidence in cats 17-30% with CKD 12% with DM 20% with Hyperthyroidism Normal host defense can clear infection with minimal to no antibiotic therapy Host defense abnormality more prone to infection with less virulent organisms More severe infections More extensive therapy More precise therapy Classification of UTI Location Complexity Response to therapy/persistence Simple vs. Complicated Simple = No underling structural or functional abnormality suspected or found Complicated = Compromised host defenses Involve kidneys or prostate Types of Recurrent UTIs Relapse Re-infection Superinfection Relapse Same bacteria as initial infection Reoccurs within several days after d/c antibiotics Usually indicates antibiotic problem Resistant infection Antibiotic can t penetrate into thickened bladder wall, stone, tumor, etc. Poor owner compliance Dose or duration was incorrect Re-infection Initial infection was cleared (neg culture) Culture now shows different bacteria Time between infections usually longer Indicates compromised host defenses Antibiotics can sterilize the urinary system while they are present. Host defenses are 3

4 necessary to prevent recurrent UTIs after stopping antibiotics Re-infection Indicates a problem with host defenses Micturition problem (neurologic?) Anatomic issue? Disruption of mucosal defense (stones? Polyps?) Underlying systemic disease? Super-infection A new bacteria colonizes the urinary system while patient is currently on antibiotics Urinary catheter is most common reason Surgical intervention cystotomy, urethrostomy Severe immunocompromise Treatment of Urinary Tract Infections Simple, uncomplicated UTI Choose first line antibiotic Base on Gram stain of urine sediment Empirical amoxicillin, cephalexin, TMS? Treat for 7-10 days Signs should resolve within 48 hours Complicated UTI Consider location Kidney Enrofloxacin, TMS? Prostate TMS, enrofloxacin, chloramphenicol Base on culture and sensitivity results Drugs excreted in urine will reach high concentration Prolonged course of treatment 4-6 weeks is usual length of treatment Drugs excreted in urine Relapsing UTI Choose appropriate antibiotic based on C&S Re-evaluate dose and duration of treatment Review compliance issues Look for reasons for poor penetration Consider therapeutic urine cultures Therapeutic Urine Cultures 1. Base initial antibiotic choice on diagnostic C&S 2. Culture 5-7 days after starting Did the antibiotic clear the infection? 3. Culture one week before finishing antibiotics Did a superinfection grow during treatment? 4. Culture again 7-10 days after finishing 4

5 Is there another relapse or re-infection? Re-infection A different bacterial infection after stopping antibiotics Workup for causes of impaired host defenses (anatomy, systemic disease, immunocompromise, neurologic bladder) Treat and/or fix the underlying problem Consider therapeutic urine culture Is it the same bacteria? Antibiotic sensitivity profile? Distinguishes between relapse vs. reinfection only 58% of the time Pulsed-field gel electrophoresis (PFGE) Genetic fingerprinting Relapse vs. re-infections How do I interpret my sensitivity profile? Minimum Inhibitory Concentration MIC is the lowest concentration that inhibits growth of the pathogen. (90%) Mean urine concentration of antibiotic should exceed MIC by at least 4 times for antibiotic to be effective especially if patient is immunocompromised Breakpoint MIC Highest drug concentration that can safely be achieved. It is specific to the species and drug. It will be the same for any bacteria For example, the breakpoint MIC for amoxicillin in the dog is =>32 Urine concentration vs. plasma Susceptibility is done based on plasma concentrations of drugs Many antibiotics reach higher concentrations in the urine than can safely be reached in plasma. For resistant organisms choose antibiotics that are concentrated in the urine S vs I vs R Any wiggle room? Susceptible > 80% chance of success MIC is within breakpoint Intermediate Might still work if you can increase the urine concentration MIC is at high end of breakpoint Resistant - Never gonna happen. MIC is at or above breakpoint An example Urine culture grew E. coli 5

6 Which antibiotic should we pick? Increasing concentration Time dependent antibiotics Penicillins, cephalosporins Maintaining constant levels is important Usually dosed every 6-12 hours Increase FREQUENCY to increase concentrations Concentration dependent antibiotics Fluoroquinolones, aminoglycosides Reaching maximum concentration is important Drug has a post-antibiotic effect Should usually be dosed q 24 hours Increase DOSE to increase concentrations Urinary catheters Risk of a UTI increases with catheter Increases 27% each day catheter is in place Increases by 450% if already on antibiotics Intermittent catheterization is less risk than indwelling catheter Avoid antibiotics if possible Sometimes you just can t win The underlying host defense problem can t be fixed Consider a preventative protocol Low-dose, preventative protocol 1. Clear infection and have negative culture 2. Use first-tier antibiotic that is excreted in the urine (amoxi, cephalexin) 3. Calculate 1/3 TOTAL daily dose 4. Give at night after last urination Risk is antibiotic resistance Try to consider this a last resort option of treatment But the darn dog developed an UTI while on this protocol. Treat as a complicated urinary tract infection Treat for 4 weeks based on culture and sensitivity results Culture at the end to make sure that infection is cleared Immediately go back on low dose preventative protocol Methenamine 6

7 Urinary antiseptic In acidic urine (ph < 6) is metabolized to formaldehyde which creates an inhospitable environment Contraindicated in renal disease (metabolic acidosis), liver disease (ammonia load), and TMS (inactivates, kidney damage) Preventative can t treat a current infection Cranberry Proanthocyanidins (PAC) - Inhibits adhesion of E. coli fimbriae Preventative, not a treatment (1mg PACs/kg) 16mg/tablet Crananidin - By day 7, anti-adhesion activity in the urine at 78% The culture keeps growing but the patient has no signs of UTI! Subclinical bacturia Treatment may not be necessary if there are no clinical signs or urine sediment evidence of UTI Exception is patients with high risk of ascending infections (immunocompromised, renal disease) Consider an antibiotic break Antibiotic Break Multi-drug resistant organisms may be replaced with susceptible bacteria if treatment is withheld. Withhold treatment and re-culture in 2-3 weeks. Risk of ascending infection, septicemia Consider risk factors (renal disease, immunocompromise) I keep culturing this horrible, multi-drug resistant Enteroccocus sp! Enterococcus UTI Not virulent, usually opportunistic, inherently resistant to many antibiotics Hospitalized patients nosicomial Immunocompromised patients Inherently resistant to TMS in vivo Treat underlying host defense problems Risk of non-treatment? Penicillins are antibiotic of choice Two organisms were cultured and they are both resistant! Culturing two different organisms Ideally choose an antibiotic that treats both Consider combination therapy prioritize the more virulent organism Bacterial counts, pathogenicity Consider relevance of each organism Enterococcus infection will often resolve if the other organism is treated 7

8 55 56 Questions? Presentation notes will be provided tomorrow on our website: Go to 2013 Symposium at Coors Field and click on the title of the lecture. 8