8/28/2019

General Principles
RECURRENT AND
RESISTANT URINARY TRACT • Is there really a clinical UTI?
• Therapeutic Success = Eradication of Infection AND
INFECTIONS IN DOGS Avoidance of Resistance
• Therapeutic Choices
Julie K. Byron DVM, MS, DACVIM • Bacteria
The Ohio State University • Patient
Veterinary Medical Center • Drug
• Safety
• Antibiotics are not innocuous drugs

Mechanisms of Resistance Mechanisms of Resistance

• Inherent Resistance – organism is resistant because it
lacks the antibiotic target
• Acquired Resistance – a previously susceptible
organism becomes resistant
• Random DNA mutation
• Ex: anaerobic organisms are resistant to aminoglycosides
because its uptake into the cell is oxygen dependent • Plasmid/transposon transfer of DNA by transduction or
conjugation

The Development of
MIC and MPC
Resistance
• MIC (minimum inhibitory concentration) – tube with the
• Documented increases lowest concentration of drug that has no growth
in antibiotic resistance • Breakpoint MIC – standard lowest concentration of a drug that will
among canine UTI inhibit growth. MICs close to this are considered resistant
isolates (Seguin, 2003)
• 1989: 95.2% • MPC (mutant prevention concentration) – concentration
• 1998: 59.2% of drug needed to prevent mutant emergence (no growth
escape)
• Susceptibility to at
least 1 commonly
prescribed PO
antibiotic

1
 8/28/2019

How do we choose? Which abx are best for this organism?

• Does this animal need antibiotics? • Empirical Therapy

• We will touch on this later • Common
• Justifiable
• What antibiotic should I use? • Limited Utility
• Know when to culture
• What dosing regimen is best?

Dosing Regimen? Dosing Regimen?

MPC

Dosing Regimen? Dosing Regimen?

• Time Dependent – T > MIC most important • Concentration Dependent – Cmax/MIC most important
• Usu. Multiple times a day dosing • Often once a day dosing

Fluroquinolones
Β-lactams (penicillins)
Aminoglycosides
Cephalosporins
Macrolides (erythromycins)
static

2
 8/28/2019

Lower Urinary Tract – Urinary Tract Infections

Normal Defenses
Dogs Cats
• Micturition - flushing
• Anatomic Barriers • Females > Males • > 10 years old
• High pressure zones • ~14% of dogs during life • < 1 - 7% in young cats
• Urethral and ureteral peristalsis • All ages, possibly more
• Prostatic secretions common in older females
• Mucosal Defenses
• Urothelium
• GAG layer
• Antibody production
• Urothelial exfoliation

Urinary Tract Infections Sporadic Bacterial Cystitis

• Sporadic cystitis (uncomplicated) • ≤ 1-2 UTIs/year

• Recurrent bacterial cystitis (complicated) • No immunosuppression

• Relapsing • No underlying abnormalities to predispose to UTI

• Reinfection • No history of abx use in last 1-2 months

Sporadic Bacterial Cystitis Recurrent Bacterial Cystitis

• Consider NSAIDs for comfort
• Amoxicillin or SMZ-TMP empiric therapy • 3+ in 12 months or 2+ in 6 months
OR • Immunosuppression
• Culture and treat based on results • Predisposing illness
• Bladder/urethral mucosal damage
• Treat for 3-5 days • Urine retention
• If no response in 48 h, culture and investigate further • Urinary incontinence
• Alterations in urine volume or concentration
• Fluoroquinolones are NOT recommended • Anatomic defects of urogenital tract

3
 8/28/2019

Recurrent Bacterial Cystitis Relapsing UTI

• Repeated UTI which occurs after therapy has been • Recurrence by the same organism within 6 months
discontinued • Within days of stopping antibiotic
• Not fully eliminated by previous treatment
• Wrong treatment
• Relapsing • Nidus of infection
• Anatomic defects
These can be difficult to distinguish
• Functional defects
• Reinfection • Tissue penetration

• Often more difficult to treat than reinfections (may need

longer treatment, 2w)

Reinfection UTI Recurrent UTIs

• Causes of relapse
• UTI with a different organism than the one previously • Deep nidus of infection
(may be same genus or species though) • Poor penetration to the site (kidney, prostate)
• Dissolving uroliths
• Defect in host defenses
• Causes of reinfection
• Poor immune function
• Weeks or months after previous infection • Systemic disease
• Anatomic abnormality (ectopic, “hooded vulva”)
• Usually eliminated with appropriate therapy (3-5d), but • Urine retention
need to investigate reason for reinfection • ETC.

Recurrent/Resistant
Treatment Failure
UTIs
• Wrong drug, dose or • Predisposing Factors
duration (resistant?) • Stones
• Systemic disease (Cushing's, DM, etc.)
• Client compliance • Polyps
• Failure of drug to • Neoplasia
reach adequate urine • Foreign Body
concentrations • Prostatitis
• BPH
• Nidus of infection • Anatomic abnormalities
• Anatomical or • Incontinence
functional
abnormalities in LUT

4
 8/28/2019

Recurrent/Resistant UTIs
• Diagnostic Approach
• Culture
• Before
• +/- During (5-7d)
• (Sediment examination before stopping)
• +/- After ABX finished (5-7d)

• Relapse: Find where the infection is hiding

• Reinfection: Look for an underlying predisposing cause or

breakdown in local defenses

Recurrent/Resistant UTIs Therapeutic Plan

• Therapeutic Considerations and Treatment Options • Be sure clinical infection is present

• If it is a complicated/recurrent infection, culture before
treating and get a sensitivity panel
• Choose ABX that penetrate the tissues of interest (prostate,
kidneys/sulfas, quinolones)
• Treat underlying problems (stones, polyps, etc)
• Optimal duration of therapy (?)
– Little research
– 3-5d, 7-14d
• Urine culture/sensitivity via cystocentesis
• Appropriate abx at adequate dose
• 3-5 days if reinfection
• 1-2 weeks if recurrence
• Re-culture 5-7 d after start of abx
• If not sterile, reconsider drug/dose/compliance
• Re-culture 5-7 d after completion of abx

Therapeutic Plan Truly Resistant UTIs

• Suppressive/preventive therapy once the urine
is clean (once a day, not without risks though)
• Nitrofurantoin
• Re-culture frequently for breakthrough
• Little evidence of efficacy
• MICs and Breakpoints based on serum concentrations of
antimicrobials
• Urine and renal tissue concentrations of these drugs
may be significantly higher (e.g. penicillins,
fluoroquinolones)

• Follow-up monitoring, q 1 then 3 months

5
 8/28/2019

Urine concentration vs. MIC Prevention Strategies

• Must first address any correctable underlying

abnormalities
• Prophylactic therapy is controversial
• Must demonstrate sterile urine prior to starting
prophylactic therapy to reduce resistance
• No studies comparing pulse therapy to chronic low-dose
therapy

From D Senior, Nephrology and Urology of Small Animals, J Bartges, D Polzin eds., 2011

What About
Prophylactic Therapy Cranberry Extract?
• Low dose abx not designed to treat a current infection – • Proanthocyanidins
Urine clean at start – Block E. coli P-fimbriae from adhering to uroepithelium
• Medication at bedtime to increase bladder exposure time – Appears to work in vitro, not so much in vivo
• ½ - ⅓ daily dose
• Gram-neg: Nitrofurantoin, TMS, Cephalexin
• Gram-pos: TMS, Amoxi/Clav
• Culture urine q 4-8 weeks to verify continued sterility
• May stop after 6 months of sterile urine

D-Mannose? Probiotics?
• R, D-Mannosides block FimH mediated bacteria=host
cell interaction that initiates invasion • Humans: vaginal flora changes with UTIs
• Re-establishment of normal flora may help prevent recurrence

• Reduces adherence of bacteria to mare uterine cells in

vitro • Dogs: no difference in vaginal flora with and without UTI
• Urethral and vaginal microbiome very similar unlike in humans

• RCT in humans showed better than no treatment

• Live biotherapeutics (E. Coli strains) – some evidence
• Safe, but no universal dose regimen
• Can be useful for ‘Puppy Vaginitis’
• No evidence of efficacy in vet med

6
 8/28/2019

ISCAID Recommendations
2019
Is There a UTI?

• Prophylactic antimicrobial therapy not recommended

• Pollakiuria and • Physical examination
hematuria can have • CBC?
• Treat with the aim of clinical cure, not microbiological
many causes • Imaging (rads, US)
cure
• Uroliths
• Culture
• Neoplasia
• Insufficient evidence to recommend cranberry or • Cystoscopy
methenamine • Idiopathic cystitis (cats)

“Occult” UTI = Asymptomatic Bacteriuria Devil’s Advocate…

• Do we have to treat asymptomatic infections?
• No clinical signs of UTI • Bacteriuria vs. UTI
• Colonization vs. infection
• Clears on its own?
• Incidental finding on UA/culture • Role of ‘non-pathogenic’ bacteria?
• 8.9% (12% young to middle age, 6% older) female dogs have
subclinical bacteriuria (Wan, 2014)
• +/- Pyuria
• Enterococcus species?
• Bacteriuria seen on sediment • Opportunistic?
• 70-75% of infections are single organism (Ball, 2008; KuKanich, 2015)
• Often MDR
• Target other bacteria in mixed infection

‘Positive’ Urinalysis? Humans

• Poor correlation between UA and culture results
• 13.6% (19/140) healthy dogs had WBCs or bacteria on UA
• Only 2.1% (3/140) had bacterial growth on urine culture
• McGhie, Aust Vet J, 2014
• Gram or Wright staining of air-dried urine sediment may
improve sensitivity and (most important) specificity
• Way et al, JVECC, 2013
• Asymptomatic bacteriuria is not harmful
• Women with + culture who were treated had more complications
than those not treated
• Only recommend treating pregnant women and those
undergoing prostate or other invasive urogenital surgery
if asymptomatic
• i.e.: diabetics and immunosuppressed individuals NOT treated if
asymptomatic

• Eliminate predisposing factors like indwelling u-catheters

• Prefer to do repeated catheterizations
• Avoid antimicrobial use when a catheter is present

7
 8/28/2019

Questions?