Management of UTI

UTI
• A very common out-patient problem, especially in
women
• 1/3 have one UTI by age of 24
• >1/2 will have at least one UTI in life-time
• A large number of urology SOPD referrals are for
“recurrent UTI” / “persistent dysuria”
• Overalap in symptomatology with patients with CPPS,
OAB, IC, BPH/LUTS
 Clinical types of UTI
• Acute
• Cystitis
• Pyelonephritis
• Pyonephrosis / renal abscess
• Prostatitis
• Epididymo-orchitis
• Urethritis / STD
• Others
• Mycobacterial, parasitic, fungal
 UTI
• Uncomplicated
• In anatomically, physiologically normal urinary tract with
normal host defense mechanisms (i.e. otherwise normal
individuals)
• Complicated
• Eg. neuropathic bladder, urinary tract obstruction, bladder
diverticulum, presence of stones
• ↑Risk of acquiring infection and failing treatment
• Special groups
• Pregnancy, children
UTI
Uncomplicated UTI Complicated UTI

• “Usual” uropathogens • Broader spectrum of bacteria

(E.coli 70-95%) (often Rx-resistant)
• Shorter duration of • Longer duration of treatment
treatment
• May require admission
• Out-patient treatment
• True cure without recurrence
• Complete cure very likely not possible unless
complicating features
eradicated
Workup of suspected UTI
• History
• Associated gross hematuria?
• Previous antibiotic treatment
• Presence of “complicated” features
• Eg. neuropathic bladder, renal stone,
previous surgery to urinary tract
• Recurrent attack?
• Social & drug history : ?ketamine use
Workup of UTI
• Urinalysis
• Urine culture

• (Creatinine)
• (Imaging)
 Role of imaging in UTI
• EAU Guidelines on UTI
• Uncomplicated cystitis in women
• No role of imaging

• Uncomplicated pyelonephritis in women

• Ultrasound : to rule out underlying stones / obstruction
• Further imaging eg CT kidneys : if symptoms / signs not improving 72
hrs after starting treatment

• Johnson et al Clin Infect Dis 1992;14:15

• Not necessary due to low diagnostic yield
 Role of imaging in UTI
• UTI in men
• Very small number of UTI in men aged 15-50 are
uncomplicated
• Most men with febrile UTI have concomitant infection of
the prostate (prostatitis)
• Urologic evaluation including imaging indicated in
• Men with febrile UTI
• Men with pyelonephritis
• Men with recurrent infection
• UTI with complicating factors suspected
 Urinalysis
• Gross examination
• Biochemical examination
• pH
• Specific gravity
• Urinary dipstick
• Osmolality
• Leukocyte esterase
• Nitrites
• Microscopic examination
• Pyuria (WBC)
• RBC
• Cell casts
• Dysmorphic cells
• Leukocyte esterase
• Enzyme produced by neutrophils
• Hence LE+ve suggests pyuria
• False positive
• Contamination by vaginal discharge
• Presence of formalin
• False negative
• High specific gravity
• Dehydration
• Glycosuria
• Presence of urobilinogen
• Large amount of Vitamin C ingestion
• Test read too late (WBC lysis)
• Sensitivity for UTI detection : 70-95%
• Nitrites
• Not normally found in urine
• Most Gram-negative bacteria can convert nitrates in urine
to nitrites
• Hence nitrites +ve suggest bacteriuria
• False positive
• Contamination by vaginal flora
• False negative
• UTI due to non-fermenters (eg. Pseudomonas) and Gram positive
organisms
• Too dilute urine (low specific gravity)
• Sensitivity of UTI detection : 35-85%
• Specificity of UTI detection : 92-100%
• Urinary pH
• Normal urinary pH 5.5 – 6.5
• An overly alkaline urine (>7.5) suggest infection by an
urease-producing organism, esp. in the presence of
stones
• Eg. Proteus, Klebsiella, Pseudomonas etc
• Urea converted by bacteria to ammonia,
• raises pH
• facilitates precipitation of struvite calculi (magnesium
ammonium phosphate or "triple phosphate stone)
Urine microscopy
• Important part of urinalysis
• Detects pyuria, microhematuria, dysmorphic cells
and cell casts
• Pyuria
• Defined as >/= 10 WBC/mm3
• Important adjunct to differentiate contamination from
true bacteriuria
 Sterile pyuria
• Pyuria without bacteriuria
• DDx :
1. Tuberculosis
2. Bladder cancer (carcinoma-in-situ)
3. Urinary tract stones
4. Schistomsomiasis
5. Partially treated UTI
6. Other inflammatory bladder conditions eg. interstitial
cystitis, ketamine cystitis
Urine culture
• Mid-stream urine (MSU)
• Commonest method of urine collection for culture
• Prone to contamination
• Up to 1/3 specimens contaminated in female patients
Bent et al Am J Med 2002; 113: 21-8
MSU instructions
• Female
• Spread the labia, cleanse the periurethral area with a
moist gauze from back to front
• Clean-catch the 10-15ml of urine, after the initial 100-
150ml has been voided

• Male (uncircumcised)
• Retract foreskin, wash glans with soap and water
• Keeping foreskin retracted, collect 10-15ml urine as
above
 Urine culture
• Traditionally
>/= 105 CFU taken as the definition (Kass 1960)
• Generally lower cut-off used for symptomatic patients
• Uncomplicated cystitis : >/= 103 CFU
IDSA / ESCMID Guidelines
• Uncomplicated cystitis : >/= 102 CFU
Stamm et al NEJM 1982; 307: 463
• Uncomplicated pyelonephritis : >/= 104 CFU
IDSA / ESCMID Guidelines

Infectious Diseases Society of America (ISDA)

European Society for Microbiology and Infectious Diseases (ESCMID)
IDSA / ESCMID
Treatment
• Uncomplicated cystitis
• Antibiotics for 3 days (except nitrofurantoin, which
should be given for 7 days)

• Uncomplicated pyelonephritis
• Antibiotics for 10-14 days
• Admission may be required for severe cases
FAQ

1. Asymptomatic bacteriuria - should we treat?

2. Approach to patients with recurrent UTI?
Asymptomatic bacteriuria
• Needs to be differentiated from contaminated
specimen
• Useful clues to ?contamination
• Dipstick / urinalysis results
• Leukocyte esterase
• Nitrites
• Microscopy results
• Pyuria
• Squamous epithelial cells
Genuine UTI / bacteriuria
• Dipstick
• Leukocyte esterase : positive
• Nitrites : positive
• Microscopy
• Pyuria (>10 / mm3)
• +/- microscopic hematuria
• Urine culture positive and pure growth
• Absence of squamous epithelial cells
Contamination
• Dipstick
• Leukocyte esterase : negative
• Nitrites : negative
• Microscopy
• Absence of pyuria
• No microhematuria
• Urine culture positive / polymicrobial growth
• Presence of squamous cells
Asymptomatic bacteriuria
• Defined as >/= 105 CFU and >/= 103 CFU in women
and men respectively (MSU)
• Occurs in 4-7% of women
• Presence of pyuria in the absence of symptoms /
signs does not equate presence of clinical UTI
EAU Guidelines on UTI
 Asymptomatic bacteriuria
• Screening and treatment of asymptomatic bacteriuria is
not indicated in
• Premenopausal non-pregnant women
• Postmenopausal women
• Men
• Patients on indwelling catheters
• Patients on nephrostomy tubes / ureteric stents
• Patients with spinal cord injury
Asymptomatic bacteriuria
Screening and treatment of asymptomatic
bacteriuria is recommended only in
1. Pregnant patients
2. Patients about to undergo invasive genitourinary
procedure for which there is risk of mucosal bleeding
 Bacteriuria in special groups
• Pregnancy
• Incidence of asymptomatic bacteriuria is similar to non-
pregnant patients (4-7%)
• Physiological changes (marked rise in GFR, hydronephrosis
and hydroureter) makes progression from bacteriuria to
upper tract infection likely (up to 25-40%)
• Upper tract infection during pregnancy associated with
prematurity, LBW etc
• Hence routine screening and treatment of bacteriuria is the
standard of care
Asymptomatic bacteriuria in DM
• Asymptomatic bacteriuria in diabetic women
• Very common (26%)
Geerlings et al Diabetes Care 2000 Jun;23(6) : 744-9
• DM patients are prone to rapid progression of renal
parenchyma infection if occurs
• Screening and treating bacteriuria makes sense
 Should asymptomatic bacteriuria in
DM patients be treated?
• Double-blinded placebo-controlled study
• Treatment of asymptomatic bacteriuria does not
reduce complications in diabetic patients
• Concluded that screening and treatment of
asymptomatic bacteriuria in DM patients not clinically
indicated

Harding GK et al Manitoba Diabetes Urinary Tract Infection Study Group. Antimicrobial treatment of diabetic
women with asymptomatic bacteriuria. N Eng J Med 2002 Nov;347(20):1576-83
Recurrent UTI
• Estimated 25% to 50% of women will suffer from
recurrences after UTI
• Recurrent UTI
• Defined as symptomatic UTI that follows the
documented resolution of a previous one, occurring at a
frequency of at least 2 times within last 6 months, or 3
or more times in the last 12 months
Recurrent UTI
• Bacterial persistence / relapse
• Recurrent UTI caused by the same organism, frequently
from a focus within the urinary tract (eg. stones, urethral
diverticulum)
• Bacterial reinfection
• Recurrent UTI caused by different organisms or same
organism but separated by documented periods of no
growth in urine
• Source of organisms likely reservoir in fecal flora
• Indicates underlying susceptibility (eg. genetic) to UTI
• >95% of recurrent UTI are due to reinfection
Risk factors for recurrent UTI
• Premenopausal women
• Sexual intercourse
• Frequency
• New partner
• Use of spermicide and diaphragm
• Pelvic anatomy (urethra-to-anus distance)
• Age of first UTI
• Family history (genetic factors)
• Prior antimicrobial use
Scholes et al J Infect Dis 2000;182:1177-82
Risk factors for recurrent UTI
• Postmenopausal women
• Estrogen deficiency
• Urinary incontinence
• Presence of cystocele
• Large post-void residual urine
• Hx of UTI before menopause
• Genetic factors
Raz et al Clin Infect Dis 2000;30:152-6
 Evaluation of recurrent UTI
• History
• Pre/postmenopausal state
• Sexual history, spermicide / diaphragm use
• ?upper tract involvement (loin pain, fever)
• Detailed account of UTI episodes
• Frequency
• Relationship with coitus
• Other triggering factors
• Previous culture and antibiotic treatment
• Possible factors leading to relapse (eg. previous urologic
surgery, urinary tract stones)
Evaluation of recurrent UTI
• Examination
• ?Ballottable kidney (hydronephrosis)
• ?Palpable bladder suggestive of voiding dysfunction
• Assess degree of estrogenisation of introitus and vagina
• ?Cystocele / uterine prolapse
• ?Periurethral fullness / mass (urethral diverticulum)
• Focused neurologic examination (DRE)
Workup of recurrent UTI
• Urinalysis and culture
• To confirm presence of recurrent UTI
• To determine bacterial persistence from reinfection
• Imaging studies
• Not routinely recommended in evaluation of women
with recurrent UTI
EAU 2017 Guidelines on UTI
• Rare to find significant abnormalities
Hooton et al Int J Antimicro Agents 17(2001) 259-68
 Workup of recurrent UTI
• Further workup probably indicated in patients with
recurrent UTI AND :
• Gross hematuria
• Persistent microhematuria in between UTI
• Evidence of bacterial persistence
• Suspicion of complicated UTI
• Urea-splitting organism (urease +ve)
• Symptoms / signs of urinary tract obstruction (eg. ballottable mass,
palpable bladder)
Dielubanza et al Med Clin N Am 95 (2011) 27-41
Nickel et al Can J Surg. 1991 Dec; 34(6): 591-4
Management of recurrent UTI
• General measures
• Avoid the use of spermicides / diaphragms
• Observe personal hygiene*
• Post-coital voiding*
• Hydration to maintain adequate urine output*

*Never shown in case-controlled studies to be associated

with reduced risk of recurrent UTI
Management of recurrent UTI
• Specific measures
• Topical vaginal estrogen
• Antibiotic prophylaxis
Topical estrogen
• Rationale
• Estrogen stimulates proliferation of lactobacilli in vaginal
epithelium ► reduces vaginal pH ► decreased
colonization of vagina by Enterobacteriaceae
• Intravaginal estriol cream significantly reduces
vaginal colonization by coliforms and decreased the
incidence of UTI
• 0.5 mg of estriol in vaginal cream once each night
for two weeks followed by twice-weekly
applications for eight months
Raz and Stamm NEJM 1993; 329:753-6
Antibiotic prophylaxis
• Has been demonstrated to be effective in reducing
risk of recurrent UTI
• Indications
• Patients who have documented recurrent UTI and are
bothered enough by it
• Types
• Continuous prophylaxis
• Post-coital prophylaxis
• Self-start therapy (not exactly prophylaxis)
Continuous prophylaxis
• Demonstrated in numerous studies to decrease
recurrences by 95%
• Most authorities advocate 6-month course of
nightly low-dose
• Breakthrough infections (~5%) should be treated
with full course of full-dosed antibiotics
Example : Septrin 480mg, nitrofurantoin 50mg,
trimethoprim 100mg, cephalexin 250mg
Post-coital prophylaxis
• Single-dose antibiotics after coitus
• Effective for those who have recurrent UTI
temporally related to sexual intercourse
• Results in less consumption of antibiotics than
continuous prophylaxis

Example : Septrin 480mg, Ciproxin 125mg

 Self-start Therapy
• Not exactly prophylaxis
• Restricted to motivated, self-conscious patients
• Patients start 3-day course of antibiotics once symptoms of
UTI noticed, with or without saving a MSU first
• Studies showed 86% of symptomatic episodes were culture
positive and 92% achieved symptomatic relief
Schaeffer et al J Urol 1999; 161:207-11
EAU Guidelines on UTI
 Red flags
1. “Recurrent” UTI with gross hematuria or persistent
microscopic hematuria
• Formal urologist referral required to rule out malignancy
(requires cystoscopic assessment)
2. Recurrent bacterial persistence, especially with
urease-producing organisms
• May indicate underlying urolithiasis
3. Recurrent UTI with pyuria but no growth
• Needs early morning urine (EMU) for TB
• Needs to rule out stone formation
• Is this ketamine cystitis?
 What is normal host defence
mechanisms against UTI?
• Normal commersal flora of vaginal
• Lactobacilli reduced uropathogens to colonise by lowering
pH as a result of converting glycogen to lactic acid
• Normal antegrade flow of urine
• Vaginal oestrogen and IgA
• Normal exfoliation of urothelial cells
• Tamm-horsfall protein by ascending limb of loop of
Henle – bind type 1 pili
• GAG layer
• Osmolality, pH of urine
How to prevent recurrent UTI?
• Apply oestrogen to atrophic vagina to restore normal vaginal
environment and re-colonization with lactobacilli and reduce
recurrent UTI (Raz)
• Avoid the use of spermicides / diaphragms
• Antibiotics (Post-Coital / Self-start / Prophylaxis)

• Observe personal hygiene*

• Post-coital voiding*
• Hydration to maintain adequate urine output*
• *Never shown in case-controlled studies to be associated with
reduced risk of recurrent UTI i.e. not evidence-based
 How to prevent recurrent UTI?
• Continuous antibiotics (6-12 months, 95% reduction of recurrence, but
60% reinfected after stopping the antibiotics)
• Ciprofloxacin 125 mg, Septrin 480mg, trimethoprim 100mg,
cephalexin 250mg
• Nitrofurantoin 50 mg once daily – lower systemic absorption and
less microbial resistance, but avoided in pyelonephritis as tissue
level in kidney is low
• Avoid amoxicillin and cephalosporin which change fecal flora
• Postcoital antimicrobial prophylaxis
• Recurrent uncomplicated cystitis, self-diagnosis and self-treatment
with 3-day course regimen of an antimicrobial with MSU beforehand.
If failed > send MSU for proper culture
• Cranberry juice (Proanthocyanidin: 36 mg/Day) – block bacterial
adherence to urothelium, 20% ↓ Risk of infection
Q&A
Case
• F/40
• Good PH
• HPI:
• Acute left loin pain
• Low grade fever
• Vomiting (secondary to paralytic ileus)
• PE:
• BP 120/60, p 110, temp 37.8
• Abd soft, left loin mild tenderness, no mass,
• KUB: no stone
• Urine stix: nitrate+, WBC+, RBC +
• Bedside USG: no hydronephrosis/stone
• CBC: WCC 14, Hb 12
• RFT Cr 100, CaPO4, urate normal
Case
• Imp: Acute pyelonephritis
• IV zinacef
• Progress
• Low grade fever and tachycardia
• Left loin pain slightly improved
• Not septic looking
• DDx?
• Ix?
KUB
CT
• Mx?
EPN (Emphysematous pyelonephritis)
causes and pathogenesis
• EPN is an acute severe necrotizing infection of the
renal parenchyma and its surrounding tissues that
results in the presence of gas in the renal
parenchyma, collecting system or perinephric
tissue
EPN pathogens
• Most common: E-coli and klebsiella
• Others:
• Proteus, Steptococcus and pseudomonas
EPN pathogenesis
• Factors
• High glucose level
• Gas-forming microbes
• Impaired vascular blood supply
• Reduced host immunity
• Urinary tract obstruction
• Mechanism
• G-ve facultative anaerobes e.g. E coli produce gas via fermentation
of glucose  high levels of nitrogen, oxygen, CO2 and H2
accumulating at inflammatory site  gas may extended the
inflammatory site to subcapsular, perinephric and pararenal spaces
EPN histopathology
• Abscess formation
• Foci of micro and macro-infarction
• Vascular thrombosis
• Numerous gas-filled spaces
• Area of necrosis surrounded by
acute and chronic inflammatory
cells implying septic infarction
EPN associated factors
• DM
• Single most common factors
• Female > Male
• Urinary tract obstruction
• Stone
• immunocompromised
EPN diagnosis
• Radiological Dx
• Gold standard: CT
• CT: more sensitive and define
extent of EPN by identifying
features of parenchymal
destruction

• KUB: abnormal gas shadow in

renal bed
EPN classification

• Wan: used in 2 meta-analysis, prognostic value, type 1 >

60% mortality, type2 > 20% mortality
• Huang and Tseng: for Mx
 EPN management
• High index of suspicion in pt fail medical treatment for acute
pyelonephritis
• Active resuscitation - ABC
• Medical Mx (MM)
• O2, IVF, Acid base balance, Abx, good glycaemic control
• Keep SBP >100 with IVF +/- inotropes
• Empirical Abx: AG, b-lactamase inhibitor, CS, quinolones,
till c/st a/v
• Renal support if ARF
• ICU care if multiorgan support need
• Huang and Tseng classification
• Class 1 (gas in collecting system only): PCD + MM
• Class 2 (parenchymal gas only): PCD +MM
• Class 3 (3A peripheric gas, 3B pararenal gas):
• Depend on risk factors:
• Diabetes, thrombocytopenia, acute renal
failure, altered level of consciousness,
shock
• 0-1 risk factor: PCD+MM survival rate 85%
• >=2 risk factors: failure 90%  nephrectomy
• Class 4 (soliatory kidney/Bil EPN):
• PCD + MM
• If failed to respond: Nephrectomy + ICU + renal
support
Q21

Patient in ICU from septic shock

 Diagnosis? (1)
 Any classification that you are aware of? (1)
 Name one predisposing factor (1)
• Left emphysematous pyelonephritis

• One classification proposed by Wan et al

• Type I : parenchymal destruction with either an absence
of fluid collection or presence of streaky or mottled gas
(mortality 60%)
• Type II : renal or perinephric fluid collection with bubbly
or located gas or gas in the collecting system (mortality
20%)

• Diabetes mellitus (esp uncontrolled)

Loin pain and fever. CT scan. Diagnosis?
Loin pain and fever
• Stone with psoas abscess
Patient with dysuria,
KUB
Patient with dysuria
• What is seen on KUB?
• What is the cause?
Emphysematous cystitis
• Necklace appearance of gas beads in bladder wall
diagnostic of emphysematous cystitis
• due to infection by gas forming organisms
(commonest E Coli) in an immunocompromised
patient (usually DM)
Emphysematous Cystitis
EC
• DDx:
• Intrumentation • Pathogens:
• Fistula to hollow viscus • Similar to EPN
• Tissue infarct with necrosis
• Infection
• Pathogenesis:
• EC more common in • like EPN,
• Middle aged diabetic women (M: F • non-diabietic: urinary
= 1:6) albumin as substrate
• Predisposing factors
• DM (66%), Chronic UTI, indwelling
urethral catheter, urinary stasis
due to BOO, neurogenic bladder
• Various s/s
• Asymptomatic, pneumaturia,
irritative voiding, acute abdomen
to severe sepsis
EC
• Radiological Dx • Histopathology
• KUB: curvilinear area of • Gross:
radiolucency delineating the • Bladder wall thickening
bladder wall with or without with vesicles of varying
intraluminal air size
• CT: more sensitive, define • Microscopic:
extent and severity, • multiple gas-filled vesicles
predominantly within the
differentiate vesicoenteric bladder mucosa, lined by
fistula, intraabdominal flattened fibrocytes and
abscess, adjacent neoplastic multinucleated giant cells
disease, EPN
EC management
• MM:
• Abx, bladder drainage, DM control, correct underlying
comorbidities
• If fail to respond/severe necrotizing infection (10%)
• Consider partial cystectomy, cystectomy or surgical
debridement
• EC alone Mortality 7%
• EC + EPN Mortality 14%
Xanthogranulomatous
pyelonephritis
Q68
• KUB and CT scan of a patient with vague R flank
pain and ballottable mass
• What is the diagnosis? (3)
• Under microscopy, what is a characteristic feature
in this condition? (2)
• KUB : multiple renal stones in R kidney
• CT : classic “bear’s paw” appearance, lower cut
showing stones inside dilated calyces
• Dx : Right xanthogranulomatous pyelonephritis
• Lipid-laden macrophages (Xanthoma cells)
Biofilm
Biofilm

• The accumulation of microorganisms and their

extracellular products to form a structured community on
a surface
• Components
• Linking film layer (bottom) which attaches to the surface of the
object
• Base film layer of compact microorganisms
• Surface layer on the outer side from which planktonic bacteria
can arise and spread
• Steps in formation
• mucopolysaccharides layer of bacteria adsorb onto device
surface to form a conditioning film
• Microorganisms attach onto surface
• Further “cementing” of these organisms onto surface by
upregulating surface adhesions / adhesive factors
• Organisms cluster together to form colonies and a basic
biofilm community is formed (10-20% bacteria, 80-90%
muco-polysaccharide matrix)
• Reasons why biofilms cannot be eradicated with
medical treatment alone
• Glyocalyx / mucopolysaccharide layer restricts
access and diffusion of antimicrobial and hence in
effect bacteria continues to survive. This is termed
extrinsic resistance
• Growth rate of bacteria inside biofilm varies and
may be very slow growing and not susceptible to
antimicrobials
• Bacteria within biofilm are phenotypically different
from ordinary bacteria, possibly from a genetic
change. This is termed intrinsic resistance
• Bacteria and adapt to external environment outside
of biofilm and exchange resistance genes (plasmids)
within the biofilm
• As a result, bacteria can survive the concentration of
antimicrobial 1000x higher than those that kill the
planktonic bacteria. The fact that we are culturing
the planktonic bacteria does not help to eradicate the
bacteria inside the biofilm
• Why it is important :
• Biofilms are responsible for many prosthesis-related
infection in urology as well as many “chronic” infections
in urology
• Examples : Infection of AUS / penile prosthesis, ureteral
stent-related infections, chronic prostatitis, infectious
stones
• Treatment
• Antimicrobial useful in young biofilm (<24hrs)
• For older biofilms, device needs to be removed
• Biofilm formation can be avoided / altered by
• Device
• Device with controlled release of antibiotics
• Device with antiadhesive surface
• Surface coating of heavy metals such as silver
• Use of antimicrobial agents prophylactically during
its insertion
• Attention to details during operation of insertion
• Meticulous tissue handling (minimize tissue
devitalisation) and aseptic handling of prosthesis
• Foci of infection elsewhere in the body needs to be
eradicated before insertion
• Avoiding traffic in OT
 How does the urinary dipstick –
(blood) work?
• Hemoglobin (Peroxidase) => Chromogen indicator – Orthotolidine (Peroxidase
substrate)
• Positive result = BLUE (but base is Yellow) = GREEN

• False positive:
• Iodine, Hypochlorite (bleach), Menstrual blood, Dehydration, Exercise and
Myoglobin
• False negative:
• Reducing agent, Vitamin C (Reducing agent), Ascorbic acid

• Dipstick positive but microscopy negative – dilute urine

• Microscopic Hematuria: ≥3 RBCs/HPF or >5 RBCs/mL (AUA)
• In ONE properly saved urine sample
• NOT during active UTI episodes (not accurate)
• Leukocyte esterase (+ve if >10 WBCs/mL)
• Enzyme produced by neutrophils => LE +ve suggests pyuria

• Hydrolyses indoxyl carbonic acid ester on dipstick into indoxyl,

which in turn oxidizes diazonium salt chromogen on dipstick,
producing the color change (Orange to Pink)

• False positive
• Contamination by vaginal discharge
• Presence of formalin

• False negative
• High specific gravity
• Dehydration
• Glycosuria
• Presence of urobilinogen
• Large amount of Vitamin C ingestion
• Test read too soon (<2 mins)
• Test read too late (WBC lysis)

• Sensitivity for UTI detection : 70-95%

• Nitrites
• Most Gram-negative bacteria can convert nitrates in urine
to nitrites => Nitrites +ve suggest bacteriuria
• Nitrites react with aromatic amines on dipstick to form
diazonium salt which interacts with hydroxy-
benzoquinolone to form a dye (Griess test - takes 4 hrs)

• False positive
• Contamination by vaginal flora
• False negative
• UTI due to non-nitrate-reductase-producing bacteria
(eg. Pseudomonas) and Gram positive organisms
• Too dilute urine (low specific gravity)
• Absent dietary nitrates
• Urine present in bladder <4hrs

• Sensitivity of UTI detection : 35-85%

• Specificity of UTI detection : 92-100%
 What is the implication of
bacteriuria?
• 10-20% of patients with pyelonephritis have bacteriuria
• Bacteriuria without pyuria may be found
• Bacterial contamination (Presence of Epithelial cells)
• Colonization (asymptomatic bacteriuria)

• When negative for both nitrites and leukocytes 90% of MSU will be
negative for significant bacteriuria

• When positive for both nitrites and leucocytes, 80% will have positive
cultures on MSU
What is the implication of sterile
pyuria?
• Pyuria without bacteriuria (STERILE):
• Stones / Shistosomiasis / FB in bladder
• TB / Chlamydia / CIS bladder
• Empty
• Residual UTI (Incomplete UTI treatment)
• Interstitial Cystitis
• Leukoplakia
• Empty
 What is the gram’s stain?
• Bacterial smear (Gram’s Stain):
• Crystal violet for 1-2 min
• Gram’s iodine for 1-2 min
• Washed / Decolorized by Acetone
• Washed with water
• Counterstained with Safranin for 2 min

• Gram +ve – cell wall that retain the crystal violet dye
• MRSA is a gram +ve coccus. It is present on the skin of about 40% of people.
Over 90% of isolates produce the penicillin binding protein which makes the
strain resistant to penicillin base antibiotics

• Gram -ve – Pink safranin (counter-stain)

Acute and chronic
pyelonephritis
Is it necessary to perform upper
tract imaging?
• If the patients remain febrile after 72 h of
treatment
• Evaluation of the upper urinary tract with ultrasound
should be performed to rule out abscess, urinary
obstruction
• Chronic pyelonephritis – scarred shrunken kidney
What is the antibiotic of choice?
• Augmentin is NOT recommended as a drug of first choice for
empirical oral therapy of acute pyelonephritis. It is
recommended when susceptibility testing shows a
susceptible Gram-positive organism

• High rates of fluoroquinolone-resistant and extended-

spectrum β-lactamase (ESBL)-producing E. coli, initial
empirical therapy with an aminoglycoside or carbapenem
has to be considered until susceptibility testing demonstrates
that oral drugs can also be used
Recurrent UTI in female
Estimated 25% to 50% of women will suffer from
recurrences after UTI
• History to rule out
• Isolated / Recurrent UTI
• Reinfection / persistent infection
• Cystitis / pyelonephritis
• Complicated UTI
• STD
• Any positive culture
• Noninfective causes, e.g. CIS / stone
• Past medical history, e.g. DM
• Family history
• Pregnancy / menstrual status

• Physical examination
• Loin / suprapubic mass or tenderness
• Vaginal mass – prolapsed pelvic organ / estrogen status
• Neurological examination
 Workup of recurrent UTI

• Urinalysis and culture

• To confirm presence of recurrent UTI
• To determine bacterial persistence from reinfection
• Imaging studies
• Not routinely recommended in evaluation of women with
recurrent UTI
EAU 2010 Guidelines on UTI
• Rare to find significant abnormalities
Hooton et al Int J Antimicro Agents 17(2001) 259-68

March 2011
 Workup of recurrent UTI
• Further workup probably indicated in patients with
recurrent UTI AND :
• Gross hematuria
• Persistent microhematuria in between UTI
• Evidence of bacterial persistence
• Suspicion of complicated UTI
• Urea-splitting organism (urease +ve)
• Symptoms / signs of urinary tract obstruction (eg. ballottable mass,
palpable bladder)
Dielubanza et al Med Clin N Am 95 (2011) 27-41
Nickel et al Can J Surg. 1991 Dec; 34(6): 591-4

March 2011
 Risk factors for recurrent UTI
• Premenopausal women  Postmenopausal women
• Sexual intercourse  Estrogen deficiency
• Frequency  Urinary incontinence
• New partner  Presence of cystocele
• Use of spermicide and
 Large post-void residual urine
diaphragm
 Hx of UTI before menopause
• Pelvic anatomy (urethra-to-
anus distance)  Genetic factors
• Age of first UTI Raz et al Clin Infect Dis
• Family history (genetic factors) 2000;30:152-6
• Prior antimicrobial use
Scholes et al J Infect Dis
2000;182:1177-82

March 2011
 1: Age-related risk factors for rUTI in women [89,107,126]

Young and pre-menopausal women Post-menopausal and elderly women

History of UTI before menopause
Urinary incontinence
Sexual intercourse Atrophic vaginitis due to oestrogen
Use of spermicide deficiency
A new sexual partner Cystocoele
A mother with a history of UTI Increased post-void urine volume
History of UTI during childhood Blood group antigen secretory status
Blood group antigen secretory status Urine catheterisation and functional
status deterioration in elderly
institutionalised women
• Why are women at increased risk of recurrent
infection?
• Susceptibility to infections
• Increased number of receptors sites for
uropathogen
• Shorter urethra
• Close proximity to anus
• P blood group secretor / ABO blood group
non-secretor / Lewis non-secretor
• HLA-A3 phenotype
• What is pathogenicity?
• The ability of organism to cause disease
• What is virulence?
• Degree of pathogenicity
 What are the bacterial
virulence factors?
• Toxin, e.g. haemolysin
• Enzyme, e.g. urease
• Antihumoral factors, e.g. IgA inactiviting protein
• Adherence mechanism – afimbrial or fimbrial types (E.coli)
• Afimbrial adhesin – Dr adhesins
• Type P fimbriae (mannose resistant) have adhesions that bind to renal
urothelium and are associated with Pyelonephritis (>90%)
• Type P fimbriae are more virulent and more adhesive than type 1 fimbriae
• Type 1 fimbriae (mannose sensitive) binds to elements of bladder urothelium
and are associated with Cystitis
• Type 1 fimbriae are also referred to as mannose sensitive. Such an event is
inhibited by mannose
• S Pili – both bladder and kidney infection
• Penetration of host by schistosoma spine
• Intrinsic resistance of Proteus to Nitrofurantoin!!!
• Changed from fimbriae to afimbriae to evade phagocytosis
 What is normal host defence
mechanisms against UTI?
• Normal commersal flora of vaginal
• Lactobacilli reduced uropathogens to colonise by lowering
pH as a result of converting glycogen to lactic acid
• Normal antegrade flow of urine
• Vaginal oestrogen and IgA
• Normal exfoliation of urothelial cells
• Tamm-horsfall protein by ascending limb of loop of
Henle – bind type 1 pili
• GAG layer
• Osmolality, pH of urine
How to prevent recurrent UTI?
• Apply oestrogen to atrophic vagina to restore normal vaginal
environment and re-colonization with lactobacilli and reduce
recurrent UTI (Raz)
• Avoid the use of spermicides / diaphragms
• Antibiotics (Post-Coital / Self-start / Prophylaxis)

• Observe personal hygiene*

• Post-coital voiding*
• Hydration to maintain adequate urine output*
• *Never shown in case-controlled studies to be associated with
reduced risk of recurrent UTI i.e. not evidence-based
 How to prevent recurrent UTI?
• Continuous antibiotics (6-12 months, 95% reduction of recurrence, but
60% reinfected after stopping the antibiotics)
• Ciprofloxacin 125 mg, Septrin 480mg, trimethoprim 100mg,
cephalexin 250mg
• Nitrofurantoin 50 mg once daily – lower systemic absorption and
less microbial resistance, but avoided in pyelonephritis as tissue
level in kidney is low
• Avoid amoxicillin and cephalosporin which change fecal flora
• Postcoital antimicrobial prophylaxis
• Recurrent uncomplicated cystitis, self-diagnosis and self-treatment
with 3-day course regimen of an antimicrobial with MSU beforehand.
If failed > send MSU for proper culture
• Cranberry juice (Proanthocyanidin: 36 mg/Day) – block bacterial
adherence to urothelium, 20% ↓ Risk of infection
Bacteriuria
 What are the definitions of
significant bacteriuria?
• Kass first introduced quantitative microbiology in diagnosis UTI
• Significant bacteriuria of pyelonephritis in pregancy ≥ 105 cfu/mL of pure
growth
• However, miss 1/3 symptomatic UTI with growth ≥ 103 cfu/mLof pure growth
• 103 CFU/mL – Uncomplicated cystitis in women
• 104 CFU/mL – Uncomplicated pyelonephritis in women, catheter urine in
women, UTI in MEN
• 105 CFU/mL – Complicated UTI in women
• Asymptomatic bacteriuria should be treated in children, pregnant (20-40%
developed pyelonephritis) female and immunocompromized patents, or
prior to an invasive genitourinary procedure for which there is a risk of
mucosal bleeding, but not DM or elderly patient
• Bacteriuria is almost universal when the catheter is left in situ for longer than 3
days
 Should asymptomatic bacteriuria in
DM patients be treated?

• Double-blinded placebo-controlled study

• Treatment of asymptomatic bacteriuria does
not reduce complications in diabetic patients
• Concluded that screening and treatment of
asymptomatic bacteriuria in DM patients not
clinically indicated

Harding GK et al Manitoba Diabetes Urinary Tract Infection Study Group. Antimicrobial

treatment of diabetic women with asymptomatic bacteriuria. N Eng J Med 2002
Nov;347(20):1576-83
March 2011
UTI in pregnancy
 UTI
• Incidence of Male UTI – 1%, Female UTI – 5%
• Incidence of female UTI after menopause – 20%
• Asymptomatic bacteriuria in pregnancy: – ~5% (E-Coli)
• Treatment is necessary because of these 20-40% (~30%) develop
acute pyelonephritis, 2/3 have recurrence, usually in 3rd trimester
=> ↓30% to 1% if treated
• Complications associated with bacteria during pregnancy:
• Prematurity, Low birth weight, Prenatal mortality
• Pre-Eclampsia (7.6 fold)
• Obstetric intervention
• Higher chance of asymptomatic bacteriuria if previous UTI
• 2 MSU or 1 CSU >105 CFU/ml = Asymptomatic Bacteriuria
 Antibiotics in Pregnancy
• Safe for Pregnancy (Protect Mother + Child)
• Penicillin (Bactericidal => Interfere with Cell wall synthesis)
• Macrolides (Erythromycin: Bacteriostatic => - Ribosomal Protein Synthesis)
• Cephalosporins (Bactericidal => Interfere with Cell wall synthesis)

• Danger / Unsafe Antibiotics:

• Fluoroquinolone (Bacteriostatic: Prevent DNA replication) => All Trimesters:
• Toxicity to fetal cartilage and joints, Tendon damage
• Tetracycline (Bacteriostatic: - Ribosomal Protein Synthesis) => All Trimesters:
• Hepatotoxicity, deposit in teeth and bone
• Trimethoprim => Cotrimoxazole (*Septrin) (Bacteriostatic: Prevent DNA replication) Avoid in
1st trimester:
• Teratogenic and neonatal jaundice
• Aminoglycoside => Gentamicin (Bactericidal: - Ribosomal Protein Synthesis) => Avoid in 2nd
and 3rd trimesters:
• Can cross placental barrier => Used only for short periods for severe acute pyelonephritis
threatening maternal-fetal prognosis
• Nitrofurantoin => Avoid in third trimester:
• Hemolytic anemia and G6PD deficiency, hepatotoxicity, lung toxicity, inadequate urine
concentration if GFR < 50
• Chloramphenicol => Avoid in third trimester:
• “Grey-baby” syndrome
• Sulphonamide (Bacteriostatic: Inhibit Folate synthesis) => Avoid in 3rd trimester:

• Recurrent UTI in pregnancy – Cephalexin 125mg daily

 Acute pyelonephritis
• USG findings: focal or diffuse hyperechogenicity, thickening
of renal pelvis and ureteral dilation
• Higher risk if asymptomatic bacteriuria / VUR (correction of
VUR cannot prevent UTI during pregnancy) / history of renal
scarring
• Complications associated with bacteria during pregnancy
• Prematurity, low birth weight, prenatal mortality
• Pre-eclampsia (7.6 fold)
• Obstetric intervention
• Hospitalization and parental antibiotics
(Spontaneous renal rupture)

• No cause / upper tract obstruction / tumour

like AML
• Lumbar or abdominal pain / shock
• US : retroperitoneal hematoma
• JJ / PCN if obstruction
• Unstable hemodynamically: nephrectomy
Gentamicin
• Bactericidal – inhibit ribosomal protein synthesis
• (Diffuses into cytosol of bacteria and binds to bacterial
ribosomes, causing error in RNA translation into proteins,
and subsequent cell death)
• 3-7mg/Kg
• Check trough level and RFT before next dose
• <1mg/l > give the same dose
• 1-2mg/l > reduce the dose by 25% and check the level
before next dose
• 2mg/l > omit one dose and check the level
• Bad with Frusemide (increase nehrotoxicity)
• Can be used in patient with renal impairment with dose
modification
• Ototoxicity cause more commonly vestibular nerve
damage than deafness, or tinnitus
• Nephrotoxicity and impaired neuromuscular transmission
• Daily dose is usually used
• Increases bacterial cell kill
• Decreases bacterial resistance to Rx
• Less toxicity - toxicity of gentamicin is via a saturation
process
• Less expensive and more convenient
• Synergistic activity with beta-lactams and vancomycin
• Damage of cell wall by beta-lactams provide improved
access of aminoglycosides into bacterial cystosol
• Active against most GN organisms except Providencia,
Serratia
• Not active against GP organisms eg. Enterococcus, S
aureus
• Not active against anaerobes
• Completely excreted in urine
• Urine concentration 25-100x of serum concentration
• Urine half-life : 100 hrs
UTI in male
 What are the important points?
• Men should receive, as minimum therapy, a 7-day
antibiotic regimen
• Minimum treatment duration of 2 weeks is
recommended, preferably with a fluoroquinolone if
prostatic involvement
• Prophylactic antibiotics reduce the risk of bacteriuria
and septicemia by 65% and 75% respectively after
TURP
• Berry: Prophylactic antibiotics in TURP J Urol 2002
UTI in children
 What are the risk factors of UTI?
• Age
• Neonates and infants have increased bacterial colonization of the
periurethral area and an immature immune system, especially first
few weeks
• Vesicoureteric reflux
• Genitourinary abnormalities (pelviureteric or vesicoureteric
obstruction; ureterocele; posterior urethral valves)
• Voiding dysfunction (abnormal bladder activity, compliance, or
emptying)
• Foreskin. Uncircumcised boys have a 10-fold higher risk of UTI in the
first year due to bacterial colonization of the glans and foreskin
• Constipation
• Girls – 5%, Boys – 1%
• Male more common in UTI in first year
 What are the methods of urine
collection?
• Suprapubic bladder aspiration is the most sensitive
• Bladder catheterization is also a sensitive method,
even though there is the risk of introduction of
nosocomial pathogens
• Clean catch
• Urine collection after cleaning genitalia
• MSU
• Plastic bag attached to the genitalia
 What is the criteria of UTI?
• Pyuria (more than 10 leucocytes per field) and bacteriuria in
a fresh urine sample will reinforce the clinical diagnosis of
UTI
• Epithelial cells strongly suggestive on contamination
• WBC casts pathognomonic of pyelonephritis
 What are the types of UTI?
• Simple
• No temp, responds well within 48 hours, E-coli (responsible for
85% community acquired, 50% hospital acquired)
• Atypical – any of the following (NICE guideline)
• Seriously ill
• Poor urine flow
• Abdominal or bladder mass
• Raised creatinine
• Septicaemia
• Failure to respond to antibiotics in 48 hours
• Non-E-coli
 What is the clinical use of DMSA?
• For atypical and recurrent UTI
• Bound to the basement membrane of proximal renal
tubular cells
• A star-shaped defect in the renal parenchyma may
indicate an acute episode of pyelonephritis
• A focal defect in the renal cortex usually indicates a
chronic lesion or a ‘renal scar’ defects
• Defeat at 6 months is considered to be renal scarring
What is the antibiotic of choice for
severe UTI?
• Chloramphenicol, sulphonamides, tetracyclines
(because of teeth staining), rifampicin, amphotericin
B and quinolones should be avoided
• The use of ceftriaxone (Rocephin) must also be
avoided due to its undesired side effect of jaundice
• Aminoglycosides if necessary, serum levels should be
monitored for dose adjustment
UTI in renal impairment
What is the antibiotic in renal
impairment?
Catheter related UTI
What is the recommendation of catheter
insertion and choice of catheter?
 How to prevent catheter related
UTI?

Foley adjuncts for lowering biofilm formation:

- Biofilm => Conditioning Film (Surface of Foley / FB + Protein materials of body)
=> Attachment of Micro-organisms (E-Coli) onto the conditioning film
=> Bacterial replication and formation of Glycocalyx (Resist Abx penetration)
=> Form a colony of Micro-organisms and its extra-cellular product on the
surface of a FB / Foley / Stone, etc.

- Silicon Foley / Silver Alloy Foley (delay 1 week of Biofilm) / Abx Covered / JNC spray
What is the treatment of catheter
related UTI?
Sepsis
What are the definitions of
infection?
What are the definition?
 What is the pathogenesis of
sepsis?
• Heat stable endotoxin of G-ve bacteria is a lipo
(toxic) – polysaccharide (antigenic)
• Trigger release of mediators, like cytokine, activation
of kinin system, complement system and fibrinolytic
system
• Activation of white cell and macrophages
• Widespread microvascular injury, tissue ischemia
Photo

• This elderly woman complained of severe symptoms of cystitis of

sudden onset.
Q

• A. What abnormality is shown?

• Herpes zoster

• B. What are the typical cystoscopic appearances?

• Hemitrigonal vesicles