Urinary Tract Urinary Tract InfectionInfectionDepartment of Nephrology,the First

Affiliated Hospital , Sun Yat-sun University

Qiongqiong Yang

qqyzzm@yahoo.com.cn

Growth of >105 organisms per milliliter from a properly collected midstream “clean-catch ” urine sample

DefinitionsDefinitions

Dysuria frequency urgency

Anatomic categories:upper urinary tract infection ：Pyelonephritis

lower urinary tract infection ：Cystitis, urethritis

CategoriesCategories

urethra

Female Urinary System

bladder

ureter

kidney

uterus

Epidemiological categories:Catheter-associated Community-acquired

Symptomatic or not (Dysuria, frequency , urgency )• Symptomatic

• Asymptomatic

CategoriesCategories

EPIDEMIOLOGYEPIDEMIOLOGYGeneral population 0.91% incidence

Women 2.05%

Nonpregnant adult woman 5.0%

Pregnant women 7%

Elderly women 10%

Elderly men (>50yrs) 7.0%

infant 1.0%

School Girls 1-2%

School Boys 0.03%

*Data from 30,196 women

1st Affiliated Hospital of SunYat sen Uni

EPIDEMIOLOGYEPIDEMIOLOGY

USA:

Episodes of acute cystitis in female : 11% per year

Approximately 50%-60% of adult women report that they have had a UTI at some time during their life.

Acute cystitis : 36 million pts per year (18-75y); cost 16 hundred million $.

EtiologyEtiology

Microorgnisma: Bacteria, fungi, virus, Chlamydia trachomatis, Mycoplasma

The most common agents: the gram-negative bacilli.

Escherichia coli : 70% of acute

uncomplicated UTI

Staphylococcus saprophyticus :5%-15% in

young women

Proteus mirabilis, Klebsiella species,

enterococci or other uropathogens

Pathogenesis

Sources of infection

Predisposing factor

Local and systemic host

defense mechanisms

Pathogenicity of the stain

Ascending infection

Hematogenous infection

Lymphathic way

Bacteria gain access to bladder via urethra, or follow by ascent from bladder to renal parenchyma.

Sources of infectionAscending infectionAscending infection

bladder

urethre

Sources of infectionAscending infectionAscending infection

Staphylococcal species:

the vaginal introitus,

and distal urethra

Facilitated by the

factors such as sexual

intercourse,

contraceptive

(spermicide)

entrance

Enteric G(-) organisms: colonize on the rectal

introitus, the perurethral skin, and distal urethra

rectal introitusrectal introitus

Vaginal introitus Vaginal introitus Dital urethraDital urethra

Gender and sexual activity: Bacteriuia in women ： very common The female urethra:

colonization with colonic G negative bacilliAnatomy ： Proximity to the anus ； Short

length (-4cm) ； Its termination beneath the labia ( 唇）

Facilitating factors ： Sexual intercourse （ causing the introduction of bacteria into bladder ）

Bacteriuia in Male ： urethral obstruction by prostatic hypertrophy,

bacterial prostatitis Male <50 yrs old without history of sexual

rectal intercourse : uncommon

Predisposing factor

Obstruction: Obstruction: ((Hydronephrosis)

tumor, stricture, stone, prostatic hypertrophy

vesicoureteral reflux, Neurogenic bladder

dysfunction

Predisposing factor

Hydronephrosis

Dilation of ureter

ObstructionObstruction

Retrograde pyelograpy

Use of instrumentsUse of instruments ：： cystoscopy ， urethral

catheterization or indwelling urethral catheter MalformationMalformation and structural abnormalities and structural abnormalities ::

posterior urethral valve dysfunction Urethra or periurethral infection Urethra or periurethral infection ：： genital

infection ， bacterial prostatitis Renal parenchyma lesion ： DN ， Polycystic KD Poor immunityPoor immunity ：： use of immunosuppressive use of immunosuppressive

agentsagents ，， kidney transplantationkidney transplantation Defect of local mucous membrane of urethra

defense ability

Predisposing factor

Flushing effects of urine voiding

Antibacterial effects of urine: low pH, high osmolarity, high urea concentration

Antibacterial of the bladder mucosa: Secretion of organic acids and antibodies eg. IgA

Antibacterial of prostatic fluid

Barrier effect of sphincter of urethra

Local and systemic host defence mechanisms

Bacterial virulence factors

 E coli: specific O,K, and H serogroups

urethral stimulate symptom

dysuria (burning or discomfort on

urination), frequency

Infectious or noninfectious stimulate

Decreased volume of bladder

Disorder of cystic nerve function

Clinical Manifestation

Clinical Manifestation

Cystitisacute

pyelonephritisDysuria, frequency, urgency

obvious obvious

Fever, shaking chills

none showed

Costovertebral angles tenderness /sensitive to percussion

none showed

WBC mostly normal increased

pathogenic bacterium

Escherichia coli（ 75%)

coagulated negative

staphylococcus（ 15% ）

Escherichia coli 、 bacillus

proteus 、 Klebsiella

Clinical Manifestation

Asymptomatic bacteriuria Uncomplicated UTIs Complicated UTIs Recurrent UTIs Reinfection : different strains,

>1month, Cystitis Relapse: the same strain, <1month,

pyelonephritis

Complication

Bacteremia or Septicemia Papillary necrosis

DM, pregnancy, urinary obstruction Hematuria, pain in the flank or

abdomen, chills and fever, ARF Necrosis tissue is passed in the

urine Ring shadow on pyelography

Perinephric abscess

LaboratoryLaboratory testtest

Pyuria

Bacteriuria

Other ： WBC (leukocytosis) ， Erythrocyte sedimentation rate

(ESR) ， intravenous

pyelography(IVP) ， C-reactive

protein.

PyuriaPyuria

Urinary sediment of cleaning urine specimen : ≥5 wbc/HFP， ≥ 0.4 × 106 /hr; ≥ 1.0 × 106

/12hr ， WBC esterase test （ + ） WBC casts -Pyelonephritis

High sensitivity , but lower specificity （ 70% ） Leukorrhea contamination

sterile pyuira :

unusual infection such as tuberculosis, fungi,

chlamydia/mycoplasma infection

interstitial nephritis

BacteriuriaBacteriuria Suprapubic bladder aspirates : bacteria growth on the culture dish （ qualitative culture ， Golden standard ） Voided midstream “clean-catch” urine sample

Qualitative cultureColony countsColony counts （（ Quantitative culture ）

≥105 CFU[colony forming unit] /ml G+ ≥103 CFU /ml

104-105 CFU/ml suspicious, need reexamination 104 CFU/ml contaminative

significant

Unspun, clean-catchUnspun, clean-catch urine specimen urine specimen

Gram’s stain Gram’s stain

Bacteria can be seen /HFP 105/ml(95%)

Both sensitivity and specificity are 92%

Midstream “clean-catch” urine sediment

20 bacteria /HP

BacteriuriaBacteriuria

Chemical examination Nitrites test (Griess Test): nitric acid nitrous acid (G （ - ） bacilli ) sensitivity : 70.4%, specificity : 99.5%

Enteribacillus ： +Enterococcus ， staphylococci ， streptococcus faecalis ： -

Urine dipsticks  ：leukocyte esterase ， Griess Test Screening test

Gram negative bacilli. Escherichia coli Gram positive cocci in chains. Enterococcus faecalis

Gram positive cocci Staphylococcus saprophyticusGram positive budding yeasts and large pseudohyphae. Candida albicans

False bacteriuria should be False bacteriuria should be excludedexcluded

Urine samples were contaminated by leucorrhea, etc.

Urine sample was put at room temperature for more than 1 hr before inoculated.

Technical errors .

False negative in Urine culture

Use of antibiotics 7 days before culture. Frequency: Urine stayed in the bladder for

less than 6 hours; Water diuresis or recent voiding Disinfectant contaminating into urine

sample Anaerobe ， chlamydia ， fungi or other

microorganism infection.

Other examination WBC (leukocytosis) WBC (leukocytosis) Intravenous pyelography(IVP)Intravenous pyelography(IVP)

Recurrent UTIs ， complicated UTIs （ stone ）， Recurrent pyelonephritis ， unusual bacteria infections ， a history of UTI in pregnancy ， a history of childhood infections ， Male with UTI ， Painless Painless hematuriahematuria

Ultrasonic examination Renal tubule function Vesicoureteral reflux test during voiding

forbid toforbid to perform at acute perform at acute phase!phase!

DiagnosisDiagnosis

Patient with bacteriuria : diagnosed as UTI.

Colony counts ≥105 CFU ／ml （ midstream “clean-catch” urine cultures ） . For asymptomatic pts, urine cultures should be done twice, Each time colony counts ≥105 CFU ／ ml with same bacteria. G+ colony counts≥103 CFU /ml

BacteriuriaBacteriuria

Diagnosis

UTIUTI upper UTI acute pyelonephritis

lower UTI Symptoms and signs, pathogenic bacteria, tubule

function and leukocyte cast

cystitis

Systemic toxic symptoms ： T >38℃ ， WBC ， costovertebral angle tenderness/sensitive to percussion leukocyte castRecurrent within 4 weeks after ending the treatmentComplicated with obstruction or malformation, etcUnusual bacteria: Bacillus proteus Renal dysfunction IVP showing abnormal image .

Pyelonephritis

Review of 3 days therapyReview of 3 days therapy

No symptoms , pyuria, bacteriuria

NoninfectiousUrethral syndrome

Woman with urethral stimulate symptom

3 days antibiotics therapy （ TMP-SMZ 2#Bid / Ofloxacin 0.2g Bid ）

Urinalysis and urine bacteria culture

Cystitis (cured)

Symptoms relapse

with pyuria

and bacteriuri

apyelonephritis (occult )

pyuira

pyelonephritispyelonephritisUrethral syndromecaused by chlamydia trachomatis

7 days later

1W~1M

Without bacteriuira

With symptoms

Without symptoms

Yes No

Without bacteriuira

With bacteriuira

Differential Diagnosis

Systemic infection Diseases chronic pyelonephritis: pyelography or

ultrasonic examination Cortex scars and kidney pelvis /calices

deformed Renal size: asymmetric Tubuler dysfunction

Renal tuberculosis Urethral syndrome

Renal tuberculosis

The following Conditions should be The following Conditions should be suspected :suspected :

Chronic urethral stimulate symptoms Useless of antibiotics therapy Urine bacteria culture negative Pyuria, Aciduria Evidence of extrarenal tuberculosis:

Epididymis, spermatic cord or prostate tuberculosis

Renal tuberculosis

Confirmed diagnosisConfirmed diagnosis ：：(any one of the following three (any one of the following three

conditions can make a diagnosisconditions can make a diagnosis ））1. Clinical manifestation+ urine

tubercle bacillus culture positive.2. X-Ray indicated typical

manifestation of renal TB.3. Cystoscopy showed typical lesion of

cystitis TB.

Urethral syndrome

Infectious Urethral syndrome: Acute urethritis

mycoplasma or chlamydia

Azithromycin(1g in a single oral dose) , Doxycycline(100mg twice a day), Ofloxacin

Noninfectious Urethral syndrome: without pyuria and bacteriuria No antimicrobial treatment May related to dryness of the urethral and

vaginal mucosa in postmenopausal, estrogen-deficient women, psychological status such as anxiety

TreatmentTreatment

• Principles

• Treatment for different types of

UTIs

Principle(1)

Urine culture:

Who: Except in acute uncomplicated cystitis in women

When: before empirical treatment is begun.

How to use the culture results: antimicrobial sensitivity testing should be used to further direct therapy.

Principle(2)

Factors predisposing to infection should be identified and corrected if possible. obstruction and calculi

In general, uncomplicated lower UTIs respond to short courses of therapy(3 days), while upper UTIs require longer treatment(14 days).

Principle(3)

Antibiotics selection:

First chose antibiotics should be effective to G- bacilli

TMP and Fluoroquinolone can be used empirically as first line drug.

The presence of antibiotic-resistant strains should be suspected: in pts with repeated infections, instrumentation, or recent hospitalization, and antimicrobial sensitivity testing should be used .

Principle(4)

Therapeutic judgments:

Relief of clinical symptoms does not always indicated bacteriologic cure.

pt should be follow up at 2w and 6w after cessation of treatment.

A cure : resolution of symptoms and elimination of bacteriuria.

A failure: Presence of bacteriuria with or without symptoms .

Principle(5)

Therapeutic judgments:Recurrent infections should be

classified as Relapse: the same-strain occurring

within 2 weeks of the end of therapy. (an unresolved upper tract focus of infection ; persistent vaginal colonization)

Reinfection: recurrences > 2 weeks after the cessation of therapy with a new strain.

Treatment for different types of UTIs

Acute uncomplicated Cystitis in Acute uncomplicated Cystitis in womenwomen

Acute uncomplicated pyelonephritis Recurrent UTIs UTIs in Pregnancy UTIs in Male Catheter-associated UTIs Asymptomatic bacteriuria UTIs in Children

Acute uncomplicated Cystitis in Acute uncomplicated Cystitis in womenwomen

Common organisms: E coli or Staphylococus saprophyticus

single-dose therapy: Take the antibiotics for only one time with a

relatively large dose(SMZ （ SMX400g ， TMP80mg ）6 pills draught / Ofloxacin 0.6g draught).

more frequently relapse

3-days therapy:Eradicate vaginal and rectal flora colonization with E

coliTMP-SMZ 2# Bid / Ofloxacin 0.2 Bid

The best choice is 3 days therapy !

Acute uncomplicated Cystitis in Acute uncomplicated Cystitis in womenwomen

The short-term therapy should not be used Diabetes pts with the immunosuppressive therapy previous infections due to antibiotic-resistant

organisms UTI symptoms for >7 d UTI in pregnancy age>65yrs males with UTI ( urologic abnormalities or

prostatic involvement) Use of diaphragm

7- to 14 day regimen

CASE ICASE I CASE ICASE I

32 year-old woman History: dysuria , frequency and pain

on urination for 2 days gross hematuira for 1 day Physical: (-) Urinalysis: WBC+++ , RBC ++/HPF Lab Data: Isomorphic RBC

.

Diagnosis Bacteriuria?

Gram stain of unspun urine (x1000) showed an inflammatory cell and numerous Gram negative bacilli. Colony counts Escherichia coli ≥105 CFU ／ml （ midstream “clean-catch” urine cultures ） .

diagnosed as UTI.

Systemic toxic symptoms leukocyte cast

cystitis

3 days antibiotics therapy （ TMP-SMZ 2#Bid /

Ofloxacin 0.2g Bid ）

Review of 3 days therapyReview of 3 days therapy

No symptoms , pyuria, bacteriuria

Urinalysis and urine bacteria culture

Cystitis (cured)

7 days later

Without symptoms

Acute uncomplicated pyelonephritis

Antibiotics therapy: 14 days course Empirical treatment: Fluoroquinolone, the

third generation cephalosporin or aminoglycoside Sensitive to G- Bact. (E coli) Less nephrotoxicity and side effects High concentration in renal and urine. Intravenously the first few days, taking

orally 72 hrs after fever relieving.

Acute uncomplicated pyelonephritis

14 days antibiotics course

Acute uncomplicated pyelonephritis

Follow up at the 2nd

wk and 6th wks

Failure within 72 hr

relapse

Relief from symptoms without bacteriuria

Cured

Change ABs :•according to drug sensitive test• 6 wks’ ABs therapy

Change ABs :•according to drug sensitive test• 6 wks’ ABs therapy

predisposing factors:

predisposing factors:•unrecognized suppurative foci• calculi• urologic disease

•unrecognized suppurative foci• calculi• urologic disease

Recurrent UTIs

Bacteriuria reoccurs after cessation of treatment.

Reinfection : Cause by a different pathogen, usually occur 6 weeks after drug discontinuance . Cystitis

Relapse: the same strain, <2 wks, pyelonephritis

About 80% of the recurrent UTIs are reinfection.

Recurrent UTIs

A short-term antibiotics therapy initially. Follow-up: 1 or 2 wks after cessation

therapy. Relief without symptoms ,bacteriuia

and pyuria: Reinfection is indicated. The previous treatment was effective.

Failure to therapy:Antibiotic-resistant : change to a sensitive

ABs for a 7 days therapy Judgments the results of treatment

Recurrent UTIs

Judgments after therapy with a sensitive ABs for a 7 days therapy :

If the antibiotic works well: Reinfection If the antibiotic does not work: Relapse ,

same strain infectionpyelonephritisProlong treatment to 6 wks. If failed,

prolong the course.Check the predisposing factors

Recurrent UTIs

Recurrent frequently （ 2 times in half a year or 3 times in 1 year)

long-term ,low-dose antibiotics therapy (bacteriostasis).Daily or thrice-weekly administration of

a single dose of nitrofurantoin 50mg, TMP-SMX 80/400mg, ofloxacin 200mg per night after urinate

Half a year or may prolong to 1~2 yr

History of recurrent UTIs, with UTI symptoms

Short-term therapy

Review 7 days later

effective

reinfection sensitive antibiotics

Long-term low-dose antibiotics

failureeffective

failure

pyelonephritis

• 6 wks antibiotics therapy• Check the complicated factors

relapserecurrent UTIs frequenclyAntibiotic-resistent

Recurrent UTIs

Complicated UTIsComplicated UTIs

Presence of the predisposing factors: catheterization, instrumentation, urologic anatomic or functional abnormalities, stone, obsrtuction, immunosuppression, renal disease, or diabetes.

Hospital-acquired bacteria: E coli, klebsiella, Proteus, Serratia, pseudomonas, enterococci, and staphylococci. Antibiotic-resistent

Complicated UTIsComplicated UTIs

Empirical antibiotic therapy: Broad-specturm Imipenem A penicillin or cephalosporin PLUS an

aminoglycoside, or ceftriaxone or ceftazidime

Selected on the antimicrobial sensitivity pattern.

10-21 days Follow-up cultures 2-6 wks after cessation of

therapy.

Removal of catheter Short course of antibiotcs If the catheter cannot be removed:

Asymptomatic bacteriuia should be ignored.

The pt develops symptoms or in high risk of developing bacteremia: Replacement of the catheterSystemic antibioticChanging the drainage way if necessary (suprapubic cystotomy).

Catheter-Associated UTIsCatheter-Associated UTIs

UTIs in Pregnancy

Asymptomatic bacteriuria /Acute cystitis All pregnacy women should be screened

for asymptomatic bacteriuria during first trimester (4%-7%).

7 days of antibiotics therapy The incidence rate of premature delivery 、

low birth weight will increase if without treatment.

Antibiotics: low toxicity such as cephalosporin, Ampicillin, Amoxicillin.

UTIs in Pregnancy

Acute pyelonephritis

Parenteral antibiotic therapy

cephalosporin, or extended-spectrum penicillin.Urine culture should be performed to

ensure cure, and repeated monthly until delivery.UTIs in Pregnancy

Recurrent infection : continuous low-dose prophylaxis with nitrofurantoin.

Asymptomatic bacteriuria

Antimicrobial therapy is unnecessary in the Elderly pts.

Antimicrobial therapy is necessary: High-risk pts with neutropenia, renal

transplants, obstruction, or other complicating conditions

Preschool children 7 days of oral antibiotics therapy

initially

longer-term therapy(4-6 wks) in high-risk ptslonger-term therapy(4-6 wks) in high-risk pts

persistent asympomatic bacteriurapersistent asympomatic bacteriura

Monitoring without further treatment

Monitoring without further treatment

Prognosis

Uncomplicated UTIs : Complete resolution of symptom (>90%)

rarely progress to renal function impairment and chronic renal disease.

Complicated UTIs: develop to chronic pyelonephritis

difficult to cure unless correcting the predisposing factors.

Prevention

Drink more water Personal hygiene: pudendum cleaning for

female pts, redundant prepuce cleaning for male pts.

Avoiding using instruments as possible, and strictly following aseptic manipulation if necessary.

Vesicoureteral reflux: To establish a habit that void once again.

Prevention

Women with frequent symptomatic UTIs (3 per yr): Long term administration of low-dose Abs Avoid spermicidal use void soon after intercourse recurrent UTIs related to intercourse: The single dose of Abs can be used after

sexual intercourse.

Take Home Messages

Bacteruia and diagnosis of UTI Predisposing factors Complication of UTI Principles of therapy ,cystitis , and acute

pyelonephritis

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