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Urinary Tract Urinary Tract InfectionInfectionDepartment of Nephrology,the First
Affiliated Hospital , Sun Yat-sun University
Qiongqiong Yang
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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