URINARY TRACT INFECTION : Clinical Practice Guidelines

YOUR LECTURER : 

    

among the most common infections encountered > 7 million office visits and 250,000 hospital admissions for pyelonephritis annually in the USA 1-3% of schoolgirls ; increase markedly after adolescence with onset of sexual activity vast majority of acute symptomatic UTI involve young women account for 5 to 17% of consultations at OPD clinics in Manila, Cavite & Davao 40% of hospital-acquired infections 

IMPLICATIONS: 

Financial ±  Community acquired UTI = $1.6 billion per annum  Nosocomial UTI = > $400 million Medical ±  

Bacteremia Symptoms 



Pregnancy : pyelonephritis, prematurity, fetal complications and mortality, preeclampsia Pediatrics : impaired renal function, renal scarring, ESRD 

ENDEND-STAGE RENAL DISEASE IN THE PHILIPPINES
Leading causes of ESRD among dialysis patients Philippine Renal Disease Registry 1998 UTI, 11%

(complicated type i.e. stone dse.)

HTN, 14% DM, 22% GN, 39% 500 1000

CLASSIFICATION AND UROPATHOGENESIS OF URINARY TRACT INFECTION

Urinary Tract Infection 


Lower tract infection (acute cystitis, urethritis) Upper tract infection (acute pyelonephritis & other renal infections) Nosocomial (usu. Catheter-associated) CatheterCommunityCommunity-acquired 



Uncomplicated (normal host; rare sequelae) (normal sequelae)  Complicated (deep-seated infection with obstruction (deepor instrumentation; frequent recurrences and sequelae) sequelae) 

THE URINARY TRACT INFECTION SYNDROMES
Asymptomatic Bacteriuria Acute Uncomplicated Cystitis in Women Acute Uncomplicated Pyelonephritis UTI in Pregnancy Recurrent UTI Complicated UTI Uncomplicated UTI and Prostatitis in Males

Source: Philippine Clinical Practice Guideline on the Diagnosis And Management of Urinary Tract Infection ± Report of the Task Force on Urinary Tract Infections

Dysuria!

Significant Bacteriuria (>105/ml) 

Delineates the anatomical site of infection Cystitis: superficial mucosal infection Pyelonephritis: deep tissue infection in the renal medulla  

Lesser Colony Counts 2 4.9 (10 to 10 / ml)
May be contamination by distal urethral or vaginal flora 

Clues:

pyuria and isolation of single species uncontaminated by normal vaginal or urethral flora superficial mucosa of bladder and urethra 

Site:

Host Factors
Urinary tract is anatomically united by a continuous column of urine from urethra to kidney. 
female > male: short urethra colonization by coliforms, urethral trauma during sex  catheterisation  pregnancy  vesico-ureteric reflux vesico poorly controlled diabetes mellitus  elderly men (prostate)  bladder dysfunction (spinal injuries, MS)  obstruction: urethral stricture, stones, tumors

Bacteriuria Risk Factors
Study conducted in predominantly white (90%) college women 

  

Sexual intercourse is a major risk factor for UTI Use of diaphragm increases the risk of bacteriuria Urination after sex reduces risk of symptomatic UTI Use of oral contraceptives does increase the risk of UTI, but this is attributable to increase in sexual activity in the users  Other factors WITHOUT effect on UTI  urination before sex  frequency and method of cleaning  direction of wipe after bowel movement

Bacterial Adherence and Other Virulence Factors for Urinary Tract Infection  

Bacterial attachment does not occur unless bacterial fimbriae or other surface adhesion systems are present. Bacterial virulence is not related to resistance to antimicrobial drugs. Bacterial adhesion onto mucosal or urothelial cells 
 

general phenomena determining bacterial virulence infection in urinary tract = directly related to the ability of bacteria to adhere & then to colonize first in the gut & then sequentially in the perineum, urethra, bladder, renal pelveocalyceal system & renal interstitium

Organisms
‡ Escherichia coli - 80-90% community acquired 80‡ Proteus - urease alkaline urine stones ‡ Enterococcus faecalis ‡ Klebsiella, Enterobacter, Serratia, Citrobacter - common in hospitals ‡ Pseudomonas spp. - common in hospitals (catheters, antibiotic resistance) ‡ Chlamydia trachomatis, N.gonorrheae, Herpes simplex ± young and sexually active ‡ Candida sp./ fungal - catheter, diabetes mellitus ‡ Adenovirus - rare, young children, ' hemorrhagic cystitis' ‡ Staphylococcus saprophyticus aureus - rare (after bacteremia), diabetes ‡ Mycobacterium tuberculosis

ESCHERICHIA COLI
Uropathogenecity of E. coli : virulence factors  Presence of adhesions on bacterial fimbriae (pili)  Nature of fimbriae ` Type I fimbriae = promotes infection & increases the inflammatory response ` Dr fimbriae = prevents clearance of infection  Presence of flagella  hemolysin production  Resistance to plasma bactericidal properties
or renal cell

NonNon-Infectious Causes of Isolated Pyuria
‡ Vesicoureteral reflux ‡ Analgesic nephropathy ‡ Uric acid nephropathy ‡ Polycystic kidney ‡ Acute tubular necrosis ‡ Transplant rejection ‡ Allergic interstitial N ‡ Sarcoidosis ‡ Hypercalcemic nephropathy ‡ Lithium toxicity ‡ Hyperoxalosis ‡ Heavy metal toxicity ‡ Carcinoma of bladder ‡ Renal calculi ‡ Sickle cell disease ‡ Idiopathic interstitial cystitis

³ PYURIA per se does NOT automatically mean UTI. ´

Asymptomatic Bacteriuria
‡ Definition: Presence of > 105 cfu/ml of one or more uropathogen on 2 consecutive midstream urine specimens or on one catheterized urine ; in the absence of symptoms attributable to UTI ‡ Screening: Urine culture recommended in diabetics, pregnancy, patients who will undergo genitourinary manipulation, or after removal of prolonged catheter

Asymptomatic Bacteriuria
Treatment may be indicated in certain subgroups at risk of high morbidity, i.e., 
   

patients undergoing urinary tract manipulation pregnancy renal failure valvular heart disease and prosthetic valves Immunocompromised (e.g. HIV, chemo, DM, KT)

³ Every elderly and bed-confined patient should not be treated because bedof the futility of maintaining a sterile urine and the emergence of resistant organisms with treatment ´

Acute Uncomplicated Cystitis
Definition: Clinical illness due to inflammation of bladder epithelium and/or urethra as a result of bacterial infection, with typical growth of u 100 colony - forming units (cfu)/ml of midstream urine in non pregnant women (18 - 50 yrs old), presenting with: a) any of the ffing symptoms: dysuria, frequency, urgency, hematuria or hypogastric pains b) without symptoms of vaginitis, pyelonephritis & risk factors for subacute pyelonephritis or complicated UTI

Laboratory Diagnosis of Acute Cystitis
Presence of significant pyuria :
a) 8 or more pus cells /mm3 of uncentrifuged urine b) 5 or more pus cells /hpf of centrifuged urine c) positive leukocyte esterase & nitrite test 
Pre-treatment urine culture and sensitivity is NOT Prerecommended  Standard urine microscopy & dipstick leukocyte esterase & nitrite tests are also not prerequisite for treatment

Treatment of Acute Cystitis 
3 - day course of antimicrobial therapy is effective. However, patients should be advised to come back if symptoms persist or recur

Choice of Antibiotics: 3 day regimen ‡ ‡ ‡ ‡ ‡ ‡ ‡ TMP/SMX Nitrofurantoin Ciprofloxacin Norfloxacin Pefloxacin Ofloxacin CoCo-Amoxiclav 160/800 mg BID 100 mg QID 250 mg BID 400 mg BID 400 mg BID 200 mg BID 375 mg TID

Acute Uncomplicated Pyelonephritis
Definition: Fever (> 38oC), chills, flank pain, costovertebral angle tenderness, nausea & vomiting, with or w/o signs & symptoms of lower U.T.I., in an otherwise healthy female with no clinical or historical evidence of structural or functional urologic abnormalities.

Acute Uncomplicated Pyelonephritis
Laboratory findings: pyuria (u 5 wbc/hpf of centrifuged urine) (u bacteriuria with counts of u 10,000 cfu of a uropathogen / ml in culture of voided urine Etiologic Diagnosis: 
Gram stain of uncentrifuged urine  Urine C/S  Blood C/S (done twice)

Acute Pyelonephritis
Indications for admission: inability to maintain oral hydration or take medications  concern about compliance  uncertainty about the diagnosis  severe illness with high fever, severe pain, marked debility & signs of sepsis
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Treatment of Acute Pyelonephritis
Characteristic Pathogens
E. coli, P. mirabilis, K. pneumoniae S. saprophyticus

Clinical Situation
Mild-to-moderate illness, no nausea or vomiting, - outpatient therapy Severe illness or possible urosepsis -hospitalization required

Recommended Empiric Treatment
Oral* fluoroquinolone, TMP/SMX or co-amoxiclav for 14 days

Parenteral** aminoglycoside, fluoroquinolone or third generation cephalosporin until fever is gone (usually after 24 - 48 hrs), then oral fluoroquinolone or TMP/SMX to complete 14 days

*Oral regimens: ciprofloxacin 500 mg or ofloxacin 400 mg or norfloxacin 400 mg or TMP/SMX 160-800 mg, all every 12 hrs; and Co-amoxiclav 625 mg every 8 hrs. Ciprofloxacin may be given for 7 days. **Parenteral regimens: ceftriaxone 1 - 2 g once a day; ciprofloxacin 200 - 400 mg every 12 hrs; ofloxacin 200 400 mg every 12 hrs; gentamicin 3 - 5 mg/kg once a day or 1 mg/kg every 8 hrs.

Acute Uncomplicated Pyelonephritis
FollowFollow-up cultures during & post-therapy: post‡ No need for follow-up cultures followif responding well, < 72 hrs ‡ Recurrence of symptoms require genitogenito-urologic evaluation ‡ For those who relapse with the same strain as the initially infecting strain, a 4 - 6 weeks regimen is recommended

RELAPSE
Recurrence of bacteriuria w/ original infectinginfecting-organism within 2 wks of stopping therapy ; failure to eradicate bacteria from GUT

REINFECTION
Recurrence of bacteriuria with a new organism caused by entry of bacteria into the bladder from the fecal-perineal reservoir fecal-

RECURRENT U.T.I.
more than 2 reinfection episodes in a year; may require cost-effective costprophylaxis with low-dose antibiotic low-

Three preventive strategies for Recurrent UTI : ‡ Acute self-treatment with 3-days of standard self3therapy. ‡ Postcoital prophylaxis with cotrimoxazole (400/80mg) if the UTIs are clearly related to intercourse. Alternatives are antibiotics below. ‡ Continuous daily prophylaxis up to 6 months: ‡cotrimoxazole 400/80 mg ‡nitrofurantoin 50 to 100 mg ‡norfloxacin 200 mg ‡cephalexin 250 mg ‡ciprofloxacin 125 mg

COMPLICATED UTI
Definition:
Significant bacteriuria in setting of immunocompromised state or functional/anatomic abnormalities of the urinary tract or kidneys:

‡ Indwelling urinary catheter (5% infection rate per day) ‡ Urologic abnormalities
± ± ± ± Bladder retention > 100ml of urine postvoid Obstructive uropathy by stones, tumor or BPH Azotemia due to intrinsic renal disease Vesicoureteral reflux

‡ ‡ ‡ ‡

Diabetes mellitus Renal transplantation Neutropenia AIDS

Uropathogens in Complicated UTI :
Type of Complicated UTI
CatheterCatheter-assoc. UTI ‡ Short term (< 1wk) ‡ Long term

Uropathogen

E.coli, Pseudomonas aeruginosa Proteus mirabilis, Enterobacter Usually polymicrobial ± Pseudomonas, E.coli, Providencia, Morganella, Citrobacter, Enterococcus, Candida E.coli, Kleb.pneumoniae (37%), Ps.aeruginosa, Proteus mirabilis E.coli, Kleb.pneumoniae, Proteus mirabilis, Enterobacter, Candida, Ps.aeruginosa, Candida

Urologic abnormalities UTI in Diabetics

Uropathogens in Complicated UTI :
Type of Complicated UTI
Renal Transplant

Uropathogen

E.coli (30-60%), Proteus mirabilis & (30Kleb.pneumoniae (30%), gm(+) cocci (20%), Enterobacter, Enterococcus, Serratia, Acinetobacter, Citrobacter, Ps.aeruginosa Gm(Gm(-) bacilli esp. Pseudomonas Staphylococcus aureus, Candida E.coli, Kleb.pneumoniae, Proteus mirabilis, Enterobacter, Candida, Ps.aeruginosa, Enterococci, Staph, CMV, Adenovirus, Toxoplasma, Pneumocystis, Mycobact.TB

Neutropenic Patients

UTI in AIDS

Empiric Antibiotic Regimens for Complicated UTI 

Choice of Antibiotics:

14 day regimen Oral regimen (mild cases): Ciprofloxacin 250 mg BID Norfloxacin 400 mg BID Ofloxacin 200 mg BID Cotrimoxazole 800 mg BID Parenteral regimen (mod.-severe cases) : (mod.Ampicillin 1 gm q 6h IV + Genta 3-5 mkd IV 3Ceftazidime 1-2 gm q 8h IV 1Ceftriaxone 1-2 gm OD IV 1Imipenem 250-500 mg q 6-8h IV 2506Ciprofloxacin 200-400 mg q 12h IV 200Ofloxacin 200-400mg q 12h IV 200-

Antibiotics should be modified according to urine CS result. Oral switch therapy done once afebrile or clinically improved after 48hrs

UTI in pregnancy
Incidence of up to 8% * in pregnant women Physiologic changes in pregnancy relates to increased susceptibility to UTI¶s : 
  

Progesterone effects causes relaxation Blood volume expansion Increased cardiac output and renal plasma flow Chemical changes in urine (more alkaline) due to respiratory alkalosis

* Mikhail MS. Obstet Gynecol Survey 1995;50:675-83 1995;50:675-

Urinary System Changes 
 

ureterovesical reflux incontinence (pelvic floor weakness) frequency (bladder compression)

Urine Culture in Pregnancy : 
obtained in first prenatal visit or between 12 ± 16 weeks of gestation (Grade A) *  gold standard for bacteriuria (105 cfu/ml)  also obtained during the third trimester **  cost-effective prevention of pyelonephritis in preg. cost repeat urine culture after 1 week post-treatment postis appropriate
* U.S. Preventative Services Task Force. 2nd ed. Baltimore: Williams and Wilkins 1996 * * American College of Obstetricians and Gynecologists bulletin no. 245, March 1998

Types of UTI in Pregnancy : 
Asymptomatic bacteriuria (ASB)  Acute Cystitis  Pyelonephritis

Pyelonephritis in Pregnancy 

Antibiotics are the same as in acute uncomplicated pyelonephritis, except when contraindicated :

SAFE IN PREGNANCY Cephalosporins -Cephalexin 1 gm qid IV x 3-5 days 500mg tid po x 9-11d Cefuroxime 750mg tid IV x 3-5 days 250mg bid po x 9-11 d Cephradine 1gm qid IV x 3-5 days 500mg tid po x 9-11 days Ceftriaxone 1-2 gm IV od x 14 days Co-Amoxiclav 1.2 gm tid IV then 625mg tid po Ampi/Sulbactam 1.5 gm qid IV then 750mg bid po Aztreonam 500mg ± 1gm bid-tid IV USE WITH CAUTION Aminoglycoside gentamicin 3-5mg/kg od IV ;or 1mg/kg tid IV Trimeth/Sulfa 160/800mg bid IV / po (1st & 2nd trimester only) CONTRAINDICATED Fluoroquinolones / Tetracyclines Trimeth/Sulfa (3rd trimester)

UTI in AL ‡ considered complicated ‡ uncomplicated: 1st episode, lower tract, 15-40 yrs 15old, healthy, sexually active, normal GUT ‡ otrimoxazole or luoroquinolone x 7 days ‡ prostatitis
± acute: ever, low back and perianal pain, malaise and postration, irritative voiding symptoms, tender prostate ± chronic: relapsing recurrent UTI ± dx: prostatic secretions >10 WB /hp ± treatment
‡ acute: cotri or oral luoro x 30 days ‡ severe: IV, urology re erral ‡ chronic: cotri or luoro x 2-3 mos, TURProstatectomy 2-

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