Urinary Tract Infection

Prevalence
Community-dwelling

elders 25%

Long-term

care elders (chronically bacteriuric)

25-50% of women 15-40% of men

Marked

increases in women & men after age 65

Urinary Tract Infection Defined

Definition Women: Presence of at least 100,000 colonyforming units (cfu)/mL in a pure culture of voided clean-catch urine Presence of just 1,000 cfu/mL indicates urinary tract infection

Men:

*Some labs do not routinely identify & determine the sensitivity of organisms for specimens with <10,000 cfu/mL. May have to special request.

Urinary Tract Infection

Urinary

tract infectionmost common source of bacteremia, a dangerous systemic infection in long-term care facilities times more likely to occur in catheterized than non-catheterized residents
leads to significant morbidity and mortality in the vulnerable elderly

Bacteremia40

Bacteremia

Urinary Tract Infection Physiologic Changes

Physiologic changes with aging in the urinary tract Age-Related Changes Decreased bladder capacity and increased urine production (especially at night) Decreased voided volume Decreased estrogen w/menopause leads to thinning of vaginal & urethral mucosa Decreased lower urinary tract sensory threshold Men Women

UTIPhysiologic Changes
Physiologic changes with aging in the urinary tract Age-Related Changes Men Women

Problems of urinary storage & emptying

incidence of overflow incontinence from urethral obstruction or stricture Decreased estrogen levels leads to pH changes in vagina, favoring colonization of E. coli, risk of UTI

Prostatic enlargement can lead to urinary obstruction, increased residual urine & infection

Age-Related Changes in the Urinary System

Structure
Glomeruli

Change
number surface area

Impact
filtration of blood glomerular filtration rate by 30-40%

Tubules

thickened membrane fatty degeneration shortening

stiffening narrowing expandability & compressibility of bladder

tubule

transport urine-concentrating capacity Na conservation renal acidification

blood flow efficiency in removal of waste product

Renal vasculature

Connective tissue

bladder capacity residual urine volume after voiding

History & Physical Examination

Age-related Risk Factors for UTI

Advanced Age Fecal incontinence/impaction Incomplete bladder emptying or neurogenic bladder Vaginal atrophy/estrogen deficiency Pelvic prolapse/cystocele Insufficient fluid intake/dehydration Indwelling foley catheter or urinary catheterization or instrumentation procedures

H & P, contd
Age-related Risk Factors for UTI Diabetes or immunosuppression Benign prostatic hypertrophy Bladder or prostate cancer Urinary tract obstruction Spinal cord injury

H & P, contd
Female vs. Male Complicating Factors
Age Group Female (years) Risk Factors 50-70 Estrogen deficiency Diabetes Gynecological diseasescystocele & related surgical procedures Male Risk Factors Prostatic obstruction Diabetes Urological/surgical procedures

H & P, contd
Female vs. Male Complicating Factors
Age Group (years)
>70

Female Risk Factors

Estrogen deficiency Diabetes Gynecological diseases (cystocele & related surgical procedures) Urological diseases (incontinence, residual urine, cystopathy) & related surgical procedures Urinary catheter Reduced mental status Co-morbid diseases Immunological changes

Male Risk Factors

Prostatic obstruction Diabetes Urological/surgical procedures Urinary catheter Reduced mental status Co-morbid diseases Immunological changes

Symptoms versus Asymptomatic Bacteriuria

Asymptomatic Bacteriuria (ASB) Defined as the presence of bacteria in urine of patients who do not have dysuria, urinary frequency, urgency, fever, flank pain, or other symptoms related to irritation of the urethra, bladder, or kidney Strictly definedexists when 2 urine cultures done with clean-catch specimens are positive in a patient who has no urinary tract symptoms

Symptomatic vs Asymptomatic Bacteriuria, contd

ASB Frequent in elderly elderly >70 yrs old women: 16-18% men: 6%

Symptomatic vs. Asymptomatic Bacteriuria, contd

Asymptomatic Bacteriuria (ASB) Most ASB in the elderly is associated with complicating factors such as: Hormonal: post-menopausal women Anatomical: prostatic obstruction in men, cystocele in women Functional: CNS, i.e.dementia Metabolic: diabetics (ASB females with Type 2 diabetes29%) Immunological: s in inflammatory mediators (cytokines, acute phase proteins) Instrumental: indwelling catheteralways bacteriuric symptoms

UTI Signs and Symptoms in Elderly

Very difficult to assess and recognize, even when present in the older adult. Signs & Symptoms that indicate further evaluation for UTI elicited from H&P:

New or increased urgency, frequency, dysyuria: > in younger patients, still can be present in elderly These complaints can be common & chronic without bacteriuria Requires careful interpretationmay not be due to UTI Change in character of urine One study found cloudy, bloody, or malodorous urine in >85% symptomatic UTIs Others less predictive

Signs and Symptoms, contd

Clarity of urine
Clear no bacteria; cloudy, milky or turbid bacteriuria Cloudiness, however, can occur in normal urinemucus, epithelial cells Cloudy character, alone or with (+) dipstick analysis further lab analysis Study by Loeb et al. (2001) as consensus criteriacloudy urine not an indication for antibiotics Bloody Hematuria not always indicative of infection; possibly irritation or medication related Malodorous Not a valid indicatormay be caused by bacteria, but could be hygiene-related Often considered an indicator, however

Signs and Symptoms, contd

Elevated temperature(vital signs)
Elderly require > time to present with fever, may not have any increase in temperature may even be hypothermic Elderly at d risk for masked or absent fever response due to antipyretics, corticosteroids, chemo Rx, alcoholism, hypothyroidism, malnutrition and renal insufficiency Studies indicate fever is a marker for serious infection & most important clinical indicator for antibiotic treatment Other studies, fevers can resolve without treatment; antibiotics did not improve outcomes in elderly Not always due to UTIconsider differential diagnoses: pulmonary or skin infections Lack of fever may delay diagnosis

Signs and Symptoms, contd

Pain Despite limitations of assessment in the elderly, suprapubic, flank or CVA pain can indicate UTI (abdominal, rectal & vaginal exam) Agitation, irritability, restlessness, decreased appetite, increased confusion, or even falls may indicate pain (Neuro & GI exam) Cultural differences in interpretation of pain, symptoms Incontinence May be caused by UTI or the altered mental status that occurs with the elderly Commonly caused by other conditions Symptom and a risk factor of UTI

Signs and Symptoms, contd

Other Possible Signs & Symptoms of UTI Signs of sepsis other than fever or decline in M.S. Hypotension Tachycardia Tachypnea Rales Respiratory distress Anorexia, nausea, vomiting Abdominal tenderness

Causative Pathogens
UTI in Women Escherichia coligram (-) etiologic agent in ~ 80% of all = UTIs Research indicates primary source of microbial invasion is retrograde colonization by intestinal pathogens Other factors influencing colonization: vaginal pH, urethral length, capacity of bacteria to adhere to urothelium

Complicated vs Uncomplicated UTI

Recurrent UTIsculture-confirmed UTIs * >3 in 1 year or * > 2 in 6 months Relapse UTI occurs within 2 weeks of Rx of an earlier UTI same pathogen occurs >4 weeks after earlier UTI different pathogen

Re-infection UTI

Screening/Diagnosis
Infectious Disease Society of America: Guidelines for Dx & Rx of ASB in adults
1. ASB Dx based on results of a culture from clean-catch specimen (* important to minimize contamination) Women: bacteriuria = 2 consecutive voided urine samples w/isolation of same strain in cfu/mL >100,000 Men: bacteria = single, clean-catch specimen with 1 bacterial species isolated in > 100,000 cfu/mL Both: single catheterized urine specimen with 1 bacterial species isolated in a count of > 1,000 cfu/mL

Screening/Diagnosis
Guidelines, continued

2.
3.

4.

Pyuria accompanying ASB not an indication for antimicrobial Rx (A-2) Pregnant women should be screened in early pregnancy, at least once & treated if positive (A-1) Screening of ASB & Rx if positive before these urological procedures: Transurethral resection of prostate (A3) Procedures anticipated to cause possible mucosal bleeding (A-3)

Screening/Diagnosis
Guidelines, continued 5. No screening for ASB: (A-1 & A-2 strongly recommended via research evidence) Pre-menopausal, non-pregnant women (A-1) Diabetic women (A-1) Community older adults (A-2) Institutionalized elderly (A-1) Spinal cord injury (A-2) Indwelling-catheterized patients (A-1) 6. Antimicrobial Rx of asymptomatic women with catheteracquired bacteriuria persisting 48 hrs after removed, should be considered (B-1/good) 7. No screening or Rx of ASB renal transplant or solid organ transplant recipients (C-3/weak)

Screening/Diagnosis Guidelines, continued

Guide to Clinical Preventive Services, 2005 Similar consensus of IDSA recommendations Clinical considerations Dipstick analysis & direct microscopy have poor positive & negative predictive value for detecting ASB Urine culture = gold standard, but expensive for routine screening in populations of low prevalence New enzymatic urine screening test (UriscreenTM) showed 100% sensitivity & specificity of 81% No clinical benefit to screen individuals other than pregnant womendid not improve clinical outcomes. Guide to Clinical Preventive Services, 2005 http://www.ahrq.gov/clinic/ppcletgp/geps2b.htm#bacteriaria

Screening & Diagnosis

Guideline Criteria for Treatment
The following are a recommended minimum set of criteria adapted from the McGeer (1991) and Loeb et al. (2001) studies necessary to initiate diagnostics and AB Rx.

Indwelling catheter present: two of the following must be met

Fever

Catheter is not present: three of the following must be met

Acute

(>38C/100.4F) or increase of 1.5C (2.4F) above baseline temperature. Chills New costovertebral angle tenderness New suprapubic pain, flank pain or tenderness Decreased mental or functional status (delirium) New-onset hematuria, foul-smelling urine, or amount of sediment

dysuria alone (key indicator) or fever (>38C/100.4F) or increase of 1.5C (2.4F) above baseline temperature Chills Frequency Urgency New costovertebral angle tenderness Decreased mental or functional status (may be new or increased incontinence related) *
New-onset

hematuria, foul-smelling urine or (+)

sediment New suprapubic pain, flank pain or tenderness

Laboratory Analysis, continued

Routine UrinalysisKey Indicators of Infection
Urine collection 1st morning specimen is best Straight catherization for those incontinent, functionally or cognitively impaired

Specific gravity
Appearance

Measure of kidneys abiltiy to concentrte urine Range of SG depends on state of hydration

Cloudy, may not indicate WBCs Could indicate a change in urine pH causes precipitation Alkaline urine phosphates cloudy Acid urine urates cloudy Pale yellow to amber Variations can be caused by medications, disease processes (*nl urine darkens on standing 30 min. after voidingoxidation of urobilinogen to urobilin) nl faint odor when freshly voided Foul-smellingoften presence of bacteria which splits urea to form ammonia

Color

Odor

Laboratory Analysis, continued

Routine Urinalysis, continued
pH Acid or basemeasures free H+ ion concentration in urine 7.0 neutral. Indicates kidney function Determines if systemic acid-base disorders of metabolic/resp. origin control of pH manages bacteriuria, renal calculi & drug Rx bacteria from a UTI produce alkaline urine

Blood or Hemoglobin
Protein (Albumin) Microalbuminuri a

Always an indicator of kidney/UT damage

Single most important indication of renal disease Below dipstick range of detection Detects deteriorating renal function in diabetic patients (standard screener)

Laboratory Analysis, continued

Routine Urinalysis, continued
*Nitrite (Bacteria) Dipstick - rapid, indirect method to detect bacteria common gram-negative organisms contain enzymes reduce nitrate in urine to nitrite some UTIs are caused by organisms that do not convert nitrate to nitrite (e.g., staphylococcus, streptococci) Esterase is released by leukocytes (WBCs) in urine Microscopic exam & chemical test

*Leukocyte Esterase

__________ *U/A testing positive for nitrite & leukocyte esterase should be cultured for bacterial pathogen Fischbach, 2004

Urine Culture and Sensitivity

Traditional gold standard for significant bacteriuria >100,000 cfu/mL of urine. Some argue criteria for bacteriuria is only 100 cfu/mL of a uropathogen in symptomatic females or 1,000 in symptomatic males. Bacterial identification from urine C&S, key in males and females with complicated UTIs.

Other Laboratory Tests

Complete Blood Count with Differential Indicated to R/O bacterial infection supports treatment plan Careful evaluation of WBC & differential (left shift) Electrolytes R/O dehydration & if IV fluids replacement needed BUN, Creatinine Determine renal function for nephrotoxic medications Blood Culture Identify bacteremic organism in suspected urosepsis

Treatment Plan
Early detection/Rx goal is to prevent systemic infection, bacteremia Initiation of antibiotic treatment is recommended for a clinically-diagnosed UTI. Adjust medication when urine C&S is final Selection of antibiotic must be individualized and consider: Side effect profile Cost Bacterial resistance Likelihood of compliance (convenience, fewer pills/day s compliance) Effect of impaired renal function on dosing Possible adverse drug reactions in elderly (multiple drugs, co-morbidities.

Treatment Plan
Recommended Treatment Regimens for Acute, Uncomplicated UTIs in the Elderly
Treatment
Sulfonamide TrimethoprimSulfamethoxazole TMP-SMX

Dosage/Duration
160/800 mg po bid x 3-14* days *available in a syrup If CrCl <15-30 mL/min, in half

Bacterial Coverage/ Resistance

(E. coli 20%) resistance Less effective

Common Side Effects

nausea, rash

Compliance/ Convenience
Fair/Good longer duration of bid compliance

Cost I/E
I

Men

Women

Fluoroquinolones Ciprofloxacin (2nd gen)

Levofloxacin (3rd gen)

100- 250 mg po bid x 3-14* days If CrCL <30mL/min by half

250 mg po daily x 10 days (complicated upper and lower UTI) 3 g powder, dissolved in water *single dose

gram (-) effective gram (+) only fair

headache, dizziness, nausea, diarrhea

Good/Good bid, longer duration compliance Excellent

Fosfomycin

gram (-) effective gram (+) less effective

diarrhea, vaginitis, nausea, rhinitis

Excellent

VE, often not on formularies I

Nitrofurantoin (Macrobid)

100 mg po bid x 7 days If CrCL <40 mL/min not recommended

Narrow spectrum gram (-) effective gram (+) effective

nausea, vaginitis, diarrhea rate of severe pulmonary & hepatotoxicity PCN-anaphylaxis Abdominal cramping diarrhea

Fair 7-day regimen & bid, compliance

Prostatitis NR

Miscellaneous Beta Lactam ABs: Cephalosporins (Cefuroxime, cefpodoxime) Penicillins (ampicillin), Carbapenems (imipenem) Phenazopyridine (Pyridium)not appropriate for elderly or patients with renal insufficiency

resistance 2 Beta Lactamase enzymes in resistant bacteria 2nd/3rd gen Cephalosporins >resistant to beta lactamase

Fair for bid dosing

Prostatitis NR

Data adapted from Swart et al. (2004), Osborne (2004), Wagenlehner et al. (2005), MahanButtaro et al. (2006) and Evercare Corp (2004) I = inexpensive; E = expensive; VE = very expensive; NR = not recommended
*Longer duration for complicated UTI per individuals clinical status

Prevention & Treatment Recommendations/Considerations/Prevention

Research Studies
Wilde & Carrigan (2003)
Muder et al. (2006)

Findings
Patients with indwelling catheters, maintaining urine flow was a key finding in preventing UTI
Urinary

catheterization is a major risk factor for S. aureus bacteriuria in long-term care patients, so reducing prevalence of indwelling catheters is key. Majority of these cases are methicillin-resistant S. aureus, which can lead to bacteremia Need for optimal infection-control measures & limit unnecessary AB admin. in LTCF. Focus on urine as potential infection reservoir, may be effective preventive strategy Study focused on catheter-related UTI. Catheter infection rate of 5%/day *Formation of biofilm on catheters leads to infection as this protects pathogens from antimicrobials & host immune response Studied efficacy of antimicrobial urinary catheters in hospitalized patients. prevent or delay onset of catheter-associated bacteriuria

Nicolle ( 2005)

Johnson et al (2006)

Prevention & Treatment

Recommendations/Considerations/Prevention
Post-menopausal women w/recurrent infection may require estrogen replacement to restore atrophic vaginal mucosa, vaginal pH (topical creams) Always adjust antibiotic dosage for renal impairment/insufficiency using the Cockcroft-Gault equation: (140-Age) x weight in Kg x 72 x serum creatinine X Ensure adequate hydration Recommended 2.5 L/day in patients with recurrent UTI Often signs & symptoms similar to UTI in elderly are actually caused by dehydration (0.85 if female)

Bakteriuria Asimptomatik pada Kehamilan Prevalensi 2-10% BAS th/ antibiotika u/ mencegah pielonefritis dan komplikasi kehamilan.
Bakteriuria Asimptomatik pada DM Wanita > pria Hubungan fx resiko gangguan faal kandung kemih dg peningkatan kepekaan terhadap ISK pada DM.

Infeksi Saluran Kemih

Adanya mikroorganisme dalam urin dengan atau tanpa gejala klinik dan dengan atau tanpa penyakit ginjal Bakteriuria bermakna menujukkan pertumbuhan mikroorganisme > 105 colony forming units (cfu/ml) pada urin Piuria bermakna ditemukan netropil > 10 /lapang pandang

Terms
Urinary tract infection Significant bacteriuria Asymptomatic bacteriuria Acute pyelonephritis Chronic pyelonephritis Upper versus lower UTI Urethral syndrome

Infeksi Saluran Kemih Bawah

Perempuan - Sistitis infeksi kandung kemih disetai bakteriuria bermakna - Sindroma Uretra Akut (SUA) presentasi klinis sistitis tanpa ditemukan mikroorganisme (steril). MO anaerobik Laki-laki - Sistitis, prostatitis, epidimidis, uretritis

Infeksi Saluran Kemih Atas

Pielonefritis Akut (PNA) proses inflamasi parenkim ginjal yg disebabkan infeksi bakteri Pielonefritis Kronis (PNK) akibat lanjut infeksi bakteri berkepanjangan atau infeksi sejak masa kecil. Obstruksi saluran kemih dan refluks vesikoureter dengan atau tanpa bakteriuria kronik sering disertai pembentukan jaringan ikat parenkim ginjal pielonefritis kronik yang spesifik. Bakteriuria asimptomatik kronik pasien dewasa tidak pernah jaringan ikat parenkim ginjal.

Predisposisi ISK
Litiasis Obstruksi Saluran Kemih Penyakit Ginjal Polikistik Nekrosis Papilar Diabetes mellitus pasca transplantasi ginjal Nefropati analgesik Penyakit Sikle cell Senggama Kehamilan dan peserta KB dengan tablet progesteron Kateterisasi

Mikroorganisme saluran kemih

Escherichia coli >> infeksi asimptomatik/ simptomatik Proteus sp 33% ISK anak Laki-laki usia 5 th Klebsella sp Stafilococcus Pseudomonas spp

PATOFISIOLOGI ISK
Uretrodistal kolonisasi mo nonpatogenik gram + dan ISK>> invasi mo asending dari uretra kandung kemih ginjal, dipermudah o/ refluks vesikourinaria Invasi mo hematogen << akibat lanjut bakteremia Ginjal lokasi infeksi akibat lanjut septikemia atau endokarditis k/stafolococcus aureus Nephritis Lohlein kel. Ginjal terkait endokarditis (stafilococcus aureus) PNAakibat lanjut invasi hematogen dan infeksi sistemik gram negatif.

KLINIK ISK
Pielonefritis Akut : Panas tinggi (39,5-40 derajat Celcius), menggigil, sakit pinggang, dapat diawali ISK bawah(sistitis) ISK bawah (sistitis) : sakit suprapubik, polakisuria, nokturia, disuria, stranguria Sindrom Uretra Akut(SUA) : sulit dibedakan dengan sistitis. >> pada wanita usia 20-50 th. Disuria dan sering kencing disertai kuman < 10 5 sistitis abakterialis SUA dapat terbagi 3 kelompok

 SUA dibagi 3 kelompok : 1. Piuria diisolasi E.coli cfu/ml urin 10 3-10 5. Infeksi berasa dari kel. Periuretral atau uretra. Respon baik ampisillin 2. Leukosituria dg 10-50/lpb tinggi dan kultur urin steril . Biakan khusus chlamydia trachomatis atau bakteri anaerobik 3. Tanpa Piuria dan biakan urin steril.
ISK rekuren 1. Re-infeksi interval >6 mgg dg mo yg berlainan. 2. Relapsing infection. mo yg sama th/ tidak adequat

Komplikasi ISK
1. ISK sederhana( uncomplicated) ISK akut tipe sederhana(sistitis) non obstruktif dan bukan perempuan hamil penyakit ringan (self limited disease).Tidak menyebabkan akibat lanjut jangka lama . 2. ISK tipe berkomplikasi (complicated) ISK kehamilan selama kehamilan ISK pd DM >> bakteriuria dan ISK pada DM dibanding wanita tanpa DM

Morbiditas ISK Selama Kehamilan

Kondisi BAS tidak diobati Resiko potensial Pielonefritis Bayi Prematur Anemia Pregnancy-induced hypertensiom Bayi mengalami retardasi mental Pertumbuhan Bayi lambat Cerebral Palsy Fetal death

ISK trimester III

BAS : Basiluria asimptomatik

 BAS resiko pielonefritis LFG. Komplikasi : emphysematous cystitis, pielonefritis yg terkait kandida dan infeksi gram negatif lainya dapat pada DM. Piolenefritis emfisematous mo pembentuk gas seperti E.coli, Candida spp, klostridium DM. Pembentukan gas intensif pd parenkim ginjal dan jaringan nekrosis disertai hematome yg luas. >> disertai syok septik,nefropati akut vasomotor (AVH)
Abses perinefritik komplikasi ISK pada DM(47%), nefrolitiasis (41%), obstruksi ureter (20%)

Pemeriksaan Penunjang ISK

Analisa Urin rutin Pemeriksaan urin segar tanpa putar Kultur urin Renal imaging procedures : - USG - Radiografi : poto polos perut, pielografi IV, Micturating cystogram Isotop scanning

Penatalaksanaan ISk
ISK Bawah - intake cairan yg >>, antibiotika adequat, th/simptomatis untuk alkalinisasi urin. - Ampisilin 3 gram, trimetroprim 200 mg tunggal , 80% memberikan respon setelah 48 jam. - Infeksi menetap th/konvensional 5-10 hari - pem. Mikroskopik urin dan biakan urin tdk diperlukan bila semua gejala hilang dan tanpa leukosituria

 Reinfeksi berulang (frequent re-infection) - + fx predisposisi Th/ antimikroba yg intensif koreksi fx resiko - Tp fx predisposisi - Asupan cairan banyak - Cuci setelah senggamaantimikroba tunggal(m/trimetroprim 200 mg) - Th/ antibiotika jangka lama sampai 6 bulan. SUA hitung kuman 10 3- 10 5 antibiotika adekuat. Klamydia respon dg tetrasiklin.Infeksi mo anaerob m/quinolon.

 Infeksi Saluran Kemih Atas - Pielonefritis akut rawat inap u/ memlihara status hidrasi dan terapi anbiotika pareenteral sedikitmya 48 jam. - the infection Disease Society of America 1 dari 3 alternatif th/ antibiotika IV sbg awal terapi slm 48-72 jam sebelum diketahui mo penyebab: 1. Fluorokuinolon 2. Aminoglikosida dg atau tanpa ampisilin 3. Sefalosporin dengan spektrum luas dg atau tp aminoglikosida

Indikasi Rawat Inap Pasien dengan Pielonefritis Akut

Kegagalan un tuk mempertahankan hidrasi normal atau toleransi terhadap antibiotika oral Pasien sakit berat atau debilitas Terapi antibiotika oral selama rawat jalan mengalami kegagalan Diperlukan investigasi lanjutan Faktor predisposisi untuk ISK tipe berkomplikasi Komorditas seperti kehamilan, DM, usia lanjut