Urinary Tract Infections (uti) & Prostatitis

Urinary Tract Infections & Prostatitis

Urinary Tract Infections (UTI’s)

Gisela I. Robles, Pharm. D. [email protected] PHA 6630: TP III February 12, 09

Learning Objectives Upon completion of this lecture, the student should have an understanding of the following facts about urinary tract infections (UTI’s) and prostatitis : • • • • • • •

Define the different types Describe the pathophysiology and etiology List common pathogens Recognize clinical features and presentation List the different diagnostic tools Recommend appropriate therapy Identify clinical pharmaceutical interventions

UTI Types •

•

Lower Tract – Infection in lower portion of UT. Can include bladder (cystitis), urethra (urethritis), prostate gland (prostatitis), and epididymitis. Upper Tract – Infection in upper portion of UT. Can include kidneys (pyelonephritis) and ureters.

UTI’s Background • UTI’s result from the presence of microorganisms in the urine (not related to contamination) that has the potential to invade the urinary tract and adjacent tissues • One of the most common bacterial infections (~ 8 million patient visits/year in the U.S.) • Prevalence: – Women > men while young – Women = men at the age of 65

• Localized vs. systemic

Male UT

UTI Types • Uncomplicated: Infection present in individuals with normal UT anatomy and no alterations in urine flow or voiding mechanism. • Complicated: Infection resulting from a predisposing lesion such as congenital abnormalities, distortion of UT, stone, indwelling catheter, prostatic hypertrophy and neurogenic deficits. Affect both genders similarly, and can involve the upper and lower UT. Men UTI’s are considered complicated.

UTI Pathophysiology

UTI Etiology • Bowel Flora • Uncomplicated UTI’s: – E. coli (85%)- MOST COMMON pathogen – S. saprophyticus (5 – 15%) – K. pneumoniae, Proteus spp., P. aeruginosa, and Enterococcus spp. (5 – 10%) – S. epidermidis- repeat cultures to r/o contamination

• Complicated UTI’s: – Pathogens w/ ↑ resistance to antibiotics – E. coli (< 50%) and E. faecalis (frequently isolated in hospitalized patients)

• Candida spp. • Single organism vs. multiple organisms • Community acquired vs. hosp. acquired

A. Route of entry: 1. Ascending 2. Hematogenous 3. Lymphatic B. Factors that impact infection development: 1. Size of inoculum 2. Virulence of microorganism 3. Natural host defense

– Obstruction • BPH • Urethral strictures – Caliculi – Tumors

• Incomplete bladder emptying

• Vesicoureteral reflux • Immunocompromised patients • Instrumentation • Pregnancy • Sexual intercourse / diaphragm use • Menopause

– – – – – – –

Low urine pH Extreme osmolality High [urea] High [organic acid] Prostatic secretions Micturition Anti-adherence mechanism: – Urinary mucus – Tamm-Horsfall protein

– Inflammatory response – Lactobacillus and estrogen levels

Clinical Presentation: UTI and Prostatitis

UTI Predisposing Factors • Age • Gender • UT structural abnormalities

C. Host Defense Mechanisms:

• Lower UTI • • • •

Dysuria Urgency/frequency Nocturia Suprapubic discomfort

• Upper UTI • • • • • • •

Fever Chills Malaise N/V Flank pain Abdominal pain Costovertebral tenderness

• Acute Bacterial Prostatitis • Perineal, sacral, or suprapubic pain • Urinary retention • Dysuria • Urgency/frequency • Nocturia

• Chronic Bacterial Prostatitis • Voiding difficulties • Perineal and suprapubic pain

Urinalysis

Laboratory Findings Parameter

•

Urine collection: • • •

• • • •

Midstream clean catch Catheterization Supra-pubic bladder aspiration

Urinalysis (dipstick for leukocyte esterase or nitrite, $ and fast) Urine microscopy (40x power) Urine Culture ($$ and lengthy) Bacterial susceptibility testing

Appearance

UTI Markers Cloudy

pH

Alkaline

4.5 – 8.5

Protein

Positive

Negative

Nitrite

Positive

Negative

Leukocyte esterase Positive

Negative

Positive

Negative

RBC WBC

>

Bacteria

Many

Finding

Symptomatic female

≥

Symptomatic male

≥ 103 CFU bacteria/mL

102

CFU coliforms/mL or ≥ 105 non coliforms/mL

Asymptomatic individual ≥ 105 CFU bacteria/mL X 2 specimens Catheterized individual ≥ 102 CFU bacteria/mL * Positive bacteria growth on supra-pubic catheterization in a symptomatic patient is considered a UTI.

Uncomplicated UTIs (Lower UTI) 1. Prevalence/Etiology: - Most common type - Sexual intercourse 2. Pathogens: - E. coli - S. saprophyticus - Klebsiella - Proteus 3. Clinical Presentation: - (+/-) dysuria, frequency, urgency and suprapubic discomfort

4. Antibiotics: - TMP/SMX - Nitrofurantoin - Fluoroquinolones 5. Duration of Therapy: - Conventional - Three-Five Day - Single Dose (one-day)

10/mm3

0 – 5 /hpf None

UTI Antimicrobial Treatment

Urine Culture Characteristic

Normal Values Yellow

A. • • • • B. • • • • • •

Goals: C. Duration of Therapy: Treat and prevent systemic infection • Conventional: Eradicate invading organism – 7-14 days (women) Prevent recurrent infections – 10-14 days (men) Prevent ADR • Short Course Antimicrobial Therapy: – Three-Five Day TMP/SMX , fluoroquinolones, – Single Dose nitrofurantoin and beta lactam agents • Recurrent/Prophylactic Susceptibility testing • Prostatitis Patient drug allergies Patient adherence Cost of therapy Refer to Antimicrobial Table (114-3) in Chapter 114, page 2087

Pyelonephritis (Upper UTI) 1. Prevalence/Etiology: - Complicated UTI 2. Pathogens: - Gram (-): E. coli, Klebsiella, Proteus - Gram (+): E. faecalis, S. saprophyticus - Long term hosp. patients: P. aeruginosa, enterococci and multiple-resistant pathogens 3. Clinical Presentation: - (+/-) dysuria, frequency, urgency and supra-pubic discomfort

Pyelonephritis (Upper UTI) cont’d 4. Antibiotics: - IV Antibiotics • • • • •

Calculate CrCl to determine appropriate antibiotic dose and frequency:

TMP/SMX (140-age) X IBW (0.85 if female) Fluoroquinolones (72 X SCr) Aminoglycoside +/- Ampicillin Aminoglycoside +/- Broad spectrum cephalosporin Beta lactamase inhibitors (i.e. Amp/Sulb, Tic/Clav, Pip/Taz)

- PO Antibiotics • TMP/SMX • Fluoroquinolones

5. Duration of Therapy: - Stop IV therapy after 3 day-treatment and patient clinical improvement, then start PO therapy X 2 weeks

Symptomatic Abacteriuria (Urethral Syndrome) 1. Prevalence/Etiology: - Fecal matter - Sexual intercourse 2. Pathogens: - E. coli - Staph spp. - Chlamydia trachomatis - Gardnerella vaginalis - Neisseria 3. Clinical Presentation: - (+) dysuria, pyuria and urine culture less than 105 bacteria/mL

Men UTI’s

Asymptomatic Bacteriuria 1. Prevalence/Etiology: – Most common in children, pregnant women, and elderly patients – Relapse and reinfection rates are high

2. Pathogens: – E. coli

3. Clinical Presentation: – No symptoms – Urine culture ≥ 105 bacteria/mL X 2 specimens

4. Antibiotics: – Controversial in elderly patients – Children and pregnant women SHOULD BE TREATED

1. Prevalence/Etiology: - Complicated - ↑ elderly patients - Instrumentation - Lack of circumcision - Sexual activity 2. Pathogens: - May vary when compare to women pathogens 3. Clinical Presentation: - Combination of lower and upper UTI symptoms

UTI’s During Pregnancy

Men UTI’s (cont’d) 4. Antibiotics: - Urine culture - Gram (-) coverage: TMP/SMX and fluoroquinolones (caution- ↑ risk for tendon rupture in those > age of 60, kidney, lung and ♥ transplant recipients and with concomitant steroid therapy) 5. Duration of Therapy: - Conventional ( 10 - 14 days)- Slightly longer than female conventional therapy - Short-course is CONTRAINDICATED - 2 week vs. 6 week therapy - F/U cultures

4. Antibiotics: - TMP/SMX - Fluoroquinolones - Azithromycin or doxycycline for chlamydia treatment 5. Duration of Therapy: - Short Course

1.

Etiology: – –

2.

Urinary stasis, ↓ defenses against bacteria reflux and ↑ [urine nutrients] Asymptomatic bacteriuria occurs in 4 to 7% of pregnant patients. Of these, 20 % - 40 % develop acute symptomatic pyelonephritis.

Pathogens: –

3.

E. coli

Screening: –

4.

Recommended at initial prenatal visit and 28 wks gestation

Antibiotics: – – –

Amoxicillin, amox/clav, cephalosporins or nitrofurantoin X 7 days Do not treat with TCN, sulfonamides, fluoroquinolones F/U culture in 1 – 2 weeks

Recurrent UTI’s

Catheterized UTI’s Risk Factors: • Duration of catheterization (> 30 days = ↑ risk) • Catheter system (closed drainage preferred) • Inappropriate care • Poor aseptic technique for catheter insertion • Patient susceptibility

Treatment Approach: • Asymptomatic patientRemove catheter • Symptomatic patientRemove catheter + conventional therapy • Prophylactic use of antibiotic for short-term catheter X 4 – 7 days • Bladder irrigation

Recurrent UTI’s Treatment • Postmenopausal women- topical estrogen • Antibiotic self-administration: • Postcoital (low-dose prophylaxis)- single dose of TMP/SMX, nitrofurantoin, cephalexin, or fluoroquinolone • Continued low-dose (long-term, low-dose prophylaxis) – < 3 infections/year: • Short course therapy per episode – ≥ 3 infections/year: • Treat each episode conventionally first • Prophylactic therapy second to prevent symptomatic infections X 6-12 months) • TMP/SMX, nitrofurantoin, fluoroquinolone (limit use secondary to ↑ drug resistance, adverse events, druginteractions and cost)

Adjunctive UTI Management and UTI Prevention • Shower instead of bathing • Avoid using any feminine hygiene sprays and scented douches • Avoid long intervals between urination • After urination, wipe from front to back • Empty your bladder after sexual intercourse

• Mostly re-infections (different pathogen) but also include relapses (same pathogen) • Relapse cases should be treated longer and follow up cultures are recommended • Classification: 2 infections/6 months, < 3 infections/year and ≥ 3 infections/year • Etiology • Sexual intercourse • Diaphragm and spermicide use

Adjunctive UTI Management and Prevention • Hydration • Cranberry juice (i.e. extract tablets 300 to 400 mg BID, CranMax 500 mg daily) • Lactobacillus • Topical estrogen • UT analgesics • phenazopyridine

UTI Assessment, Treatment & Prevention Checklist • Assessment: – Past medical history • Age related changes, co-morbidities, pregnancy, UT abnormalities, history of UTI or recurrent UTIs, medication allergies, urine culture susceptibility interpretation (if applicable) • Current list of medications

– Personal and social history • Catheter placement, home arrangement, shower vs. bathing

– Review of systems (physical exam): • • • •

General appearance (skin, hydration) Vitals Signs and symptoms of lower UTI vs. upper UTI Metal status changes (key presentation in elder patients)

UTI Assessment, Treatment & Prevention Checklist

• Assessment: – Urinalysis: • (+/-) pyuria, bacteriuria, nitrites, leukocyte esterase

– Others (for acutely ill patients): • • • • •

Lab. urinalysis w/ microscopic exam Urine C&S CBC with diff. Blood chemistry Blood culture

Prostatitis

A. Acute B. Chronic Bacterial

NIH Classification of Prostatitis • Category I – Acute Bacterial Prostatitis

• Category II – Chronic Bacterial Prostatitis

• Category III – Chronic Pelvic Pain Syndrome

• Category IV – Asymptomatic Inflammation

UTI Assessment, Treatment & Prevention Checklist

• Treatment: – Establish treatment goals based on diagnosis and presentation – Select antibiotic dose and therapy duration: • Consider renal function, drug interactions, urine C&S, medication compliance and cost

– Assess the need to treat fever, pain & dehydration – Educate patient about UTI prevention

Prevalence • ~ 60,000 ambulatory care visits by men over the age of 18 in the U.S./year • Young to middle age men • Symptoms include pain (testicles, penis, lower abdomen) bladder irritation, bladder obstruction, blood in semen and impotence

Acute Prostatitis • Microorganism way of entry – urethra • Risk factors: – – – –

Trauma Dehydration Sexual abstinence Chronic indwelling bladder catheters

Acute Prostatitis

• Presentation: – – – – – – –

Spiking fever Chills Malaise Dysuria Pelvic or perineal pain Cloudy urine Obstructive symptoms – dribbling and hesitancy to anuria

• Pathogens: – Gram (-), specially E. coli and Proteus spp.

• Complications: – – – – –

Bacterimia and sepsis Sacroiliac infection Epididymitis Prostatic abscess Chronic bacterial prostatitis

Acute Prostatitis Treatment • Non protein bound, lipophilic antibiotics (ideal but not required) • NSAIDs to relieve pain, inflammation, and liquefy prostatic secreations • Parental therapy can be switched to oral antibiotics alone after the patient has been afebrile for 24 to 48 hours • Duration of therapy: 4-6 weeks

Chronic Bacterial Prostatitis • Presentation include dysuria and frequency, urgency, perineal discomfort, low-grade fever, (+/-) prostate edema, and recurrent UTI in the absence of bladder catheterization • Gram (-) rods are the most common pathogens except for enterococci, Chlamydiae, and Mycobacterium tuberculosis • Diagnosis can be made by analyzing specimens obtained following prostatic massage for leukocytes and bacteria

• Diagnosis: – Edematous and tender prostate at digital exam – Urine gram stain – Blood cultures – Leukocytosis – ↑ Serum prostate antigen (PSA) levels

Acute Prostatitis Treatment • Gram (+) pathogens: – Cocci in chains (enterococcal) – • Oral – amox. 500 mg q8h • IV – amp. 2 g q6h

– Cocci in clusters (staphylococcus) – • Oral – cephalexin 500 mg q6h; dicloxacillin 500 mg q6h • IV – cefazolin 1g q8h; nafcillin 2 g q6h; vancomycin 1 g q12h (MRSA/PCN allergy)

• Gram (-) pathogens: – Oral – TMP/SMX one DS q12h; fluoroquinolone (ciprofloxacin 500 mg q12h and levofloxacin 500 mg daily) – IV – aminoglycosides (gentamicin or tobramycin 5 mg/kg q24h) PLUS ciprofloxacin or levofloxacin

Chronic Bacterial Prostatitis • Chlamydia infection: – Involve the epididymis and urethra – Can reside in the prostate tissue rather than invasion of urethral contaminants

• Treatment duration: 6 to 12 weeks • Fluoroquinolones and TMP-SMX reach [therapeutic] in prostate tissue

Chronic Bacterial Prostatitis Treatment • For first and recurrent episodes, ciprofloxacin 500 mg q12h or levofloxacin 500 mg daily

Patient Cases

• For Chlamydia infection, azithromycin 500 mg daily vs. 1 g once

Patient Case

“Yearning and Burning”

JM Clinical Presentation • PMH:

JM is a 21 y.o. woman who presents to the University Health Center with dysuria. She reports having increased urgency and frequency of urination that began the night before.

Patient Case : UA Results Parameter Appearance

Finding Cloudy, red/orange

pH

5

Protein

10 mg/dL

Nitrite

Positive

Leukocyte esterase

Negative

RBC

1 – 5 cells/hpf

WBC

10 – 15 cells/hpf

Bacteria

Many

UTI 6 mo ago treated with TMP/SMX for which she developed a rash after finishing tx.

• SH: Smokes ½ ppd, (+) marijuana use, social ETOH, sexually active (multiple partners).

• ROS: (-) vaginal discharge, bleeding, fever, or chills. (+) pain during urination • Med ALL: TMP/SMX • Current Meds: – Ortho-Novum 7/7/7- 1 po QD – Phenazopyridine100 mg po prn

1. What type of UTI this pt has? A. Complicated, upper, recurrent, asymptomatic UTI B. Complicated, lower, recurrent symptomatic UTI C. Uncomplicated, upper, recurrent, asymptomatic UTI D. Uncomplicated, lower, recurrent, symptomatic UTI

2. Which of the following is a potential pathogen? A. B. C. D.

S. aureus P. aeruginosa E. coli C. trachomatis

4. What should be the therapy duration? A. B. C. D.

1 day 3 days 14 days (2 weeks) 21 days (3 weeks)

6. What could include a future treatment approach for multiple recurrent UTIs? A. B. C. D.

Self antibiotic administration Postcoital antibiotic administration Continued low-dose antibiotic therapy All of the above

3. Which of the following antibiotics could be considered for treatment? A. Ciprofloxacin B. Amoxicillin C. TMP/SMX

5. At this point in time, should this patient receive prophylactic antibiotic therapy? A. YES B. NO

7. Should a urine culture be obtained from this patient experiencing her 2nd episode of cystitis? A. YES B. NO

Case # 2 A medical resident calls the ambulatory care pharmacist regarding the use of a fluoroquinolone in a 24 y.o. semi professional soccer player with an apparent UTI. She has complained of dysuria and frequency for the last 24 hours. Her UA is positive for bacteria using a nitrate dipstick and WBC’s using a dipstick esterase test. Her past medical history is significant for DM. She has no allergies and other than her diabetes there has been no other significant medical problems.

Case # 2 • What type of UTI this is?

Case # 2 • What additional information do we need from this patient?

Case # 2 • Patient education:

• Is a fluoroquinolone agent a good option for this patient? • What are other antibiotic alternatives?

Case # 3 A consultant pharmacist is contacted about a 72 y.o. woman nursing home patient. She recently was treated for 10 days with ceftriaxone and azithromycin for presumed CAP. During her hospitalization a foley catheter was placed. She is currently afebrile and asymptomatic of any UTI symptoms but a culture of her urine at the end of her antibiotic therapy had a significant growth of yeast. How should she be managed?

Case # 3

• How should this patient be managed?

Acute and Chronic Prostatitis: Review • Pathogen • Recommended therapy • Duration of therapy

References • Potoski BA. Urinary Tract Infection. In Chrisholm-Burns MA, Wells BG, et al, eds. Pharmacotherapy: Principles and Practice. New York, NY:McGraw Hill; 2008:1151-1158. • Urinary Tract Infection. In Dipiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy, A pathophysiologic Approach. 6th ed. New York, NY:McGraw Hill; 2006:2087.