Urinary Tract Infections (UTIs)

Urinary Tract Infections

Definition and Prevalence

• Urinary Tract Infection (UTI): Presence of microorganisms in the urine not accounted for by contamination.

• Prevalence varies by age and gender.

• Symptomatic UTI: Occurs in 30% of women between 20-40 years old.

• Up to 50% of females will have a UTI at some point in their lifetime.

Types of UTIs Based on Location

Upper UTI

• Types of Infections:

  • Pyelonephritis

  • Intrarenal abscess

• Presentation:

  • CVA tenderness

  • Flank pain

  • Fever

  • Nausea/Vomiting (N/V)

  • Malaise

Lower UTI

• Types of Infections:

  • Cystitis

  • Urethritis

  • Prostatitis

  • Epididymitis

• Presentation:

  • Dysuria (painful urination)

  • Urgency

  • Frequency

  • Nocturia (frequent urination at night)

  • Suprapubic heaviness

  • Gross hematuria (visible blood in urine)

Uncomplicated vs. Complicated UTIs

Uncomplicated (Simple) UTI

• Involves only one type of bacteria.

• 85% are caused by E. coli.

• Limited to the lower urinary tract.

Complicated UTI

• Structural or functional abnormality interferes with urine flow or host defenses.

• Factors include:

  • Congenital abnormalities

  • Obstruction

  • Indwelling catheters

  • Neurologic deficits affecting urinary function

  • UTIs in males

• Require longer treatment regimens.

• Often polymicrobial (involving multiple bacteria).

• Patients are more prone to additional UTIs.

Laboratory Tests and Routes of Infection

Laboratory Tests

• Urine Analysis (U/A) Possible Findings:

  • Pyuria (pus in urine)

  • Nitrite

  • Leukocyte Esterase

  • Blood

Routes of Infection

• Ascending:

  • Bacteria from the urethra travel up to the bladder, causing cystitis.

  • More common in females (shorter urethra).

  • Most common route of infection for UTIs.

• Other Routes:

  • Hematogenous:

    • Seeding of the urinary tract with pathogens from the bloodstream.

  • Lymphatic

Host Defense Mechanisms and Risk Factors

Host Defense Mechanisms

• Urine characteristics: low pH, high osmolality, and urea.

• Prostatic secretions: can inhibit bacterial growth.

• Increased urge to urinate when bacteria enter the bladder.

Risk Factors

• Female

  • Sexual Intercourse, lack of voiding after sexual intercourse

  • Use of diaphragm and/or spermicide

  • Diabetes Mellitus

  • Pregnancy

• Male

  • Uncircumcised

  • Prostatic hyperplasia

• Both Sexes

  • Urologic instrumentation

  • Neurogenic bladder

  • Urinary tract obstruction

  • Incomplete voiding

UTI Treatment

Treatment Goals

• Eradicate causative organism.

• Prevent complications and recurrence of infection.

Treatment Considerations

• Patient compliance.

• Drug properties: Adequate concentration in urine.

Treatment Duration

• Uncomplicated: 1-7 days (3 days is optimal).

• Complicated: 2-4 weeks (up to 6 weeks if prostatic involvement).

Empiric vs. Directed Treatment

• Uncomplicated UTIs: treated empirically (without Culture & Sensitivity (C&S)).

• Complicated UTIs: Gram stain, Culture & Sensitivity (C&S) with empiric treatment until results return.

Treatment of Uncomplicated UTI

Acute Uncomplicated Cystitis

• Frequent presentation in the outpatient setting.

• Especially common in women of childbearing age.

Causative Organisms

• E. coli > 85% of uncomplicated lower UTIs.

• Other causes:

  • Staph Saprophyticus

  • Klebsiella Pneumoniae

  • Proteus Mirabilis

  • Enterococcus spp.

• Empiric treatment with coverage for the most common organisms.

• Follow up for resolution of signs/symptoms.

Treatment Duration

• Single-dose treatment – not recommended.

• 3-7 days.

• 3 days is optimal with good cure rate & avoidance of Adverse Effects (AE’s).

Antimicrobials for Uncomplicated UTIs

Nitrofurantoin (Macrobid®)

• MOA: Inhibits various enzymes in bacteria and damages DNA

• AE: hemolytic anemia (G6PD deficiency), GI, acute pneumonitis, neurological problems

• Contraindications: anuria, oliguria, pregnancy ≥ 38 wks

Dosing: 100mg PO BID x 5 days.

• Do not use in patients with Creatinine Clearance (CrCl) < 60ml/min.

Trimethoprim/Sulfamethoxazole (TMP/SMX) (Bactrim DS, Septra DS®)

• Dosing:

  • 2 Double Strength (DS) tablets as a single dose.

  • 1 DS tablet BID x 3-7 days.

• AVOID in sulfa allergic patients.

• In some areas, there is up to a 20% resistance rate.

Fluoroquinolones

• Ciprofloxacin (Cipro®) 250 mg BID x 3-7 days.

• Levofloxacin (Levaquin®) 250 mg Qday x 3-7 days.

Fosfomycin (Monurol®)

• 3gm PO x 1

• Mechanism of Action (MoA): inactivates pyruvyl transferase which then inhibits bacterial wall synthesis = bactericidal.

• Adverse Effects (AEs): anorexia, diarrhea, epigastric discomfort, Headache (HA), Nausea (N), Vomiting (V), rash.

Beta-Lactams

MoA: Interfere with bacterial cell wall synthesis/repair. Bind penicillin binding proteins (PBP)

weakens cell membrane → cell lysis → bactericidal. Exhibit time dependent killing

AE: GI Upset, Hypersensitivity reactions, Nephritis, Neurotoxicity

Amoxicillin: 3 grams x 1 dose or 500 mg BID x 3 days.

• Amoxicillin/Clavulanate (Augmentin®): 500 mg Q8h x 3 days.

• Cephalosporins: good efficacy but no advantages in simple UTI over Augmentin®.

• Big push to avoid fluoroquinolones for uncomplicated UTIs due to increasing resistance in Staph, Pseudomonas, and other strains of bacteria.

Antimicrobials for Complicated UTIs

Trimethoprim/Sulfamethoxazole (TMP/SMX) (Bactrim, Septra DS®)

• Dosing: 1 DS tablet BID x 7-14 days.

Fluoroquinolones

• Ciprofloxacin (Cipro®) 250-500 mg BID x 7-14 days.

• Levofloxacin (Levaquin®) 250 mg Qday x 7-14 days.

Amoxicillin/Clavulanate

• Dosing: 500 mg Q8h x 7-14 days.

Recurrent Lower UTIs

• Nitrofurantoin

  • Dosing: 50 mg Qday x 6 months.

• TMP/SMX

  • Dosing: ½-1 single strength tablet Qday x 6 months.

Acute Pyelonephritis

Signs/Symptoms

• Fever/chills, malaise, flank pain, CVA tenderness, N/V, decreased appetite.

Treatment

• Many of the same antimicrobials used for uncomplicated UTIs.

• Gram stain.

  • Gram Stain: gram (+) cocci: S. fecalis (Ampicillin indicated).

• Empiric therapy until Culture and Sensitivity (C&S) results.

• Fluoroquinolones or Aminoglycoside +/- Beta-lactam.

• Longer Duration of Treatment: Usually 14 days.

Inpatient vs. Outpatient Treatment

• Inpatient: IV Antimicrobial & IV Fluids.

  • High fever, N/V & high risk of dehydration, immunocompromised.

Antimicrobials for Acute Pyelonephritis - Outpatient

First-Line Therapy

• Fluoroquinolones

  • Ciprofloxacin (Cipro®) 500 mg BID x 7 days.

  • Levofloxacin (Levaquin®) 750mg Q day x 5 days.

• Ceftriaxone IV, gentamicin IV - if Fluoroquinolone (FQ) resistance >10%.

Second-Line Therapy

• TMP/SMX (Bactrim, Septra DS®)

  • Dosing: 1 DS tablet BID x 14 days.

• Ceftriaxone 1gm IV.

• Gentamicin 7mg/kg IV.

• Amoxicillin/Clavulanate

  • Dosing: 500 mg Q8h x 14 days.

UTIs in Special Populations: Pregnancy

• Pregnancy: UTIs are more common.

• Associated with adverse fetal effects.

• Asymptomatic bacteriuria may progress to pyelonephritis.

• Treat to avoid complications.

• Regular screening for bacteriuria during pregnancy.

Treatment Options in Pregnancy

• First-Line Treatment (Tx): Beta-Lactams

  • Amoxicillin or Amoxicillin/Clavulanate (Augmentin®) - if increased resistance to Amoxicillin.

  • Cephalosporins - Cephalexin (Keflex).

• Sulfonamides: AVOID in 3rd trimester (newborn hyperbilirubinemia).

• AVOID Tetracyclines & Fluoroquinolones IN PREGNANCY.

• Follow up urine culture: 1-2 weeks after completion of therapy.

UTIs in Special Populations: Catheterized Patients & Males

Catheterized Patients

• UTIs are very common in catheterized patients.

• Bacteria may be introduced into the bladder with insertion of the urinary catheter, or bacteria may ascend to the bladder.

  • Asymptomatic: remove catheter & hold antimicrobials.

  • Symptomatic: remove catheter & antimicrobials.

• If discontinuation of the catheter is not possible, change the catheter (especially if > 2 weeks).

UTIs in Male Patients

• Abnormality (structural or functional) should be expected.

• Treat as complicated UTI.

• Treatment duration: 7-14 days (longer if prostate involvement).

Recurrent UTIs

• Two groups based on number per year:

  • < 3 UTIs per year: treat each infection with short-course therapy.

  • 3 UTIs per year: consider long-term prophylactic therapy (6 months) with periodic urine cultures.

• Symptomatic re-infections with sexual activity:

  • Single-dose prophylactic therapy: 1 Single Strength (SS) Sulfamethoxazole/Trimethoprim tablet or Nitrofurantoin (Macrobid®) after intercourse.

  • Voiding after intercourse may also help prevent UTIs.

• Relapse after short-course therapy:

  • 14-day treatment.

Prostatitis

• Inflammation/infection of the prostate.

• Acute or chronic infection.

  • Acute: sudden onset of urinary & constitutional signs/symptoms.

• Diagnosis: Prostatic secretions & urine (bacteria & leukocytes).

• Organisms: Most common: Gram (-) enteric organisms.

  • Predominant organism: E. coli.

• Treatment:

  • Antimicrobials:

    • TMP/SMX (Bactrim®)

    • Fluoroquinolones: Ciprofloxacin, Levofloxacin

  • Duration:

    • Acute: 4 weeks

    • Chronic: 6-12 weeks

Epididymitis

• Bacterial (most common cause): Likely organism depends on the patient’s age.

  • Prepubertal: Coliform bacteria (E. coli) - Treatment: Sulfamethoxazole/Trimethoprim (Bactrim®).

  • Young adult to middle age: C. trachomatis, N. gonorrhoeae - Treatment: Ceftriaxone (Rocephin®) 500 mg IM x 1 dose & Doxycycline 100mg PO BID x 10 days (or Ceftriaxone 500mg IM x 1 plus Levofloxacin 500mg Qday x 10 days in MSM).

  • Older males: Coliform bacteria (E. coli) - Treatment: Sulfamethoxazole/Trimethoprim (Bactrim®) or Levofloxacin.

• Other causes:

  • Post-infectious (inflammatory reaction) - After systemic infection.

  • Chemical epididymitis - reflux of urine causes an inflammatory response.

Urethritis

• C. trachomatis, N. gonorrhoeae

• Treatment: Ceftriaxone & Azithromycin (or Doxycycline).

Urinary Analgesic

Phenazopyridine

• Rx: Pyridium® 100 mg & 200 mg tablets.

• Dosage: 200 mg PO TID with food.

• OTC: 95 mg (AZO-Gesic, AZO-Standard, & Uristat); 97.2 mg (UTI Relief).

• Mechanism of Action (MoA): acts directly on urinary tract mucosa to produce local analgesic effect.

• Use:

  • Symptomatic relief of pain, burning, urgency, frequency arising from irritation of the lower urinary tract (from instrumentation, irritation, or infection).

  • Useful with initiation of antimicrobial (symptomatic relief until antimicrobial controls infection).

• Adverse Effects:

  • Red-Orange discoloration of urine.

  • Abdominal cramping, Headache (HA).

  • Rare - hepatitis, acute renal failure, hemolytic anemia.

Other Treatments for UTI

• Estrogen cream

  • Postmenopausal women.

• Cranberry

  • Doesn’t help treat active UTI.

  • Might help prevent recurrent infections.

  • Prevents bacterial adhesion to the urethral wall.

UTI Summary

Fluoroquinolones: Interactions and Adverse Effects

Interactions

• Ingestion with antacids (Aluminum (Al) or Magnesium (Mg)).

• Dietary supplements with iron or zinc, Calcium (Ca) (supplements or food).

Adverse Effects

• Gastrointestinal (GI): Nausea/Vomiting/Diarrhea (N/V/D).

• Hypoglycemia.

• Phototoxicity.

• Connective tissue problems:

  • Avoid in pregnancy & lactation and in pediatrics (under 18 years of age) due to cartilage erosion.

  • Tendon rupture.

• Black Box warning:

  • Patients >60 years old, concomitant corticosteroid therapy, & patients with kidney, heart, or lung transplant.

• Central Nervous System (CNS) effects:

  • Convulsions, increased Intracranial Pressure (ICP), and toxic psychosis.

SMZ/TMP

Sulfonamides

Mechanism of Action (MoA)

• Inhibition of the synthesis of bacterial dihydrofolate acid (essential cofactor).

Antimicrobial Spectrum

• Bacteriostatic.

• Enterobacteria in the urinary tract.

Kinetics

• Liver metabolism, urinary excretion.

Drugs

• Sulfamethoxazole/Trimethoprim (Bactrim DS, Septra DS).

Adverse Effects

• Crystalluria.

• Hypersensitivity:

  • Rashes, angioedema, Stevens-Johnson Syndrome (SJS).

• Hemopoietic disturbances.

• Kernicterus:

  • Avoid in newborns & infants less than 2 months of age (displace bilirubin from binding sites on albumin → bilirubin in the Central Nervous System (CNS)).

  • Avoid in pregnant patients near term.

Nitrofurantoin (Macrobid®)

Mechanism of Action (MoA):

• Inhibits various enzymes in bacteria and damages DNA.

Adverse Effects (AE):

• Discoloration of urine, hemolytic anemia (Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency), Gastrointestinal (GI) upset, acute pneumonitis, neurological problems.

Contraindications:

• Anuria, oliguria, pregnancy ≥ 38 weeks.

Gentamycin

• MoA: diffuse through porin channels (oxygen dependent transport system) → bind to the 30 S ribosomal subunit → interrupting protein synthesis

• AE: nephrotoxicity, ototoxicity, and allergic reactions such as rash or anaphylaxis.

Azithromycin

• MoA: Irreversibly bind to the 50S bacterial ribosomal subunit→ inhibiting translocation step of protein synthesis

• AE: N/V/D, Cholostatic juandice