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Antibiotics: UTI's
Urinary tract infection, pyelonephritis,
31
Pharmacology
10/26/2010

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Term
Genitourinary anatomy
Definition
-Females greater chance of getting infection than males. Because...
-Longer urethra prevents bladder inoculation.
-Anatomic proximity from GI tract
-Antimicrobial prostate secretions
-Males must have abnormality to develop UTI. (Rare in men <50 y/o)
Term
Physiologic Defenses against UTI's
Definition
-Anatomy (normal)
-Mechanical voiding
-Urethral and vaginal colonization with fecal flora
-Urine defenses (low pH, high osmolality, high urea, uroepithelial glycoproteins)
-PMNs
Term
UTI Risk Factors
Definition
-Sexual intercourse
-Recent antibiotics
-Recent history of UTI
-Pregnancy
-Vesicoureteral reflux
-Obstruction (kidney stone, BPH, tumor, strictures)
-Mechanical instrumentation
-Anticholinergics (TCA's, diphenhydramine, dicyclomine, oxybutinin)
-Neurologic dysfunction
Term
Classification- based on where the infection is located
Definition
Upper tract infection:
-Kidneys: pyelonephritis

Lower tract infection:
-Bladder- cystitis
-Urethra- urethritis
-Prostate gland- prostatitis
Term
Classification- based on severity
Definition
Uncomplicated:
-Healthy, non-pregnant female

Complicated:
-Medical condition (diabetes, CKD)
-Structural abnormality
-Instrumentation
-Functional deficit (CVA, SCI, obstruction)
-Immunosuppression/hospital acquired
-Pregnancy
**Usually associated with MDR origanisms
Term
Common community aquired bacteria
Definition
Cystitis:
-E.Coli (most common)
-P. mirabilis, K. pneumoniae
-S. saphrophyticus

Pyelonephritis
-E. coli (almost always ~90%)
Term
Ascending UTI
Definition
Microbes ascend the urethra to the bladder
-Sexual intercourse
-Altered flora
-Impaired urine flow or incomplete voiding
Fimbriae adhere to uroepithelial cells
-Resist glycoproteins
-No PMN fibriae recognition
Term
Descending UTI
Definition
-Hematogenous spread to kidney from another site
-Spread from blood to kidney to bladder
-Rare
-Gram (+) organisms (usually S. aureus)
Term
Cystitis: Signs and symptoms
Definition
-Dysuria
-Urgency
-Pain
-Frequency/burning
-Suprapubic pain
-Cloudy, foul smelling urine +/- hematuria
Term
Pyelonephritis: signs and symptoms
Definition
-Flank pain
-N/V
-Abdominal pain
-Fever, chills
-Malaise
Term
Urinalysis
Definition
-Midstream urine clean catch
-Catheterization
-Suprapubic bladder aspiration (usually only done in neonates)
Term
Urinalyis Interpretation for UTI
Definition
WBC- pyuria
-non-specific
-Inflammation may/may not be due to infection
Leukocyte esterase
-Quantifies amount of neutrophil esterase enzyme released to determine degree of pyuria
Nitrite (positive or not, could be infection)
-Detects gm (-) reduction of dietary NO3
-Non-reducers: Gram (+), P. aeruginosa
Term
Urine culture
Definition
-Gold standard for dx
-
Term
Urine Culture
Definition
-Gold standard for diagnosis
-Males: symptoms + >/= 1,000 cfu/ml
-Females: symptoms + >/= 1,000 cfu/ml

Multiple organisms may represent contamination
Term
Treatment: when to initiate
Definition
Cystitis
-Positive local signs & symptoms
-Urine dipstick positive LE and or nitrite or urine culture >1,000 cfu/ml (if obtained)

Pyelonephritis
-Positive systemic signs & symptoms
-Urine culture >10,000 cfu/ml
Term
When to obtain urine cultures
Definition
1. Negative urine dipstick despite s/sx
2. Not responding to tx
3. Suspected pyelonephritis
4. Atypical s/sx
5. Relapse despite recent tx
6. Positive pregnancy screen
7. Confirm cure following pyelonephritis
Term
SMX/TMP
Definition
Use double strength BID
Uncomplicated: 3 days
Complicated: 10-14 days
Pyelonephritis: IV/po 10-14 days

Benefits: 100% renal elim, good PO absorption
Drawbacks: Pregnancy C (neural tube/kernicterus), ~30% E. coli resistance.

Hyperkalemia: increased risk if also on ACE/ARB
Crystalluria and bone marrow suppression (adverse events)

Monitor: hydration, SCr, K, and CBC
Term
Fluoroquinolones
Definition
Levofloxacin QD
Cipro BID
Uncomplicated: 3 days
Complicated: 10-14 days
Pyelonephritis: IV/po 10-14 days

Benefits: Bactericidal, good urine & prostate concentrations, pseudomonas coverage
Drawbacks: QTc prolongation, promote resistance, Ca++ decrease absorption, preg C, not for S. aureus UTIs, avoid in children
Term
Nitrofurantoin
Definition
Only for uncomplicated!: 100mg po BID x 7 days

Benefits: Bactericidal, adequate urine levels, good po absorption, pregnancy B (C in 3rd term)
Drawbacks: Not good for pyelonephritis,
Macrodantin QID dosing, contraindicated if <60ml/min CrCl, no proteus/pseudo coverage

Monitoring: pulmonary sx, LFTs, pain sx, educate about dark urine
Term
Beta lactams (oral)
Definition
Amoxicillin (uncomplicated only): 500 mg po TID x 7 days
Amox/Clav (complicated/pyelo): 500mg po BID x 14 days
Cephalexin (uncomplicated): 250-500mg po QID x 7 days
Cefpodoxime (complicated): 200mg po BID x 10 days

All are preg B
Term
Phenazopyridine
Definition
Urinary analgesic
-For dysuria due to UTI, trauma, or surgery
-Inappropriate for self-care
-False-negative leukocyte esterase test
-Place in tx: adjunct for max 2-3 days with concurrent AB tx
Term
Uncomplicated cystitis: treatment
Definition
3 day regimen (higher cure rates for uncomplicated females)
-Bactrim DS 1 po BID
-Cipro 250-500mg po BID
-Levaquin 250-500 po QD

7 day regimens:
-Nitrofurantoin (macrobid 100mg po BID or macrodantin 50-100mg po QID)
-Amoxicillin 500mg po TID or Amox/clav 500mg po BID
-Cephalexin 250-500mg po QID
Term
Complicated Cystitis: treatment
Definition
-Remove obstruction/correct abnormality
-Urine cultures (use to de-escalate tx)
-Broad spectrum AB therapy (see pyelonephritis)
-Tx for 10-14 days
Term
Pyelonephritis: IV treatment
Definition
Cipro 400mg q12h/Levo 500mg q24h
Gent/tobra 3-5mg/kg (IBW) q 24h x 1-3 doses +/- ampicillin/sulbactam
Ceftriaxone 1 gm q 24h or cefipime 1gm q6h
Piperacillin/tazobactam 3.375gm q6-8h
TMP/SMX 8-10mg/kg q12h
Term
Pyelonephritis: PO treatment
Definition
Only if there are mild symptoms

Cipro 500mg BID x 10-14 days
Cefpodoxime proxetil 200mg BID x 10 days
Levaquin 500mg daily x 10 days
Amox/clav 500mg TID x 14 days
TMP/SMX DS BID x 14 days
Term
Pyelonephritis: Guidelines for Tx
Definition
-Start empiric therapy after urine and blood cultures
-IV antibiotics, at least for first dose
-De-escalate tx based on sensitivities
-Consider po to complete 10-14 day course
-Reculture 1-2 weeks after tx completion
Term
Pyelonephritis: IV vs PO candidates
Definition
PO:
-Low-grade fever
-Normal or slightly elevated WBC count
-No N/V

IV:
-High fever, elevated WBC, sepsis
-N/V, dehydration
-Tract obstruction
-Bacteremia
-Uncomplicated cystitis progression
Term
Asymptomatic Bacteriuria
Definition
-2 consecutive voided urine specimens (women) or 1 sample (men) >100,000 cfu/ml without sx
-Common in elderly, institutionalized, indwelling catheter pts
-Positive urine culture alone not diagnostic for UTI

DO NOT TREAT unless pregnant or urology surgery
Term
UTI's in pregnancy
Definition
Physiologic changes in pregnancy:
-Dilation of renal pelvis and ureters
-Decreased ureteral peristalsis
-Reduced bladder tone
-Nutrient-rich urine

Result in urinary stasis and reduced defenses against reflux

If positive asymptomatic culture tx x 7 days (reculture w/in 7-14 days after tx completion + monthly until preg complete):
-Cephalexin, amoxicillin, fosfomycin, +/- nitrofurantoin (not 3rd trimest)

AVOID: FQ's, Tetracyclines, TMP/SMX

Tx failure: alternative AB x 14 days
Term
Recurrent UTI prevention: Prophylaxis
Definition
Low dose AB's
-Daily or QOD @ HS
-Post-coital prophylaxis x 1 dose
-Patient-initiate tx x 3 days

SMX/TMP or nitrofurantoin- 1st line

When to initiate?:
>/= 2 symptomatic infections in 6 months
>/= 3 symptomatic infections in 12 months
Term
Bacterial prostatitis
Definition
Infection of prostate gland and surrounding tissue

If occurs in men <35 y/o, STD is common cause: gonorrhea or chlamydia

Acute s/sx: high fever/chills, dysuria/myalgias, pelvic/perineal pain (treat 4 weeks)
Chronic: nonspecific perineal pain >3 months (treat 6-12 weeks)