Document 6429995

Urinary Tract Infections
Urinary Tract Infections
Keri A. Mattes, Pharm.D., BCPS
September 15, 2003
7 million episodes of acute cystitis and
250,000 episodes of pyelonephritis
annually in the U.S.
Epidemiology
Women
z
z
1 in 3 infected before age 24
50% have at least one during their lifetime
Epidemiology
7 million office visits
1 million ER visits
100,000 hospitalization
in 1997
Men
z
Incidence is very low prior to age 50
Epidemiology
Cathether-associated UTI
Most common nosocomial infection
z >1 million cases in hospitals and NHs
z
Implications
Financial
z
z
Community acquired UTI = $1.6 billion
Nosocomial UTI = >$400 million
Elderly
z
z
2nd most common form of infection
25% of all infections
1
Implications
Assess the Patient
Medical
Classify by:
Bacteremia
z Symptoms
z Pregnancy
Location
Complications
z Organisms
z Pathophysiology
z
z
z
z
z
Pyelonephritis, premature delivery, fetal
complications and mortality, PIH
z
Pediatrics
z
Host defense mechanisms, virulence factors
Risk Factors
z Clinical Presentation
z
Impaired renal function, renal scarring, ESRD
*
*
Classification of UTIs
Complicating Factors
Lower Tract
z
z
z
z
Male Sex
Elderly
Indwelling urinary
catheter or recent
instrumentation
Obstruction/Stone
Prostatic Hypertrophy
Pregnancy
Urethritis
Cystitis
Prostatitis
Epididymitis
Upper Tract
z
z
Pyelonephritis
Intrarenal/perinephric
abscess
Etiology Uncomplicated
Infections
E. coli
80%
Staph. Saprophyticus
10-15%
Klebsiella
less common
pneumoniae,Proteus sp.,
Enterobacter and Enterococcus sp.
*
Diabetes
Immunosuppression
Neurologic Deficit
Childhood UTI
Recent antibiotic use
Symptoms for > 7 days
Hospital-acquired
infection
Presents at an urban ER
Etiology – Complicated
Infections
E. coli
Enterococcus fecalis
Proteus sp.
K. pneumoniae
Serratia marcescens
Enterobacter sp.
P. aeruginosa
Staph aureus
Enterococci
Candida sp.
<50%
2
Etiology - Pediatrics
Etiology - Elderly
E. coli
Proteus sp.
Klebsiella sp.
Serratia marcescens
E. coli
Polymicrobial
Etiology – Spinal Cord
Injury or Catheterized
Etiology - Diabetes
Klebsiella sp.
Enterococcus
E. coli
Candida sp.
E. coli
Pseudomonas aeruginosa
Proteus mirabilis
Staph. aureus
Enterococci
Candida sp.
*
Etiology-HIV/AIDS
Enterococcus sp.
Pathophysiology
Ascending
Hematogenous
Lymphatic
3
*
*
Defense Mechanisms
Low pH
Stimulation of bladder
emptying/diuresis
Extremes in osmolality
High urea
concentration
Antiadherence
z
z
High Organic Acid
Conc.
Glycosaminoglycan
layer
Tamm-Horsfall protein
Immunoglobulins
z
Virulence
Ability to adhere to epithelial cells
z
Bacterial fimbrae
Hemolysin
Bacterial Glycocalyx
Urease Production
IgG and IgA
Prostatic secretions
*
Risk Factors
Female
Extremes of age
Obstruction
Diabetes
Immunosuppression
Pregnancy
History of UTI
Instrumentation
Neurologic
dysfunction
Renal disease
Sexual intercourse
Diaphragm or
spermicide use
Antimicrobial use
Short Urethra
Proximity of urethra
to perirectal area
Use of spermicides
and diaphragms
Lack of prostatic
fluid
Clinical Presentation
Lower Tract
Why women > men?
Upper Tract
Clinical Presentation
Elderly
z
Dysuria
z
Lower tract symptoms
z
Typical symptoms may be absent
z
Urgency
z
Frequency
Flank pain/CVA
tenderness
z
z
Altered mental status, change in eating
habits, gi symptoms
z
Nocturia
z
Suprapubic heaviness
z
+/- gross hematuria
z
Abdominal pain
z
Fever
N/V
Malaise
Increased WBC
z
z
z
4
Recurrent UTI
Re-infection vs. Relapse
Re-infection
UTI that occurs more than 2 weeks after
treatment of the first UTI
z
Risk Factors:
Sexual intercourse
Diaphragm/spermicide use
z History of recurrent UTIs
z First UTI at < 15 yo
z Mother with a history of UTIs
z Reduced levels of estrogen
z
z
Re-infection
No proven association with:
Pre and post-coital voiding patterns
z Frequency of urination
z Delayed voiding habits
z Wiping patterns
z Douching
z Use of hot tubs
z Frequent use of pantyhose or tights
z BMI
z
Relapsing UTI
Within 2 weeks after treatment
Resistance
Nonadherence
Inappropriate choice of antibiotic
Complicating factors
Symptomatic
Abacteriuria
Urethritis
z
C. trachomatis, N. gonorrhoeae, herpes
simplex virus
z
Clinical Presentation:
z
Gradual onset, mild symptoms, vaginal
discharge or bleeding, lower abdominal pain,
new sexual partner, cervicitis, vulvovaginal
herpetic lesions on exam
Symptomatic
Abacteriuria
Vaginitis
z
Candida sp., Trichomonas vaginalis
z
Clinical Presentation
z
Vaginal discharge or odor, pruritus, external
dysuria, no increased frequency or urgency,
vulvovaginitis on exam
5
*
Diagnosis
Clinical presentation and:
z
z
history alone, if no risk factors
dipstick urinalysis
Urinalysis
pH
RBC
Leukocyte
Esterase
WBC
Casts
Nitrite
Other: glucose,
ketones, epithelial
cells, color/
appearance
Protein
Urinalysis
pH
leuk. est.
Nitrite
Protein
RBC
WBC
Casts
5.5
trace
negative
30 mg
negative
2/hpf
negative
Urinalysis
pH
leuk. est.
Nitrite
Protein
RBC
WBC
Casts
Urinalysis
pH
leuk. est.
Nitrite
Protein
RBC
WBC
Casts
6.5
large
positive
>300 mg
2/hpf
14/hpf
negative
7.0
large
positive
> 300 mg
5/hpf
18/hpf
positive
Urine Culture
Acute uncomplicated cystitis in women
z
No culture needed
Symptomatic patients
z
> 105 organisms/ml
Asymptomatic women
z
> 105 organisms/ml
Men
z
> 103 organisms/ml
6
Resistance
Resistance
Risk Factors
z
z
z
z
z
z
z
z
Recent or current antibiotic use
Age
Diabetes
Recent hospitalization
History of UTI
Cancer
Chronic neurologic or urologic disorder
Long term care facility
Resistance
Goals of Therapy
Very low for fluoroquinolones and
nitrofurantoin
Prevent or treat systemic consequences
of infection
Increasing for TMP-SMX
Eradicate the invading organism
>28% for beta-lactams
Prevent recurrence of infection
Appropriate Therapy
Well tolerated
Safe
Well absorbed
Achieve high urinary concentrations
Cover suspected pathogen
Acute Uncomplicated
Cystitis
Single dose
3 day
7
Acute Uncomplicated
Cystitis
Acute Uncomplicated
Cystitis
Single dose therapy
z
3-day therapy
65-100% cure rates
Superior to single-dose
Equal efficacy to 7-day therapy
z Increase adherence, decrease cost and
ADRs compared to 7-day
z
TMP/SMX DS #2
z Gatifloxacin 400mg
z Fosfomycin 3g
z
z
*
3-day Therapy
TMP/SMX DS po bid
TMP 200mg po bid
Acute Uncomplicated
Cystitis
Short-course therapy inappropriate for:
Complicated UTIs
Patients with comorbidities
z History of infections caused by
resistant bacteria
z
z
If E. coli resistance > 10-20%
z
Fluoroquinolones
Case #1
CC: “burning when I pee”
HPI: 27 yo WF comes into
clinic stating that the pain
started last night (12 hr
ago) and has gotten worse
today. Also has increased
frequency.
PMH: pregnant, exerciseinduced asthma
FH: non-contributory
Case #1
SH: - EtOH, - Tob,
works as a fashion
designer
ALL: PCN
Meds: Albuterol
inhaler prn
PE: negative
Need a UA??
8
Trimethoprim/
Sulfamethoxazole
Case #1
U/A: Lg leuk. est.,
nitrite +, 20
wbc/hpf,protein -,
3+ bacteria
1 DS po BID x 3 days
z
The “standard therapy” for acute
uncomplicated cystitis
7-10 day therapy for complicated cystitis
Safe in 1st and 2nd trimester of
pregnancy
Fluoroquinolones
Uncomplicated and Complicated
Cystitis
z
3-10 day therapy
FQ-Drug Interactions
Al, Mg, Ca, Fe
Warfarin
Theophylline, cyclosporine
1st line if TMP/SMX resistance
is >10-20%
Contraindicated in pregnancy
Trimethoprim
Uncomplicated and Complicated
Cystitis
7 day therapy with TMP equal efficacy
to 7 days of TMP/SMX
Nitrofurantoin
Uncomplicated and Complicated Cystitis
Not recommended for 3 day therapy
Useful if TMP/SMX resistant organism
Safe in pregnancy
Avoid use if Cr Cl < 50 ml/min
9
Beta-lactams
Uncomplicated and Complicated Cystitis
Urinary Analgesia
Phenazopyridine
Not recommended for short-course therapy
z
100-200mg po TID x 2-3 days
Less effective in eradication of bacteriuria
and prevention of recurrence
z
Discolors urine
z
Not useful if Cr Cl < 50 ml/min
Safe in pregnancy
Treatment – Case #1
Complicated Cystitis
Treatment for 7-10 days
Monitor
Resolution of symptoms in 24-48 hours
F/U urine culture for identification and
sensitivity of organism
Repeat UA and culture only if symptoms
not resolving
Adverse effects of individual drug
therapy
Acute Pyelonephritis
Upper UTI
z
Flank pain, CVA tenderness, abdominal
pain, fever, N/V and malaise
Hospitalization/IV antibiotics
indicated:
N/V
Dehydration
z Pregnancy
z
z
10
Uncomplicated vs.
Complicated
FQ x 14 days
z
*
IV Therapy
FQ
FQ x 14 days
Cipro x 7 days
AG +/- ampicillin
TMP/SMX DS x 14
days
z
3rd
z
z
or 4th generation cephalosporin
z
Ampicillin or
Amox/Clav
Gent/Tobra peak 6-10, trough < 2 µg/mL
Cefotaxime, Ceftriaxone, Ceftazidime, Cefepime
ß-lactam/ ß-lactamase inhibitor +/- AG
x 14 days
Gram + cocci
z
Gent/Tobra peak 3-6, trough < 2 µg/mL
IV Æ PO
Monitor
Afebrile x 24 hours
Symptoms should resolve in 48-72
hours
F/U urine culture in 2 weeks to ensure
eradication
Renal function for antibiotic dosing and
renal impairment
Adverse effects of drug therapy
Expect symptoms to resolve after 48-72
hours of therapy
*
Prostatitis
Acute
vs.
Chronic
Sudden onset
Relapsing UTI
Inflammation of the
prostate gland
Fever
Difficulty urinating
Rare if < 30 y.o.
Tenderness
Lower back pain
Urinary symptoms
Suprapubic
tenderness
11
Risk Factors
Sexual intercourse
Indwelling catheters
Urethral instrumentation
Transurethral prostatectomy
Prostatitis Pathogens
E. coli
K. pneumoniae
P. mirabilis
P. aeuriginosa
Serratia marcescens
75%
Altered prostate secretory function
BPH
Case #2
CC: fever, chills and
frequent urination
HPI: 57 yo white male with
onset of symptoms 6
hours ago, but increasing
in severity.
PMH: Multiple UTIs,
hyperlipidemia, BPH
Case #2
SH: EtOH 4 beer/day
and Tob 2ppd/60pyh
ALL: NKDA
Meds: Bactrim SS
bid, Lipitor 10 QHS,
Hytrin 5 QHs
FH: non-contributory
Case #2
PE: Tm 1028, very
tender prostate
upon rectal exam
U/A: pH 8, Lg leuk
est, 20 wbc/hpf,
nitrite+, 1-2
rbc/hpf, trace
protein, no casts
Prostatitis Therapy
Acute x 4 weeks
Chronic x 4-6 weeks
FQ
z TMP/SMX
z
12
Asymptomatic
Bacteriuria
Treatment – Case #2
Cipro 500 mg po
BID
z
Urine culture > 105 of the same
organism x 2
x 4 weeks
Occurs in 4-10% of pregnant women
*
ASB
Treatment of
Asymptomatic Bacteriuria
Risk Factors
Pregnancy
z Elderly
z Female patients with diabetes
z History of UTI
z Lower education
z
Treat
Do not treat
Children
Elderly
Pregnancy
(Catheterized)
Diabetes
UTIs in Catherized and
Spinal Cord Injury Patients
Most common nosocomial infection
Acquisition rate is 5% per day
>30 days, 78-95% incidence of
bacteriuria
40% of SCI patients die of renal-related
problems
Treatment of ASB
(Catheter & SCI)
Remove catheter and monitor for
symptoms
13
Symptomatic UTICatheterized/SCI
Culture
Remove/Change catheter
Treat as complicated
z
*
7-14 days
*
UTI Prevention
or eliminate use of spermicides
and/or diaphragms
Cranberry Juice
Estrogen in postmenopausal women
Antimicrobial prophylaxis IF:
> 2 symptomatic UTIs over a 6 month
period
z > 3 over 12 months
z
Antimicrobial
Prophylaxis
Continuous
Antimicrobial
Prophylaxis
Post-coital
TMP/SMX SS
TMP 100mg
z Nitrofurantoin 50-100mg
z Cephalexin 250mg
z Norfloxacin 200-400mg
z Ciprofloxacin 250mg
Nitrofurantoin 50mg po QD
z Trimethoprim 100mg po QD
z TMP/SMX SS tab po QD or 3x/week
z Norfloxacin 200 mg po 3x/week
z
z
z
Self-treatment
Funguria
Candida albicans
z
40-65%
C. tropicalis, C. krusei, C. glabrata
Funguria
Lower tract
z
Ascending route
Upper tract
z
Hematogenous route
14
Funguria - Risk Factors
Reversible
z
z
z
z
Antibacterial therapy
Indwelling urinary catheter
Anatomical abnormalities
Urinary tract manipulation/instrumentation
Funguria Treatment
Spontaneous Resolution
z
23%
Non-pharmacological
z
Reverse any reversible risk factors
Irreversible
z
z
z
Female
Diabetes
Immunosuppressive therapy
Funguria - Treatment
Fluconazole
z
200 mg x 1, then 100 mg/day x 4 days
Fluconazole & Ampho B
Advantages
z
High levels in urine
z
Good bioavailability
z
Sustained fungicidal
effect
z
Ease of
administration
Amphotericin B
Continuous low concentration
z Intermittent high concentration
z
Disadvantages
z
Doesn’t clear
funguria as rapidly
z
Optimum dosage
and duration
unknown
Urinary Tract
Infections
Keri A. Mattes, Pharm.D., BCPS
September 15, 2003
15