UTI 101: Antimicrobial agents,
duration and prophylaxis
April 30, 2012
Jennifer J. Schimmel, MD
Baystate Medical Center
Division of Infectious Diseases and
Antimicrobial Stewardship
Objectives
• Describe the agents used for treating bacterial
urinary tract infections (UTI’s) and understand
how to choose the most appropriate agent
• Understand the appropriate duration of
therapy and monitoring
• Understand the options for prophylaxis of
recurrent UTI
Background
• UTI is one of the most common infections in the
elderly in the community and in long-term care
• Two problems: overdiagnosis and overtreatment
• Subsequent issues:
– C. difficile
– Antibiotic resistance
• What’s important?
– Proper diagnosis
– Appropriate antibiotic choice and duration
Defining the Problems
• Lower UTI: infection in bladder and/or urethra
• Uncomplicated UTI: lower UTI AND
– Not pregnant
– No urinary tract abnormalities
– No indwelling urinary device
• Complicated UTI:
–
–
–
–
Upper UTI (systemic symptoms, extension beyond urethra/bladder)
Functional or structural urinary tract abnormality
UTI in men
Urinary catheter (CA-UTI)
– Older female patients
• Many have functional or structural abnormalities
Microbiology in Nursing Homes
• New Haven, CT
• 5 Nursing Homes May 2005-2007
• 551 patients, presumed UTI
Das R et al. ICHE 2009;30(11):1116-1119.
Case 1
• 75 year old woman s/p recent vertebral
fracture, in NH for past 2 weeks, no prior UTI’s
• Now several days of urinary frequency,
urgency, burning
• No fevers or back pain
• U/a with significant pyuria
• Started empirically on ciprofloxacin
What to use empirically?
• Take into account most likely uropathogens
• Patient Factors
–
–
–
–
Other medications/interactions
Allergies
Other past infections
Other medical problems (renal insufficiency, C.diff,
etc)
• Threshold for failure
• Local epidemiology
• Cost
Antibiogram
• Helps to determine best choices for empiric
therapy
Case 1: Culture Data
What can you do now?
Collect date: 04/15/12 08:35
Result Status: Auth (Verified)
Result Date: 04/17/12 09:33
SPECIMEN DESCRIPTION : URINE CLEAN CATCH/MIDSTREAM
SPECIAL REQUESTS : NONE
CULTURE : >100,000 COL/ML ESCHERICHIA COLI
TEST PERFORMED AT BAYSTATE MEDICAL CENTER, SPRINGFIELD, MA. 01199
REPORT STATUS : FINAL 04/17/2012
ORGANISM
>100,000 COL/ML ESCHERICHIA COLI
METHOD
MIN. INHIB. CONC. (MCG/ML)
AMPICILLIN
RESISTANT
AMPICILLIN/SULBACTAM INTERMEDIATE
AMOXICILLIN/CLAVULAN SUSCEPTIBLE
CEFAZOLIN
SUSCEPTIBLE
CEFEPIME
SUSCEPTIBLE
CEFTRIAXONE
SUSCEPTIBLE
CIPROFLOXACIN
SUSCEPTIBLE
ERTAPENEM
SUSCEPTIBLE
GENTAMICIN
SUSCEPTIBLE
LEVOFLOXACIN
SUSCEPTIBLE
MEROPENEM
SUSCEPTIBLE
NITROFURANTOIN
SUSCEPTIBLE
PIPERACILLIN/TAZOBAC SUSCEPTIBLE
TRIMETH/SULFAMETHOX SUSCEPTIBLE
TETRACYCLINE
SUSCEPTIBLE
Seeking the perfect antibiotic…
• Needs to get into urinary tract
– And sometimes the prostate
•
•
•
•
•
•
•
Treat specific organism
Narrowest spectrum possible
Minimize adverse effects
Avoid drug interactions
No allergy
Compliance
Cost
• Oral option?
Case 2
• 75 year old woman with well-controlled Crohn’s
disease on mesalamine, admitted with syncopal event
• Found to have conduction abnormality
• Allergy to penicillin (unknown)
• Has pacemaker placed (perioperative Clindamycin)
• 2 days after procedure still has unexplained
leukocytosis with WBC 13
• no obvious source of infection, no urinary symptoms,
no diarrhea, CXR unremarkable, u/a with 1 wbc
Case 2
• Urine culture pending at the time of discharge to
rehab
• What would be the next best step?
A) Discharge on 5 days of Levofloxacin for possible UTI
B) Follow off antibiotics
C) Keep her in the hospital and repeat u/a tomorrow
D) Treat with Ceftriaxone 1g IV and additional antibiotics
base on culture data
E) Treat with Tobramycin 5mg/kg and additional
antibiotics based on culture data
C. diff-o-genicity
• High risk
– Carbapenems
– 2nd – 4th generation
cephalosporins
– Fluoroquinolones
– Clindamycin
• Medium risk
–
–
–
–
Penicillins
1st generation cephalosporins
Macrolides
Aztreonam
Mullane et al. Clin Infect Dis. 2011;53:440-447.
• Low risk
–
–
–
–
–
–
–
–
–
–
Aminoglycosides
Vancomycin
Daptomycin
Nitrofurantoin
Linezolid
Trimethoprim/
sulfamethoxazole
Tetracyclines
Rifampin
Colistin
Fosfomycin
Recommendations from the
Guidelines
Uncomplicated UTI: Lower Tract
Gupta K et al. Clinical Infectious Diseases 2011;52(5):e103-120.
Nitrofurantoin (Macrobid,
Macrodantin)
• Minimal “collateral”
damage
• DRUG INTERACTIONS
– Minimal
– Concomitant administration
of a magnesium trisilicate
antacid may decrease the
absorption of nitrofurantoin
– Nitrofurantoin may reduce
the effect of quinolone
antibiotics
– Fluconazole: increased risk of
pulmonary and hepatic
toxicity
• Avoid if creatinine
clearance less than 60
– Due to potentiation of
adverse effects
• Common side effects:
nausea, headache
• Other serious adverse
effects:
–
–
–
–
–
Peripheral neuropathy
Pulmonary hypersensitivity
Hepatoxicity
Decreased renal function
Hemolytic anemia
Fosfomycin
• Issues:
–
–
–
–
–
–
–
Minimal resistance
Minimal collateral damage
High urinary levels
Prolonged bactericidal effect
Minimal drug interactions
Not always available
Susceptibility data not
routinely available
– Role for treatment of
resistant organisms such as
ESBL’s, VRE, MRSA
– Maybe less effective than
other short-course regimens
Trimethoprim/Sulfamethoxazole
TMP/SMX (Bactrim)
• DRUG INTERACTIONS
–
–
–
–
Warfarin
Methotrexate
Fluconazole (incr QT)
TCA, antipsychotics,
antiarrhythmics
– Antihyperglycemics
• Common side effects:
nausea, vomiting, rash
• Other serious adverse
effects:
–
–
–
–
–
Bone marrow suppression
Hepatic necrosis
Severe rash
Hyperkalemia
Hypoglycemia (esp with renal
and liver disease)
• Increased creatinine…may
be falsely elevated
Quinolones: Ciprofloxacin and
Levofloxacin
• Highly efficacious in a 3day regimen
• Numerous issues with
collateral damage:
C.difficile and resistance
• Save for other uses
• Black Box Warning:
tendonitis/tendon
rupture esp. over age 60,
steroids, transplant
• Interactions:
– calcium, aluminum, magnesium,
iron, and zinc (antacids,
nutritional supplements,
multivitamin and mineral
supplements), sucralfate
– Warfarin
– Antihyperglycemics
• Other issues:
– QT prolongation esp. in elderly
– Decreased seizure threshold
•
Upper Tract Infection: Acute
Pyelonephritis
Not requiring hospitalization (and resistance less than 10%):
– Ciprofloxacin 500mg PO BID for 7 days
– Ciprofloxacin 1000mg ER for 7 days
– Levofloxacin 750mg for 5 days
– Bactrim DS BID for 14 days (if pathogen susceptible)
– Alternative initial IV antibiotic: Ceftriaxone 1g IV or Aminoglycoside
– Alternative: Oral b-lactam (initial IV dose Ceftriaxone) and 10-14 days
• Hospitalized:
– IV regimen:
• Fluoroquinolone
• Aminoglycoside +/- ampicillin
• 2nd or 3rd generation cephalosporin +/- aminoglycoside
• Extended spectrum penicillin +/- aminoglycoside
• Carbapenem
Gupta K et al. Clinical Infectious Diseases 2011;52(5):e103-120.
Catheter-Associated UTI (CA-UTI)
• Most common health care-associated
infection worldwide
• 40% of hospital-acquired infections
• 5-10% of LTCF residents with long-term
indwelling catheters
– Almost all have bacteriuria
– Single organism in short-term catheter
– Multiple organisms in long-term catheterization
Hooton TM et al. Clinical Infectious Diseases 2010;50:625-663.
CA-UTI
• E.coli (30%), Klebsiella species, Serratia
species, Citrobacter species, Enterobacter
species, Pseudomonas aeruginosa, coagulasenegative staphylococci, Enterococcus species
• Long-term catheters: the organisms above
and: Proteus mirabilis, Morganella morganii,
Providencia stuartii
CA-UTI
• Duration:
– Prompt resolution of symptoms: 7 days
– Delayed response: 10-14 days
– Not severely ill: 5 day Levofloxacin may be considered
– Women aged 65 or under with CA-UTI and no upper tract symptoms,
with removal of catheter: consider 3 days of therapy
• Other issues
– De-escalation/narrowing of therapy as soon as possible
– If catheter in place for >2 weeks and is still needed, catheter should be
replaced
• More rapid resolution of symptoms
• Decrease risk of subsequent CA-bacteriuria and CA-UTI
Hooton TM et al. Clinical Infectious Diseases 2010;50:625-663.
Case 3
• 68 yo woman with poorly-controlled diabetes,
dysuria, fever and chills
• Prior history of UTI’s with resistant Klebsiella
• No allergies
• WBC 18K
• Cr 2.6
• U/a with >182 wbc, 2 rbc, 1 sq epith cell
Limited Therapeutic Options
URINE CULTURE Final
Organism 1
KLEBSIELLA PNEUMO SSP PNEUMO.
COLONY COUNT
>100,000 CFU/ml
RESULT COMMENT:
** DRUG RESISTANT
ORGANISM **
Drug Resistant Organism
KLEBSIELLA PNEUMO. SSP PNEUMO.
MULTIPLE DRUG RESISTANCE
TRIMETHOPRIM/SULFAMETHOXAZOLE R >=320
AMPICILLIN
R >=32
AMPICILLIN/SULBACTAM
R >=32
CEFAZOLIN
R >=64
CEFOXITIN
R >=64
CEFTAZIDIME
R >=64
CEFTRIAXONE
R >=64
CEFEPIME
R >=64
CIPROFLOXACIN
R >=4
GENTAMICIN
R >=16
LEVOFLOXACIN
R >=8
IMIPENEM
R >=16
NITROFURANTOIN
R >=512
TOBRAMYCIN
R >=16
AMIKACIN
R >=64
PIPERACILLIN/TAZOBACTAM
R >=128
• What are the antibiotic
options in this case?
a)
b)
c)
d)
e)
None
Colistin
Gatifloxacin
Ertapenem
Other ideas?
New FDA Antibiotic Approvals
Boucher HW et al. Clinical Infect
Diseases 2009;48:1-12.
Increasing Resistant Organisms
Answers
• Colistin
• Tigecycline
• Fosfomycin
Case 3, Part 2
• Patient is treated with colistin, has resolution
of her symptoms, leukocytosis and eventually
improved renal function.
• Which of the following should be done?
A) Repeat u/a 7 days after therapy completed
B) Repeat urine culture 7 days after therapy
completed
C) A and B
D) Repeat u/a and culture are not indicated
Test of Cure
• Not routinely recommended
Case 4
• 70 year old woman with 4 E.coli UTI’s in the past
6 months, urologist notes a mild cystocele and
atrophic vaginal mucosa on exam
• What do you recommended?
A) Nothing
B) Bactrim DS BID indefinitely
C) Cranberry juice 8 oz daily
D) Topical estrogen
D) Cipro 500mg weekly
Recurrent UTI: Risk Factors
• Post-menopausal:
– estrogen deficiency
– urogenital surgery
– incontinence, cystocele, post-void residuals
• Men:
– Prostatic disease
• Both Men and Women:
– Obstruction: stones, tumor
• Complicated UTI:
– MDRO, obstruction, stasis, foley catheter, stent, diabetes, pregnancy,
renal failure, transplant, immunosuppression
Franco AV. Best Pract & Res Clin Obstet & Gynec 2005;19(6):861-73.
What else other than antibiotics?
• Fluids to promote a dilute urine flow
• Topical estrogen
– In some postmenopausal women it can normalize the
vaginal flora and reduce recurrent UTI
• Methenamine
• Adhesion blockers (D-mannose)
– Not evaluated in clinical trials
• Drinking cranberry juice or cranberry tablets
– Clinical Data Cochrane Review 2008
– Recent studies
– Pilot Study in LTC
Mayo Clinic Proceedings 2012 Feb;87(2):143-50
Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial.
Stapleton AE, Dziura J, Hooton TM, Cox ME, Yarova-Yarovaya Y, Chen S, Gupta K.
Source
Department of Medicine, University of Washington, Seattle, USA.
Abstract
OBJECTIVE:
To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month
period in women ingesting cranberry vs placebo juice daily.
PATIENTS AND METHODS:
Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1
of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome.
Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.
RESULTS:
A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of
UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the
placebo group was 0.68 (95% confidence interval, 0.33-1.39; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the
intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was
91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group
and 12.5% in the placebo group (P=.07).
CONCLUSION:
Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies
and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains
supports the biological plausibility of cranberry activity.
Juthani-Mehta M et al. Journal of the American Geriatric Socety 2010;58(10):2028-2030.
What about for CA-UTI?
• Reduce indwelling catheter use
• Remove catheters the as soon as they are no
longer clinically necessary
• Catheters
– Care
• Insertion with aseptic technique/sterile equipment
• Closed drainage systems, with drainage bag and tube always
below bladder level
– Antimicrobial coating
• May delay onset of CA-bacteriuria in short-term
Hooton TM et al. Clinical Infectious Diseases 2010;50:625-663.
What about for CA-UTI?
• Methenamine not recommended in long-term catheterization
– Data unconvincing that it is effective
– May be effective with intermittent catheterization and short-term
catheterization (studied in specific population)
• Methenamine hippurate 1 g BID
• Methenamine mandelate 1g 4 times daily
– And it may help to acidify urine when using these agents (Vit C?)
• Cranberry
– 3/4 double-blind placebo controlled trials: no effect
– Studies are poor, mostly negative
• Antimicrobial prophylaxis can reduce CA-ASB, but not CA-UTI
– Not recommended because of cost, potential for adverse effects and
development of antimicrobial resistance
Hooton TM et al. Clinical Infectious Diseases 2010;50:625-663.
In Summary
• Decide if treatment is necessary
• Appropriate antibiotic and duration
– Choice based on patient (allergies/comorbidities/prior
history), epidemiologic factors, organism
– Minimize adverse effects, minimize development of
resistance, avoid C.difficile
• Narrowest spectrum possible
• If empiric therapy is more broad than needed, narrow after culture
data
• Prophylaxis
– Several options that do not affect antimicrobial resistance
– Avoid antimicrobial agents if possible
– If such an agent is chosen, would re-evaluate after several
months
Questions?
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References
Barbosa-Cesnik C et al. Cranberry Juice Fails to Prevent Recurrent Urinary Tract Infection: Results from a
Randomized Placebo-Controlled Trial. Clinical Infectious Diseases 2011;52(1);23-30.
Beerepoot MAJ et al. Cranberries vs Antibiotics to Prevent Urinary Tract Infections. Archives of Internal
Medicine 2011;171(14):1270-78.
Beveridge LA et al. Optimal Management of Urinary Tract Infections in Older People. Clinical
Interventions in Aging 2011;6:173-180.
Boucher HW et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of
AmericaClinical Infect Diseases 2009;48:1-12.
Das R et al. Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing
Home Residents. ICHE 2009;30(11):1116-1119.
Franco AV. Recurrent Urinary Tract Infections. Best Pract & Res Clin Obstet & Gynec 2005;19(6):861-73
Gupta K et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis
and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the
European Society of Microbiology and Infectious Diseases. Clinical Infectious Diseases 2011;52(5):e103120.
Hooton, TM. Uncomplicated Urinary Tract Infection. NEJM 2012;366:1028-37.
Hooton TM et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in
Adults: 2009 Internation Clinical Practice Guidelines from the Infectious Diseases Society of America.
Clinical Infectious Diseases 2010;50:625-663.
Jepson RG et al. Cranberries for preventing urinary tract infections. Cochrane Review 2008.
Juthani-Mehta M et al. Feasibility of Cranberry Capsule Administration and Clean-Catch Urine Collection
in Long-Term Care Residents. Journal of the American Geriatric Socety 2010;58(10):2028-2030.
Mcmurdo MET et al. Does Ingestion of Cranberry Juice Reduce Urinary Tract Infections in Older People in
Hospital? A Double-Blind Placebo-Controlled Trial. Age and Aging 2005;34:256-261.
Mullane et al. Clin Infect Dis. 2011;53:440-447.
Nicolle LE et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of
Asymptomatic Bacteriuria in Adults. Clinical Infectious Diseases 2005;40:643-54.
Stapleton AE et al. Recurrent Urinary Tract Infection and Urinary Escherichia coli in Women Ingesting
Cranberry Juice Daily: A Randomized Controlled Trial. Mayo Clinic Proceedings 2012;87(2):143-50.