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1. Urinary Tract Infection, Complicated (UTI)
Michael Melia, M.D., James DeMaio, M.D.
PATHOGENS
Among the most common, resistant strains frequently encountered:
Enterobacteriaceae
Pseudomonas aeruginosa
Acinetobacterspp.
Less common:
MSSA or MRSA
Most due to invasion of urinary tract (secondary to catheters, stents)
Consider presentations of staphylococcal bacteremia with findings of S. aureus in urine.
Enterococcus spp. (including VRE)
Candida spp.
Fastidious organisms possible.
Infections may be polymicrobial, especially if chronic urinary catheter or stents are present.
CLINICAL
Complicated UTI (cUTI) lacks a consensus definition.
FDA definition: syndrome of infection in the presence of a urinary catheter or an anatomic or functional abnormality
Recurrent infection, whether reinfection or relapse, is common among patients with cUTI.
Risk factors for complicated UTIs:
Structural abnormalities: obstruction, foreign body (e.g., catheter, ureteral stent)
Functional abnormalities: "neurogenic" bladder
Metabolic or hormonal: poorly-controlled diabetes, pregnancy
Immune defect: renal transplant, neutropenia, advanced HIV infection
Symptoms are highly variable.
Lower tract infection: classically presents with dysuria, urgency, frequency, suprapubic pain, new or increased
incontinence, and lack of vaginal discharge
Upper tract infection: frequently associated with flank pain, fever and chills.
Presentation often modified by host factors:
Catheterized patients may only have fever and non-specific symptoms (e.g., malaise).
Recently quadriplegic patients may have increased spasticity or autonomic dysreflexia.
DIAGNOSIS
Urinalysis: leukocyte esterase (+), nitrite (+), urine with >10 WBC/hpf
Pyuria is a necessary but not sufficient diagnostic criterion.
Microbiology: urine culture and sensitivity essential to optimize treatment. Gram stain of spun urine may be useful in
selecting empiric antibiotics.
Catheterized ("straight cath") sample: often helpful to help distinguish pathogens from contaminants on "clean catch"
samples.
Indwelling catheters may be colonized with biofilm; remove and replace if feasible, with culture from newly placed
catheter.
If indwelling catheter or ureteral stent, ask laboratory to identify all species since multiple isolates or "skin flora" may
be genuine pathogens.
If patient is severely ill or not improving with therapy as anticipated, then image (renal ultrasound or abd/pelvic CT) to
exclude obstruction and/or abscess.
If cUTI suspected but underlying abnormality unknown, further evaluation (imaging and/or urology assessment)
warranted.
TREATMENT

2. Antimicrobials
Given heterogeneity of cUTI, recommendations for empiric therapy are challenging; must consider individual patient
context
Empiric therapy must be broad-spectrum with definitive therapy based on culture and sensitivity.
If patient mild to moderately ill:
Fluoroquinolones (FQ) are reasonable empiric choices if patient has not received a FQ in recent past, is not from a
long-term care facility (LTCF), and FQ resistance is low as per local antibiogram (< 20%).
Levofloxacin 500mg IV/PO q24
Ciprofloxacin 500mg PO twice daily or 400mg q 8-12h IV
If patient severely ill or received recent FQ or from LTCF: select broad empiric coverage.
Due to increasing antibiotic resistance, up-to-date knowledge of local sensitivity patterns is critical for choosing the
optimal empiric regimen.
Note that all of the listed agents must be adjusted for renal insufficiency if present.
Cefepime 2g IV q12 hrs
Ceftazidime 2g IV q8 hrs
Ceftazidime/avibactam 2000mg/500mg IV q8h
Ceftolozane/tazobactam 1500mg IV q8h
Imipenem 500 mg IV q 6 hrs
Meropenem 1g IV q8 hrs
Doripenem 500 mg IV q8 hrs
Piperacillin/tazobactam 3.375-4.5g IV q6 hrs
If patient severely ill and urine gram stain shows gram (+) cocci: consider adding vancomycin empirically.
Once culture and sensitivity available, switch to narrow spectrum as much as feasible.
Duration of treatment:
European guidelines recommend stopping treatment 3 to 5 days after either defervescence or elimination of the
complicating factor (e. g., catheter or stone).
Shorter courses (7 days) reasonable if patient improves rapidly.
Longer courses (10-14 days) reasonable if severe initial presentation or patient has a delayed response.
Surgical intervention and urinary devices
If ureteral or renal pelvic obstruction is present and cannot be quickly relieved, urology or interventional radiology
consultation strongly advised (urgent if patient is critically ill).
Intermittent catheterization is preferable to an indwelling catheter whenever possible.
The use of sterile vs. non-sterile ("clean") technique with intermittent catheterization makes no difference in UTI
rates.
Pts with condom catheters have fewer UTIs than those patients with indwelling catheters (.08 vs. .21 UTIs per patient-
month).
Candidates for condom catheters must be alert and have intact skin.
If indwelling catheter needed, removal and replacement (as compared with retention of initial catheter) results in more
rapid defervescence and lower risk of short-term symptomatic relapse
Prevention of cUTI
Evidence-based effective measures include:
Aseptic catheter insertion
Maintaining a closed system
Avoiding obstruction or back-flow
Removing catheter as soon as possible
Either a computer-driven or pre-printed prompt system to regularly assess the need for urinary catheters may reduce
catheter use in hospital or SNF settings.
See www.ahrq.gov/cautitools or www.catheterout.org for related information
Bladder scanning whenever bladder distension is suspected may help avoid unnecessary catheter insertions.
Measures without good evidence of benefit:
Meatal cleaning
Antibiotics in the Foley bag
Long-term preventive antibiotic therapy may be considered for individual patients with no evident alternatives but should
be viewed as an option of last resort due to risks of collateral damage and long-term failure with increasingly antibiotic-
resistant organisms. Renal transplant patients in the post-op period are an exception and may benefit from prophylaxis.

3. Selected Drug Comments
Drug Recommendation
Ampicillin Although recommended in older reviews, current resistance patterns make this abx a poor
choice for empiric therapy.
Aztreonam Reasonable empiric choice in patients with rash or immediate hypersensitivity to penicillin. For
severely ill patients, combine with a second agent (e.g., ciprofloxacin).
Cefepime Adequate empiric choice in severely ill patients if risk of ESBL producing organism is low. Avoid
if risk of ESBL producer is high (e. g., resident of LTCF, hospital associated). Covers
Pseudomonas. Can be used in pts with penicillin allergy if reaction was not Type I - immediate
hypersensitivity.
Ceftazidime Adequate empiric choice in severely ill pts if risk of ESBL producing organism is low. Avoid if risk
of ESBL producer is high (e.g., resident of LTCF, hospital associated). Covers most strains of
Pseudomonas. Can be used in pts with penicillin allergy if reaction was not Type I - immediate
hypersensitivity.
Ceftazidime/avibactam FDA-approved for treatment of cUTI. Active against ESBL-producing organisms as well as KPC-
producing organisms, but not against metallo-β-lactamases (e.g., NDM). Nearly no Gram-
positive activity. Reserve for treatment of extensively drug-resistant infections.
Ceftolozane/tazobactam FDA-approved for treatment of cUTI. Novel structure associated with enhanced Gram-negative
activity. Active against ESBL-producing organisms but not KPC- or NDM-producers. Has Gram-
positive activity. Reserve for treatment of extensively drug-resistant infections.
Ciprofloxacin Appropriate for empiric coverage in mild to moderate illness. A concern is overall rising rates of
resistance in community and hospitals, especially resistance in pts who have recently received a
fluoroquinolone.
Gentamicin Sometimes added to beta-lactams for synergy and to broaden coverage. More toxic than other
available agents, especially in the elderly and those with chronic renal insufficiency. Should not
be used as monotherapy for moderate-to-severe infections. I avoid aminoglycosides unless
limited by drug resistance or pt. allergies.
Imipenem/cilastatin Excellent empiric coverage in severely ill pts. Covers most strains of Pseudomonas. Can be
used in pts with penicillin allergy if reaction was not Type I - immediate hypersensitivity.
Levofloxacin Appropriate for empiric coverage in mild to moderate illness. Watch for resistance in pts who
have recently received a fluoroquinolone.
Meropenem Excellent empiric coverage in severely ill pts. Covers most strains of Pseudomonas. Can be
used in pts with penicillin allergy if reaction was not Type I - immediate hypersensitivity.
Nitrofurantoin Appropriate only for lower tract infections in the mildly ill since there no sufficient systemic levels
of drug achieved. Avoid in renal insufficiency. Do not use for pyelonephritis. May be effective in
cases with VRE.
Piperacillin/tazobactam Excellent empiric coverage in severely ill pts. Covers most strains of Pseudomonas.
Vancomycin May be added if gram-positive organisms are suspected clinically or based on gram stain.
Moxifloxacin Limited urinary excretion. Do NOT use for UTI.
Doripenem Excellent empiric choice in severely ill pts. Covers most strains of Pseudomonas. Can be used
in pts with penicillin allergy if reaction was not Type I - immediate hypersensitivity.
FOLLOW UP
Infectious diseases consultation is advised if unusual pathogens are identified or if the patient fails to respond to therapy.
Follow up cultures are NOT required if the pt is clinically improving.
OTHER INFORMATION
Culture and sensitivity are mandatory. The wide array of pathogens and increasing abx resistance often result in
ineffective empiric treatment.
Only perform urine culture if patient is symptomatic.

4. Culturing asymptomatic bacteruria leads to unnecessary antibiotic use.
Renally excreted agents are always preferable when treating UTI
Pathogen Specific Therapy
Pathogen 1st Line Agent 2nd Line Agent
Pseudomonas
aeruginosa
Ceftazidime
Cefepime
Piperacillin/tazobactam, ceftazidime/avibactam, ceftolozane/tazobactam,
ciprofloxacin, doripenem, imipenem, meropenem
Enterobacteriaceae Ciprofloxacin
Levofloxacin
Ceftazidime, cefepime, piperacillin/tazobactam, trimethoprim/sulfamethoxazole,
doripenem, imipenem, meropenem,
Acinetobacter spp. Imipenem Ciprofloxacin, ampicillin/sulbactam, colistin
Methicillin-resistant
Staphylococcus
aureus
Vancomycin Trimethoprim/sulfamethoxazole, linezolid
Vancomycin-
resistant
enterococcus (VRE)
Nitrofurantoin
(lower tract
infection only)
Linezolid, daptomycin, ampicillin (if susceptible), fosfomycin (lower tract infection
only)
Candida albicans Fluconazole Amphotericin B deoxycholate (ID consultation recommended), 5-FC (may be
used as monotherapy in non-severely ill patients with fluconazole-resistant
infection)
Basis for recommendation
1. Hsueh PR, Hoban DJ, Carmeli Y, et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of
complicated urinary tract infections in Asia-Pacific region. J Infect. 2011;63(2):114-23. [PMID:21669223]
Comment: Reviews empiric antibiotic options in face of increasing resistance.
2. Rebmann T, Greene LR. Preventing catheter-associated urinary tract infections: An executive summary of the Association
for Professionals in Infection Control and Epidemiology, Inc, Elimination Guide. Am J Infect Control. 2010;38(8):644-6.
[PMID:20868930]
Comment: Executive summary of APIC guidelines for preventing catheter associated UIIs. The complete guideline is available at
www.apic.org.
3. Bader MS, Hawboldt J, Brooks A. Management of complicated urinary tract infections in the era of antimicrobial
resistance. Postgrad Med. 2010;122(6):7-15. [PMID:21084776]
Comment: Emphasizes difficulty of empiric antibiotic selection due to increasing resistance.
4. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract
infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin
Infect Dis. 2010;50(5):625-63. [PMID:20175247]
Comment: Evidence based guidelines for catheter associated infections.
5. Naber KG, Bergman B, Bishop MC, et al. EAU guidelines for the management of urinary and male genital tract infections.
Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology
(EAU). Eur Urol. 2001;40(5):576-88. [PMID:11752870]
Comment: European guidelines for the diagnosis and treatment of uncomplicated and complicated UTIs.
6. Lundstrom T, Sobel J. Nosocomial candiduria: a review. Clin Infect Dis. 2001;32(11):1602-7. [PMID:11340532]
Comment: An excellent review of the issues surrounding candiduria.
References
7. Wagenlehner FM, Sobel JD, Newell P, et al. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated
Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect
Dis. 2016;63(6):754-62. [PMID:27313268]

5. Comment: Phase III trial demonstrating non-inferiority of ceftazidime-avibactam to doripenem for treatment of cUTI. Patients with
acute pyelonephritis were included in the denominator.
8. Wagenlehner FM, Umeh O, Steenbergen J, et al. Ceftolozane-tazobactam compared with levofloxacin in the treatment of
complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI).
Lancet. 2015;385(9981):1949-56. [PMID:25931244]
Comment: Phase III trial demonstrating non-inferiority of ceftolozane-tazobactam to levofloxacin for treatment of cUTI. Patients with
acute pyelonephritis were included in the denominator.
9. Levison ME, Kaye D. Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative
uropathogens. Curr Infect Dis Rep. 2013;15(2):109-15. [PMID:23378123]
Comment: Emphasizes the increasing challenge of treatment due to drug resistance.
Rating: Important
10. Niël-Weise BS, van den Broek PJ, da Silva EM, et al. Urinary catheter policies for long-term bladder drainage. Cochrane
Database Syst Rev. 2012. [PMID:22895939]
Comment: The cited references are mostly reviews rather than clinical trials or community based surveillance reports. Consider also
adding the European Urology Association guidelines as a reference and including as "basis of recommendation" should you feel that
this is indicated. Some suggested reports of trials have been added for your consideration. European guidelines added as
suggested.Review of the literature regarding catheter placement policies and antibiotic prophylaxis. Interesting for how little is
actually known.
11. Chant C, Smith OM, Marshall JC, et al. Relationship of catheter-associated urinary tract infection to mortality and length
of stay in critically ill patients: a systematic review and meta-analysis of observational studies. Crit Care Med.
2011;39(5):1167-73. [PMID:21242789]
Comment: Underscores the importance of reducing catheter associated infections in the hospital
Rating: Important
12. Tenke P, Kovacs B, Bjerklund Johansen TE, et al. European and Asian guidelines on management and prevention of
catheter-associated urinary tract infections. Int J Antimicrob Agents. 2008;31 Suppl 1:S68-78. [PMID:18006279]
Comment: An attempt at evidence based guidelines for catheter insertion and care.
Rating: Important
13. Crouzet J, Bertrand X, Venier AG, et al. Control of the duration of urinary catheterization: impact on catheter-associated
urinary tract infection. J Hosp Infect. 2007;67(3):253-7. [PMID:17949851]
Comment: A prompt system to regularly assess the need for a urinary catheter can reduce usage and infections.
Rating: Important
14. Nicolle LE, AMMI Canada Guidelines Committee*. Complicated urinary tract infection in adults. Can J Infect Dis Med
Microbiol. 2005;16(6):349-60. [PMID:18159518]
Comment: Outstanding, comprehensive review, including summary of relevant clinical trials and evidence-based recommendations
for diagnosis, treatment, and prevention. Highlights the complexity of the topic and emphasizes the importance of decision-making
based upon individual patient characteristics.
Rating: Important
15. Hoepelman AI, Meiland R, Geerlings SE. Pathogenesis and management of bacterial urinary tract infections in adult
patients with diabetes mellitus. Int J Antimicrob Agents. 2003;22 Suppl 2:35-43. [PMID:14527769]
Comment: Broad overview of urinary tract problems in the diabetic patient.