Urinary Tract Infections in Adults

UK HealthCare

Guideline for the Management of Urinary Tract Infections in Adults

Antimicrobial Stewardship Subcommittee · Pharmacy and Therapeutics Committee · University of Kentucky Health Care

Authors	Antimicrobial Stewardship Subcommittee
Target Population	Adult patients with suspected urinary tract infections
Overview	Evidence-based management of suspected urinary tract infections.
Effective Date	7/1/2018
Revised	10/17/2023
Expiration	10/17/2025 · Reviewed every 2 years
Primary Outcome	Treatment of asymptomatic urinary conditions to assess the rate of inappropriate antibiotic use.

Purpose of Guidelines

To provide evidence-based guidelines for the appropriate management of adults 18 years and older with urinary tract infections (UTIs) presenting to the Emergency Department or admitted to UK HealthCare (UKHC).

Background

Multiple guidelines have been published for the diagnosis, prevention, and treatment of urinary tract infections, one of the most common indications for antimicrobials. In 2019, the Infectious Diseases Society of America (IDSA) published a guideline describing diagnosis and treatment of asymptomatic bacteriuria (ASB).¹ An updated guideline published by IDSA in 2010 highlighted the diagnosis, prevention, and treatment of catheter-associated urinary tract infections (CA-UTI).² The IDSA and the European Society for Microbiology and Infectious Diseases (ESCMID) published an updated guideline in 2011 for the treatment of uncomplicated cystitis and pyelonephritis in women.³ Taken together, these guidelines emphasize appropriate management of urinary tract infections.

Antimicrobial stewardship principles associated with urinary tract infection management

• Patients should NOT be treated for UTIs in the absence of typical symptoms, such as frequency, urgency, dysuria, or suprapubic pain (see Table 4 for a full list of qualifying symptoms).
  • A UTI diagnosis should involve the patient presenting with 1) typical UTI symptoms as stated above, 2) a urinalysis (UA) with WBCs >10 and 3) a positive urine culture from an appropriately obtained specimen.
  • Due to a UAs low positive predictive value but high negative predictive value, a positive UA alone DOES NOT indicate a UTI.
  • Other disease states such as malignancy, sexually transmitted infections, overactive bladder and benign prostatic hyperplasia can mimic a UTI, so all 3 diagnostic criteria should be met before initiating antimicrobial therapy.
• A commonly over-treated condition is asymptomatic bacteriuria (ASB), defined by the IDSA as the isolation of ≥ 10⁵ colony-forming units (CFU)/mL of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection. ASB is also a common finding, affecting up to 50% of women over the age of 60.¹
  • The treatment of ASB has been associated with significant harm with little to any benefit to our patients.
  • Treatment of ASB involves inappropriate antimicrobial use that is often associated with collateral damage such as increased adverse effects, increased antimicrobial resistance, increased risk for the development of subsequent UTIs, overall increase in health-care associated costs, and Clostridioides difficile-associated diarrhea^1,10.

Table 1: IDSA UTI Screening / ASB Treatment Recommendations

Recommendation	Patient Population
No recommendation for or against	Renal transplant patients High-risk neutropenic patients
Recommend against	Non-pregnant females Functionally impaired patients Diabetic patients Acute mental status change Patients with a recent fall Older patients who reside at home or in longterm care facilities Spinal cord injury patients Short-term and long-term indwelling urethral catheters Nonrenal transplant patients
Recommend for	Pregnancy: ASB carries an increased risk of pyelonephritis, premature delivery, and low birth weight of the infant Preparation for a planned urinary tract procedure (e.g. transurethral resection of the prostate, TURP): patients with ASB and undergoing procedures with a high probability of mucosal bleeding are at an increased risk of bacteremia

Candiduria

• Isolating Candida species in the urine without signs or symptoms of a urinary tract infection almost always represents colonization and SHOULD NOT be treated with antifungal therapy⁶.
  • According to the IDSA, in asymptomatic patients with a UA or urine culture positive for a Candida species, it is recommended to eliminate predisposing factors (such as indwelling catheters) to resolve candiduria.
  • The IDSA also recommends that asymptomatic candiduria should only be treated in the following patient populations:
    • Neutropenic patients (defined as ANC <100 cells/mm³ for ≥7 days duration following chemotherapy)
    • Patients who have or will undergo a urologic procedure

Altered Mental Status

• Altered mental status in the absence of genitourinary symptoms or other signs of systemic infection (fever or hemodynamic instability) is not indicative of a UTI.
  • The IDSA guidelines recommend against screening for or treating ASB in elderly patients that present with isolated altered mental status, regardless of the patient's age¹.
  • Providers should assess for other causes of altered mental status and avoid initiating antimicrobials. Other causes include: dementia, dehydration, hospital acquired delirium, psychiatric disorders, vitamin deficiencies, medications, severe hypoxia or hypertension, and hepatic or uremic encephalopathy.
  • Internal data from UK HealthCare, show that ~80% of patients that presented with altered mental status and were treated for a UTI did not meet criteria for treatment as determine by Loeb Minimum Criteria.

Table 2: Definitions of Urinary Tract Infections

Term	Definition
Pyuria	Presence of increased numbers of polymorphonuclear leukocytes in the urine; evidence of an inflammatory response in the urinary tract (WBC ≥ 10 HPF or Leukocyte Esterase ≥ Small).
Fever	Adults: Single oral temperature ≥ 38.3°C (101.0°F) or oral temperature of ≥ 38.0°C (100.4°F) for ≥ 1 hour or twice in 24 hours.
Cystitis	Clinical syndrome involving dysuria, frequency, and/or urgency associated with the lower urinary tract.
Acute Uncomplicated Cystitis	Symptomatic bladder infection characterized by frequency, urgency, dysuria, or suprapubic pain in a woman with a normal urinary tract, and it is associated with both genetic and behavioral determinants.
Complicated Cystitis	Symptomatic urinary infection in individuals with functional or structural abnormalities of the urinary tract. Male gender automatically constitutes complicated due to the rarity of UTIs without an abnormality.
Acute Pyelonephritis	Renal infection characterized by costovertebral angle (CVA) pain and/or tenderness, often with fever; it occurs in the same population that experiences acute uncomplicated urinary infection and may present with dysuria, frequency, and/or urgency.
Catheter-Associated Urinary Tract Infection (CA-UTI)	Any form of UTI noted above (acute uncomplicated or complicated cystitis or acute nonobstructive pyelonephritis) in the presence of an indwelling urinary catheter.
Asymptomatic Bacteriuria (ASB)	Isolation of ≥ 105 colony-forming units (CFU)/mL of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection.
Relapse	Recurrent urinary tract infection after therapy resulting from persistence of the pretherapy isolate in the urinary tract. Typically occurs within 2 weeks after the most recent infection due to unsuccessful treatment, a resistant organism, or anatomical abnormalities.
Reinfection	Recurrent urinary tract infection with an organism originating from outside of the urinary tract, either a new bacterial strain or a strain previously isolated that has persisted in the colonizing flora of the gut or vagina. Typically occurs greater than 2 weeks after the most recent infection and should be treated as a new infection.

The management of infections or clinical syndromes not listed above, such as renal abscesses or emphysematous pyelonephritis, is outside the scope of this guideline.

Table 3: Common Pathogens Isolated from Urine Cultures

Community-Acquired	Hospital-Acquired
Escherichia coli Staphylococcus saprophyticus Klebsiella pneumoniae Proteus spp.	Escherichia coli Proteus spp. Klebsiella pneumoniae Enterobacter spp. Pseudomonas aeruginosa Staphylococcus spp. Enterococcus spp. Candida spp.a

^a Candida spp. are rarely a clinically significant isolate in urinary tract infections.

Table 4: Indications for Obtaining a Urinalysis and/or Urine Culture at UKHC

Any of the following:

• Unexplained suprapubic pain
• Unexplained flank pain
• Dysuria
• Urinary urgency
• Increased urinary frequency
• Septic shock without another cause
• Spinal cord injury patient with new or worsening spasticity, autonomic hyperreflexia, malaise, lethargy, or sense of unease
• Unexplained altered mental status after history and physical obtained
• Fever in the following patient populations:
  • Neutropenic
  • Kidney transplant recipient
  • Pregnant
  • Known urinary tract obstruction
  • Post urologic procedure
  • <2 years old with risk factors

Note: Fever without one of the findings above is not an indication for urinary assessment of infection.

Figure 1: Adult ED & Inpatient Urinalysis and Urine Culture Algorithm

Figure 2: Adult Diagnosis & Empiric Treatment Algorithm

Empiric treatment recommendations are based on susceptibility rates of common UTI organisms per the UKHC antibiogram. Other considerations should include patient colonization, previous infections, and prior antimicrobial exposure in the previous 3 months when selecting antibiotics.

Indication Present from Figure 1 and Table 4^a

Acute Uncomplicated Cystitis

Community-Acquired

Oral options:

First line: Nitrofurantoin (avoid if CrCl <30 mL/min)

Cefadroxil or Cephalexin^b

Fosfomycin

IV options: Ceftriaxone (Penicillin IgE-mediated allergy: consider Aztreonam)

Healthcare- or Hospital-Acquired

Antipseudomonal β-lactam ± an Aminoglycoside

Acute Complicated UTI

Includes: men; women with an abnormal lower urogenital tract; acute nonobstructive pyelonephritis; CA-UTI

Community-Acquired

Oral options: Ceftriaxone ×1 dose, followed by one of:

• Inpatient or discharged from ED: Cefadroxil or Cephalexin^b (Penicillin IgE allergy: consider Levofloxacin)

• Absence of upper tract involvement: Fosfomycin

IV options: Ceftriaxone (Penicillin IgE allergy: consider Aztreonam)

Healthcare- or Hospital-Acquired

Antipseudomonal β-lactam ± an Aminoglycoside

^a Risk factors for healthcare-associated UTI include any of the following in the past 90 days: IV or oral antibiotics, and hospitalization of five or more days prior to the occurrence of UTI.   ^b Can consider cefdinir if the patient has an allergy (such as rash) that precludes the use of an oral first-generation cephalosporin or penicillin.

Definitive and Pathogen-Specific Therapy

Trimethoprim/sulfamethoxazole (TMP/SMZ) and levofloxacin are preferred for pyelonephritis if organism is susceptible.

Table 4: Recommended Antimicrobials for Selected Pathogens at UKHC

Pathogen	Therapy Following Organism Identification	Therapy Following Susceptibility Results
EnterobacteralesCommon: E. coli, Klebsiella pneumoniae, Proteus mirabilis	See Figure 2	TMP/SMZ OR Cefazolin/Cephalexin OR Ampicillin/Amoxicillin (narrowest susceptible antibiotic)
ESBL-Producing EnterobacteralesCommon: E. coli, Klebsiella spp., P. mirabilis	Meropenem	Meropenem OR TMP/SMZ OR Levofloxacin/Ciprofloxacin OR Aminoglycosidea OR Fosfomycinc/Nitrofurantoin (lower tract only)
AmpC-Producing EnterobacteralesCommon: Enterobacter cloacae complex, Klebsiella aerogenes, Citrobacter freundii	Cefepime	Cefepime OR TMP/SMZ OR Levofloxacin/Ciprofloxacin OR Fosfomycin (lower tract only) OR Aminoglycosidesa
Pseudomonas aeruginosa	Piperacillin/tazobactam OR Cefepime. Consider Tobramycina	Antipseudomonal β-lactamb OR Levofloxacin OR Aminoglycosidesa
Carbapenem-Resistant OrganismsResistance profile usually unknown until susceptibilities return; base therapy on history of resistant pathogens and severity of illness	Assess prior culture history to determine optimal empiric therapy. See options at right, based on upper or lower tract involvement.	Uncomplicated Cystitis: Levofloxacin/Ciprofloxacin, TMP/SMZ, Nitrofurantoin, Aminoglycosidea. Complicated UTI or Pyelonephritis: Levofloxacin/Ciprofloxacin or TMP/SMZ preferred. Aminoglycosidesa, Ceftazidime-avibactam, Meropenem-vaborbactam, Imipenem-cilastatin-relebactam, or Cefiderocol are alternatives (use requires AST approval).
MRSARarely a true cause of UTI. Without an indwelling catheter, consider hematogenous spread and draw blood cultures	Vancomycin	Vancomycin OR TMP/SMZ
Enterococcus spp.	Ampicillin	Ampicillin or Amoxicillin
VREVancomycin-Resistant Enterococcus spp.	Lower tract: Ampicillin OR Fosfomycin. Upper tract: Linezolid	Lower tract: Ampicillin OR Fosfomycin. Upper tract: Linezolid
Candida spp.Rarely a true cause of UTI. If asymptomatic, consider colonization	Eliminate predisposing factors (e.g., remove and/or replace indwelling catheters)	If necessary to treat: Fluconazole OR Amphotericin B deoxycholated

^a Assuming normal renal function: amikacin 15 mg/kg or gentamicin/tobramycin 5 mg/kg IV once for Enterobacterales cystitis (use dosing body weight in obesity). Per 2023 CLSI breakpoints, tobramycin and amikacin are the only aminoglycosides recommended for Pseudomonas aeruginosa UTIs.
^b Antipseudomonal β-lactams: aztreonam, cefepime, meropenem, piperacillin/tazobactam. If resistant to others, may require ceftolozane-tazobactam.
^c IDSA recommends against fosfomycin for infections caused by K. pneumoniae and several other Gram-negative organisms that frequently carry fosA hydrolase genes (may lead to clinical failure). Susceptibility testing should be performed for organisms other than E. coli before using fosfomycin.
^d Amphotericin B deoxycholate achieves urine concentrations exceeding MICs for most isolates; lipid formulations do not achieve adequate urine concentrations and should not be used.

Table 5: Definitive Treatment Options for Adult Patients

Only use if the pathogen is susceptible on culture results and the agent is appropriate for the infection type. Dosing assumes normal renal function and BMI — consult a pharmacist for dosing in renal impairment or obesity.

Antimicrobial Agent	Uncomplicated Cystitis	Complicated Cystitis	CA-UTI	Pyelonephritise
Ampicillin 1 g IV Q6ha; Ceftriaxone 2 g IV Q24h; Cefepime 2 g IV Q12hb; Piperacillin/tazobactam 3.375 g IV Q6hb; Meropenem 1 g IV Q8hb	3 days	5 days	5 days	7 days
Amoxicillin 500 mg PO Q8hc; Cephalexin 500 mg PO Q6hc,g; Cefadroxil 1000 mg PO Q12hc,d,g; Cefdinir 300 mg PO Q12hc,g	5 days	7 days	7 days	10 days
Levofloxacin 750 mg PO/IV Q24h	3 days	5 days	5 days	5 days
TMP/SMZe 160/800 mg PO Q12h	3 days	7 days	7 days	10 days
Fosfomycin 3 g PO	1 dose	Q48h × 3 doses	Q48h × 3 doses	Avoid use
Nitrofurantoin monohydrate/macrocrystals 100 mg PO Q12h	5 days	Avoid use	Avoid use	Avoid use
Amikacin 15 mg/kg IV dailyh; Gentamicin 5 mg/kg IV dailyh; Tobramycin 5 mg/kg IV dailyh	1 dose	1 dose, with subsequent doses and dosing interval based on pharmacokinetic evaluation
Fluconazole 200 mg (or 3 mg/kg) PO Q24hf	14 days	14 days	14 days	14 days
Amphotericin B deoxycholate 0.5 mg/kg IV Q24h	1–7 days	1–7 days	1–7 days	1–7 days

^a 7 days of therapy is recommended when using ampicillin to treat uncomplicated VRE cystitis. ^b Use extended infusion over 3 hrs for Gram-negative pathogens causing severe infection; consider cefepime 2 g IV q8h and meropenem 2 g IV q8h. ^c Amoxicillin, cephalexin, cefadroxil, and cefdinir are oral β-lactam agents on the UKHC formulary. ^d Cefadroxil 500 mg PO q12h can be used for acute uncomplicated cystitis. ^e Pregnant patients with pyelonephritis should be treated for 14 days assuming prompt clinical improvement. ^f Consider 200–400 mg (6 mg/kg) daily for pyelonephritis. ^g Cefazolin susceptibility in E. coli, K. pneumoniae, and P. mirabilis can be used as a surrogate to predict susceptibility for all oral cephalosporins. ^h Aminoglycosides for pyelonephritis or complicated UTIs should only be used if therapeutic drug monitoring is available in a timely manner. AUC/MIC ratio of 80–100 preferred; alternatively target peak/MIC ratio of 8–10. Use dosing body weight in obesity.

Table 6: Antimicrobial Options for Pregnant Patients

Antimicrobial Agent	1st Trimester	2nd Trimester	3rd Trimester
All β-lactamsa	Appropriate for use	Appropriate for use	Appropriate for use
Fosfomycin	Appropriate for use	Appropriate for use	Appropriate for use
Nitrofurantoinb	Use if no other options	Appropriate for use	May be appropriatec
TMP/SMZb	Use if no other optionsd	Appropriate for use	May be appropriated
Levofloxacin	Use if no other options	Use if no other options	Use if no other options
Amphotericin B deoxycholate	Appropriate for use	Appropriate for use	Appropriate for use
Fluconazolee	Avoid use	May be appropriatee	May be appropriatee

^a When appropriate, β-lactams are preferred (no association with prenatal exposure and birth defects). ^b Nitrofurantoin and TMP/SMZ are contraindicated in patients with G6PD deficiency, or in pregnant women at risk of this condition. ^c Possible increased risk of neonatal jaundice in the last 30 days of pregnancy. ^d Supplemental folic acid should be used in the first trimester; avoid at term due to concern for kernicterus. ^e Malformations noted with ≥400 mg/day in the first trimester; may consider use in later trimesters at low doses for short courses.

Other Considerations for ADULT Patients

The standard duration of therapy for urinary tract infections is dependent on the type of infection.

• Immunocompromised patient populations
  • Optimal duration of therapy for urinary tract infections has not been determined.
• Concomitant bacteremia
  • Patients with Gram negative bacilli bacteremia secondary to urinary tract infections should be treated for 7 days, with a start date of culture positivity (assuming appropriate therapy started on or before the same day).
  • If Staphylococcus aureus is isolated, suspicion should increase for hematogenous dissemination from another source to the urinary tract and management should follow recommendations from the "Staphylococcus aureus Bacteremia Treatment Guideline for Adults" at https://antimicrobial.ukhc.org/adult/.

Appendix A: UTI Orders and Workflow within Epic

UTI Workup Diagnostic Testing Options and Details

1. Urinalysis, manual only
2. Urinalysis microscopic
3. Urinalysis with reflex to microscopic – reflexes when the following criteria are met:
   • Protein ≥ 300 mg/dL
   • Presence of blood or leukocytes
   • Nitrite positive
4. Urine culture
5. Urinalysis with reflex to microscopic and culture – primary test that should be ordered upon suspicion of a UTI
   • 2 Specimens should be sent upon ordering
   • Manual UA (dipstick) will reflex to microscopic urinalysis if above criteria are met
   • If microscopic urinalysis evaluation demonstrates WBC > 10/HPF, will reflex to urine culture

Urinalysis with Reflex to Microscopic and Culture

1. Indications will be present to guide assessment of clinical symptoms.
2. The order will initially appear as 3 separate lines. One for the urinalysis with reflex microscopic and culture that is made up of the urine gray (urine culture) and urinalysis with reflex microscopic. As the individual orders update, the overall order will as well. Once the result has finalized, only the final urinalysis with reflex microscopic and culture should appear.
3. If the urinalysis microscopic criteria are NOT met (WBC ≤ 10/HPF) then the urine culture will not be processed since inflammation (pyuria) is not present making a UTI highly unlikely. (Result component displays: "Reflex urine culture not indicated.")
4. If the urinalysis microscopic criteria are met (WBC > 10/HPF) then the urine culture will be processed. (Result component displays: "Sent for Culture.")

The original guideline includes Epic interface screenshots illustrating steps 1–4 above. Those screenshots are not reproduced here; the accompanying text is presented verbatim.

References

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8. Shah KJ, Cherabuddi K, Shultz J, Borgert S, Ramphal R, Klinker KP. Ampicillin for the treatment of complicated urinary tract infections caused by vancomycin-resistant Enterococcus spp (VRE): a single-center university hospital experience. Int J Antimicrob Agents. 2018; 51(1):57-61.
9. Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; July 30, 2021. https://online.lexi.com. Accessed May 17, 2022.
10. Advani SD, Polage CR, Fakih MG. Deconstructing the urinalysis: A novel approach to diagnostic and antimicrobial stewardship. Antimicrob Steward Healthc Epidemiol. 2021;1(1):e6. doi: 10.1017/ash.2021.167.
11. Urinary Tract Infections in Pregnant Individuals. Obstet Gynecol. 2023 Aug 1;142(2):435-445. doi: 10.1097/AOG.0000000000005269. PMID: 37473414.

UK HealthCare · Antimicrobial Stewardship Subcommittee · Effective 7/1/2018, Revised 10/17/2023, Expires 10/17/2025
Guideline approved by the Antimicrobial Stewardship Team Subcommittee and Pharmacy and Therapeutics Committee