Urinary Tract Infections

Please note that this guide goes with current guidelines, but current guidelines don’t really meet practice. IDSA is due with new guidelines in 2024 and a preview was presented at IDweek in 2023/ECCMID 2024. It will change the definition of complicated UTIs to include pyelonephritis, catheter-associated UTI (CAUTI), UTI with fever or other evidence of systemic or upper tract infection and uncomplicated UTI to be everything else. Classically guidelines suggest all UTI in men are complicated, but that’s not the case (must look for prosthetic involvement). See slides at the end of this.

The selection of empiric antibiotics for complicated UTI will include a four-step process. Clinicians should review (1) severity of illness, (2) risk factors for resistant organisms, (3) patient factors, and (4, only if septic) antibiogram. Preferred agents: fluoroquinolones, 3rd/4th generation cephalosporins, piperacillin-tazobactam, (if septic) carbapenems. A 7 day duration is recommended rather than a longer course if clinical improvement is demonstrated.

These are not CURRENT guidelines, but may be current practice.

When presented with a urinary tract infection, you have to ask:

Cystitis or pyelonephritis?
- Lower UTI – cystitis: dysuria, frequent urination, urgency, suprapubic pain, hematuria
- Upper UTI – pyelonephritis: same as above plus systemic symptoms like fever chills, flank pain, CVA tenderness, nausea and vomiting
Complicated or Uncomplicated
- Complicated: associated with a structural or functional abnormality of the urinary tract or significant medical or surgical comorbidities: indwelling foley catheter, ureteral stents, prostatic hyperplasia, nephrolithiasis, tumor, fibrosis, urethral stricture, voiding disorders like neurogenic bladder or intrinsic renal disease,
- Also consider if patient has recent hospitalization, pregnancy, history of childhood UTI, recent antimicrobial use, immunosuppression
- Recurrent cystitis: an infection within 14 days of the previous antibiotic discontinuation
Most frequent causes of UTI include: E. coli, K. pneumoniae, S. saprophyticus, Enterococcus spp, Group B Strep, Proteus mirabilis, Pseudomonas, S. aureus, Candida

Diagnosis:

Not diagnostic symptoms:

Altered mental status (AMS)
Falls
Malodorous or cloudy urine
Urinalysis (UA) alone
Bacteriuria alone
Leukocyte esterase, nitrites or urine wbc do not
diagnose UTI

Pyuria (“pus” in urine) and bacteriuria (bacteria in urine) are common findings in patients:
% of patients with pyuria (Am J Infect Control. 2017;45(10):1143-1153.)
Young women – 32%
Pregnant women – 30-70%
Women with diabetes – 70%
Elderly institutionalized patients- 90%
Dialysis patients – 90%
Short-term catheters – 30-75%
Long-term catheters – 50-100%

Percent of people with bacteriuria:
Premenopausal women 1-5%
Women 70-90 years old 11-16%
Long-term care residents 15-50%
Females with diabetes 9-29%
Males with diabetes 1-11%
Dialysis patients 25%
Chronic indwelling catheters >90%

These are not diagnostic without symptoms.

Treatment:

Asymptomatic Bacteriuria:

DO NOT TREAT ASYMPTOMATIC BACTERIURIA unless your patient is a pregnant women or patient undergoing urologic procedures. All pregnant women should be treated for a positive urine bacteria screen regardless of symptoms. Treatment decreases the risk of pyelonephritis, preterm labor, and low birth weight.

Screening only recommended for asymptomatic people if pregnant or undergoing Transurethral resection of the prostate (TURP) or bladder, ureteroscopy, including lithotripsy, percutaneous nephrolithotomy/nephrolithotripsy.

Treatment of ASB increases the risk for subsequent symptomatic UTI. (Clin Infect Dis. 2019;68(10):e83-e110. JAMA Intern Med. 2017;177(9):1308–1315. Neurosurgery. 2019;85(5):664-671. Clin Infect Dis. 2012;55(6):771-777).

Uncomplicated UTI:

Treat based on microbiology when possible.

If inpatient, IV antibiotics are preferred initially, but may transition within 72 hours if improvement. Outpatients usually can be managed orally.

Uncomplicated cystitis (1, 3, 5):
- Bactrim BID for 3 days (only if local resistance <20%)
- Nitrofurantoin 100 mg BID * 5 days ONLY FOR CYSTITIS doesn’t work systemically, only for CrCl >20-30
- Fosfomycin 3 g for 1 dose
- Second line:
  - Fluoroquinolone like Cipro or Levaquin for 3 days if persistent. Avoid if other options.
  - Beta-lactam for 3-7 days (usually 5 days)
Uncomplicated pyelonephritis:
- outpatient:
  - Ciprofloxacin 500 mg orally twice daily for 7 days or levofloxacin 750 mg orally daily for 5 days if resistance rates are <10%
  - If >10% FQ resistance, IV ß-lactam or aminoglycoside is recommended to start
  - Bactrim orally twice daily for 14 days
  - Oral ß-lactam antibiotics after a single dose of IV ß-lactam or aminoglycoside for 10-14 days
- IV Beta-lactam is preferred initially if patient presents with systemic symptoms and hospitalization is required

When uropathogen resistance is greater than 10%, use an initial dose of ceftriaxone or an aminoglycoside

Complicated UTI:

For complicated UTIs associated with urinary instrumentation or obstruction, remove if possible.

Complicated UTI
- Source control is the best treatment: Relieve obstruction, exchange catheters, drain infected fluid collections
- Intravenous therapy is preferred initially for patients requiring hospitalization:
- Treat based on local resistance for 7-14 days, longer if no source control
- fluoroquinolone for 5 days (Levofloxacin 750 mg every 12 hr)
- aminoglycoside for 14 days
- extended-spectrum beta-lactam for 7-14 days (usually ceftriaxone)
Pregnancy
- 3-7-day treatment
- amoxicillin 500 mg every 8 hours
- nitrofurantoin 100 mg every 12 hours – good for severe PCN allergy
- cephalexin 500 mg every 6 hours, cefpodoxime 100 mg every 12 hours, or cefuroxime 250 mg every 12 hours
- fosfomycin 3 g as a single dose
- avoid FQs, tetracyclines, aminoglycosides, and Bactrim in last trimester due to folate antagonism
recurrent cystitis
- longer treatment (2-6 weeks)
- If patient has 2 or fewer recurrent infections, use patient initiated therapy
- If patient has 3 or more and they are related to sex, use intercourse prophylaxis with Bactrim, cephalexin or nitrofurantoin
- If 3 or more not related to sex, daily or 3 times a week prophylaxis with
- Bactrim, cephalexin or nitrofurantoin
Catheter-related UTI
- About 5% of patients with catheter will develop a UTI per day (by day 30, up to 95% will have UTI).
- Only treat symptomatic patients.
- Usually caused by E.coli, candida, enterococcus, Pseudomonas, K. pneumonia, enterbacter
- Treat for 7 days if symptoms resolve promptly, 14 days if not
Prostatitis and epididymitis
- Usually gram 1 organisms
- Treat for 4 weeks
- For chronic bacterial prostatitis, give therapy for 1-4 months with Bactrim or a fluoroquinolone
- Epididymitis
  - If older than 35, probably caused by enteric organisms. Treat for 10 days to 4 weeks.
  - If younger than 35, probably gonococcal or chlamydial. Treat with ceftriaxone 250 mg times one and doxycycline BID for 10 days.
Gram – bacteremia due to UTI
- Most are uncomplicated BSI if source control is achieved.

ESBL Risk Factors:

Previous exposure to antibiotics (especially cephalosporins) is the largest risk
Previous hospitalization
UTI history/Recurrent UTIs
Congenital urological abnormalities
One study found swimming in freshwater was a risks.
These are especially important in patients with urosepsis. You likely want to empirically start a carbapenem.

Urosepsis:

You usually DO get a positive culture in sepsis from urinary pathogens. That’s good. You can treat according to susceptibilities.

The most common pathogen causing urinary tract infections (UTIs), and in turn urosepsis, is Escherichia coli (50%), followed by Proteus (15%), Enterobacter (15%), Klebsiella (15%), Pseudomonas aeruginosa (5%), and gram-positive bacteria (15% – enterococci or Staph. saprophyticus )
Urinalysis
- Urosepsis is nearly always accompanied by pyuria. Absence of pyuria largely excludes urosepsis (unless the patient is neutropenic or an obstruction is present).
Initial fluid resuscitation with crystalloid is still recommended at a minimum of 30 mL/kg. Consider early administration of vasopressor support to maintain a mean arterial pressure greater than 65 mm Hg. The first choice for vasopressor support in sepsis is norepinephrine (with epinephrine and vasopressin 2 and 3).
Possible Causes:
- Cystitis (usually not)
- Pyelonephritis
- Urinary obstruction (usually a stone).
- Emphysematous pyelonephritis (necrotizing pyelonephritis)
- Diverticulitis
- Acute bacterial prostatitis
- Prostatic abscess
- Renal abscess
- Urolithiasis
It’s important to get imaging and a good diagnosis. Antibiotics alone won’t usually fix obstructions or abscesses. You need source control and/or stent placement.
Treatment:
- You typically only need 1 antibiotic for urosepsis, but there are conflicting sources on which antibiotic you need. You will usually get a culture result, so reassess in 48-72 hours when that comes back.
- The IDSA is going to release “complicated urinary tract infection” guidelines to address this in 2024. For now:
  - Zosyn: Lower rate of causing C. difficile than other broad-spectrum antibiotics, but its not great for ESBLs (can be active).
  - Meropenem: Excellent coverage for AmpC enterobacteriaceae as well as ESBL gram-negatives. Can be good for hospital acquired urosepsis, or if suspected ESBL, but it has a high rate of C. difficile.
  - Cefepime: No ESBL coverage, but it does cover AmpC enterobacteriaceae. Misses all enterococci species. Enterococci is intrinsically resistant to all cephalosporins.
  - Ceftriaxone: Has no enterococcal coverage, no ESBL or AmpC coverage, and overuse has started to reduce the sensitivity of E. coli in many areas. In addition, it has poor urinary concentrations (it’s cleared by the liver). It’s not ideal for the sickest patients, but it’s usable if not in septic shock.
  - Aminoglycosides: Nephrotoxic, hard to dose. Can be used in combination therapy.
  - Fluoroquinolones – E. coli resistance to fluoroquinolones is growing and fluoroquinolones induce the emergence of multi-drug resistant bacteria more than most antibiotics. They also have a high rate of C. difficile.
  - Treat for 7-14 days (lots of evidence for 7 day treatment).
- Gram + Cultures:
  - If cultures are gram-negative, most of the above will work but if gram + cultures come back and the patient is deteriorating and/or on an antibiotic without enterococci coverage (like ceftriaxone or cefepime – enterococci is intrinsically resistant to cephalosporins), de-escalate to gram + coverage:
    - Vancomycin for patients at low risk of VRE (vancomycin-resistant enterococci).
    - Linezolid or daptomycin for patient with VRE risks. A single dose of daptomycin provides coverage for 24 hours (GFR >30) or 48 hours (GFR <30), then you should have cultures/sensitives.
  - Most patients will have Enterococcus faecalis and can be narrowed to ampicillin