What is the appropriate treatment for Escherichia coli isolated from urine in an otherwise healthy adult woman with uncomplicated cystitis, and how does management differ for men, pregnant patients, or asymptomatic bacteriuria?

Treatment of E. coli in Urine

For an otherwise healthy, non-pregnant adult woman with uncomplicated cystitis caused by E. coli, prescribe nitrofurantoin 100 mg orally twice daily for 5 days as first-line therapy, achieving approximately 93% clinical cure with minimal resistance and collateral damage. 1

Management by Patient Population

Healthy Non-Pregnant Women with Uncomplicated Cystitis

First-line options (choose based on local resistance and patient factors):

• Nitrofurantoin 100 mg PO BID × 5 days – Preferred agent with 93% clinical cure, 88% microbiological eradication, and worldwide resistance <1%; preserves intestinal flora and minimizes C. difficile risk. 1 Contraindicated when eGFR <30 mL/min/1.73 m². 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg PO BID × 3 days – Use only when local E. coli resistance is <20% and the patient has not received TMP-SMX in the prior 3 months; provides 93% clinical cure and 94% microbiological eradication when susceptible. 1 Many regions now exceed 20% resistance, making verification of local antibiogram data mandatory. 1

• Fosfomycin 3 g single oral dose – Achieves ~91% clinical cure with therapeutic urinary concentrations for 24–48 hours; resistance rates remain low at 2.6% for initial infections. 1 Do not use for suspected pyelonephritis due to insufficient tissue penetration. 1

Reserve agents (use only for culture-proven resistance or first-line failure):

• Fluoroquinolones (ciprofloxacin 250–500 mg BID or levofloxacin 250–750 mg daily × 3 days) – Reserved for documented resistant organisms because serious adverse effects (tendon rupture, peripheral neuropathy, CNS toxicity) outweigh benefits in uncomplicated UTI. 1 Global resistance exceeds 10% in many regions. 1

• Beta-lactams (amoxicillin-clavulanate, cefdinir, cefpodoxime × 3–7 days) – Achieve only 89% clinical cure and 82% microbiological eradication, significantly inferior to first-line agents. 1 Never use amoxicillin or ampicillin alone due to 55–67% worldwide resistance. 1

Diagnostic approach:

• Routine urine culture is not required for typical uncomplicated cystitis in healthy women. 1
• Obtain culture and susceptibility testing when: symptoms persist after therapy, recurrence within 2–4 weeks, fever >38°C/flank pain/CVA tenderness, atypical presentation, or history of resistant organisms. 1

Men with UTI

All UTIs in men are considered complicated and require different management than uncomplicated cystitis in women. 2 Men require:

• Urine culture before initiating therapy 2
• Longer treatment duration (typically 7 days minimum) 2
• Investigation for underlying urologic abnormalities if recurrent 2
• Do not screen for or treat asymptomatic bacteriuria in men unless undergoing urologic procedures with mucosal bleeding. 2

Pregnant Women

Pregnancy is the one clinical scenario where even asymptomatic bacteriuria must always be treated due to 20–30 fold increased pyelonephritis risk (from 1–4% with treatment to 20–35% without). 3, 4

Screening and diagnosis:

• Screen all pregnant women with urine culture at 12–16 weeks gestation or first prenatal visit if later. 2, 3, 4
• Dipstick testing has only 50% sensitivity for bacteriuria in pregnancy; urine culture is mandatory. 3, 4
• Obtain culture before starting antibiotics in all symptomatic cases. 3, 4

First-line treatment options:

• Nitrofurantoin 50–100 mg PO QID × 7 days or 100 mg PO BID × 7 days – Preferred throughout pregnancy including first trimester; safe with no fetal toxicity in 91 pregnancies studied. 3, 4 Avoid near term due to theoretical neonatal hemolytic anemia risk. 3

• Fosfomycin 3 g single dose – Acceptable alternative for uncomplicated lower UTI with minimal resistance and low ecological damage. 3, 4

• Cephalexin 500 mg PO QID × 7–14 days – Safe alternative when nitrofurantoin contraindicated; first-generation cephalosporins have resistance rates generally <10%. 3, 4

Avoid in pregnancy:

• Trimethoprim-sulfamethoxazole – Contraindicated in first trimester (neural tube defects) and third trimester (neonatal kernicterus); may use in second trimester if susceptible. 3, 4
• Fluoroquinolones – Avoid throughout pregnancy due to fetal cartilage development concerns. 3, 4

Treatment duration:

• Asymptomatic bacteriuria: 4–7 days 2, 3
• Symptomatic cystitis: 7 days 3, 4
• Pyelonephritis: 7–14 days with initial parenteral ceftriaxone or cefepime if hospitalized 3, 4

Follow-up:

• Urine culture 1–2 weeks after treatment to confirm cure 3, 4
• Monthly screening throughout pregnancy to detect recurrence 4
• Consider prophylactic antibiotics for recurrent infections 3

Special consideration – Group B Streptococcus:

• GBS bacteriuria at any concentration during pregnancy indicates heavy genital colonization and requires treatment at diagnosis plus intrapartum prophylaxis during labor. 4 Women with GBS bacteriuria do not need vaginal-rectal screening at 35–37 weeks. 4

Asymptomatic Bacteriuria (Non-Pregnant)

Do not screen for or treat asymptomatic bacteriuria in the following populations, as treatment provides no clinical benefit and promotes resistance: 2

• Healthy premenopausal non-pregnant women 2
• Healthy postmenopausal women 2
• Diabetic patients (men or women) 2
• Elderly community-dwelling or institutionalized patients 2
• Patients with spinal cord injury 2
• Catheterized patients while catheter remains in place 2
• Renal transplant recipients >1 month post-transplant 2
• Non-renal solid organ transplant recipients 2

Exceptions – treat asymptomatic bacteriuria:

• Pregnant women (Grade A recommendation) 2
• Before transurethral resection of prostate 2
• Before other urologic procedures with anticipated mucosal bleeding 2

Critical Decision Algorithm

Step 1: Classify the infection

• Lower tract symptoms only (dysuria, frequency, urgency) without fever/flank pain = uncomplicated cystitis → short-course oral therapy (3–5 days) 1
• Fever >38°C, flank pain, or CVA tenderness = pyelonephritis → 7–14 day regimen with fluoroquinolone or parenteral cephalosporin 1
• Asymptomatic bacteriuria in non-pregnant patient = do not treat (except pre-procedure) 2

Step 2: Assess local TMP-SMX resistance

• If <20% and no TMP-SMX use in past 3 months → prescribe TMP-SMX 160/800 mg BID × 3 days 1
• If ≥20% or data unavailable → prescribe nitrofurantoin 100 mg BID × 5 days or fosfomycin 3 g single dose 1

Step 3: Monitor response

• If symptoms persist after 2–3 days or recur within 2 weeks → obtain urine culture and switch to different antibiotic class for 7-day course 1
• Reserve fluoroquinolones only for culture-proven resistance 1
• If fever persists >72 hours → obtain imaging (ultrasound or CT) to exclude obstruction or abscess 1

Common Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant, non-catheterized patients – this promotes resistance without clinical benefit. 2

• Do not use empiric fluoroquinolones as first-line therapy for uncomplicated cystitis due to serious adverse effects and rising resistance. 1

• Do not prescribe TMP-SMX without confirming local E. coli resistance is <20%; failure rates increase sharply above this threshold. 1

• Do not use nitrofurantoin when eGFR <30 mL/min/1.73 m² or for suspected pyelonephritis. 1

• Do not use oral fosfomycin for suspected upper-tract infection or pyelonephritis. 1

• Do not rely on negative dipstick to rule out UTI in pregnancy – symptoms warrant culture and empiric treatment regardless of dipstick results. 3, 4

• Pyuria accompanying asymptomatic bacteriuria is not an indication for treatment. 2