UTI & Pyelonephritis
A Step 2 CK–focused review of UTI and pyelonephritis: ascending E. coli pathophysiology, urine dipstick and WBC-cast interpretation, cystitis vs pyelonephritis, and next-best-step antibiotic management—including the pregnancy and asymptomatic-bacteriuria treatment rules boards love to test.
Pathophysiology & Overview
UTIs are classified by site: lower tract (cystitis — bladder/urethra) and upper tract (pyelonephritis — renal pelvis and parenchyma). Nearly all are ascending infections from fecal/perineal flora that colonize the urethra and periurethral tissue. Uropathogenic *E. coli* causes ~75–90% of uncomplicated cases, adhering via P-fimbriae.
Risk factors: female sex (short urethra), sexual activity, spermicide/diaphragm use, pregnancy, urinary obstruction (stones, BPH), indwelling catheters, diabetes, and vesicoureteral reflux (recurrent childhood UTI).
A complicated UTI is infection in a structurally or functionally abnormal tract or high-risk host — male sex, pregnancy, catheter, obstruction, immunosuppression, poorly controlled diabetes, or recent instrumentation. This distinction drives the work-up (culture always; consider imaging) and lengthens antibiotic duration.
- Cystitis: dysuria, frequency, urgency, suprapubic pain — no fever
- Pyelonephritis: fever, flank/CVA tenderness, nausea/vomiting ± cystitis symptoms
- Leukocyte esterase (+) = pyuria; nitrites (+) = nitrate-reducing Enterobacterales (E. coli, Klebsiella, Proteus)
- Nitrite-negative despite true infection: Enterococcus, Staph saprophyticus, Pseudomonas → a negative nitrite does not rule out UTI
- WBC casts = upper-tract origin → pyelonephritis (highly specific)
- Urine culture is the gold standard but is not needed for uncomplicated cystitis
- Sterile pyuria (pyuria + negative routine culture) → think Chlamydia/gonorrhea urethritis, TB, or interstitial cystitis
- Order imaging (CT abd/pelvis) only if complicated, septic, or no improvement by 48–72 h
Cystitis vs Pyelonephritis vs Asymptomatic Bacteriuria
| Feature | Cystitis (lower) | Pyelonephritis (upper) | Asymptomatic bacteriuria |
|---|---|---|---|
| Symptoms | Dysuria, frequency, suprapubic pain | Fever, flank pain, CVA tenderness, N/V | None |
| Systemic signs | Absent | Present | Absent |
| WBC casts | Absent | Present | Absent |
| Work-up | Culture not routine | Urine + blood cultures | Culture (+) by definition |
| First-line Rx | Nitrofurantoin, TMP-SMX, fosfomycin | FQ or ceftriaxone; admit if septic/pregnant | Treat only if pregnant or pre-urologic procedure |
Organism → Classic Vignette Clue
| Organism | Buzzword / clue |
|---|---|
| *E. coli* | #1 overall; leukocyte esterase & nitrite positive |
| Staph saprophyticus | #2 in young, sexually active women; nitrite negative, urease (+) |
| Proteus mirabilis | Alkaline urine, urease (+), struvite staghorn stones, "fishy" ammonia smell |
| Klebsiella | Also urease (+); diabetics, hospitalized |
| Pseudomonas | Catheter, hospital, recent instrumentation; multidrug-resistant |
| Enterococcus | Elderly men, instrumentation; nitrite negative |
| Candida | Catheter, diabetes, broad-spectrum antibiotics; often colonization |
A healthy 24-year-old woman reports 2 days of dysuria, urinary frequency, and urgency. She is afebrile with mild suprapubic tenderness and no flank pain. Urine dipstick: leukocyte esterase and nitrites positive.
- Diagnosis: acute uncomplicated cystitis.
- Next best step: start empiric nitrofurantoin ×5 days. Alternatives: TMP-SMX DS ×3 days (only if local E. coli resistance <20% and no recent use) or single-dose fosfomycin.
- Urine culture is not required in uncomplicated cystitis.
- Reserve fluoroquinolones — not first-line for simple cystitis given collateral resistance and adverse effects (tendinopathy, QT, CNS).
A 32-year-old woman has 1 day of fever to 39 °C, rigors, right flank pain, nausea, and vomiting. Exam shows right CVA tenderness. UA: pyuria, positive nitrites, and WBC casts.
- Diagnosis: acute pyelonephritis.
- Next best step: obtain urine and blood cultures, then begin empiric antibiotics.
- Outpatient (mild, tolerating PO): oral fluoroquinolone (± one initial IV ceftriaxone or aminoglycoside dose).
- Inpatient (vomiting, sepsis, pregnant): IV ceftriaxone or IV fluoroquinolone.
- No improvement by 48–72 h → CT abdomen/pelvis to exclude obstruction or perinephric/renal abscess (obstructed, infected system needs urgent drainage).
- Urease-positive stone formers → struvite staghorn calculi: Proteus (classic), Klebsiella, Staph saprophyticus, Ureaplasma. Urease splits urea → ammonia → alkaline (high-pH) urine → magnesium-ammonium-phosphate (struvite) stones. (Broader urease-positive mnemonic: "Pee CHUNKSS.")
- Nitrite-negative uropathogens (cannot reduce nitrate, so a negative dipstick nitrite does not exclude UTI): Staph saprophyticus, Enterococcus, Pseudomonas, Candida.
- Epidemiology to lock in: *E. coli* is #1 for both cystitis and pyelonephritis; Staph saprophyticus is the classic #2 in young, sexually active women.
- Uncomplicated cystitis: nitrofurantoin ×5 d, TMP-SMX DS ×3 d, or single-dose fosfomycin
- Pyelonephritis: oral fluoroquinolone (outpatient) or IV ceftriaxone (inpatient); total duration ~5–14 d depending on agent
- Asymptomatic bacteriuria — treat ONLY in: (1) pregnancy, (2) before a urologic procedure with expected mucosal trauma. Do not treat elderly, diabetics, or chronically catheterized patients.
- Pregnancy: screen & treat asymptomatic bacteriuria (prevents pyelonephritis and preterm birth). Preferred/safe: amoxicillin-clavulanate, cephalexin, fosfomycin, nitrofurantoin (avoid at term). Avoid: fluoroquinolones (fetal cartilage) and TMP-SMX (1st-trimester antifolate → neural-tube defects; near-term → kernicterus).
- Emphysematous pyelonephritis: gas-forming infection almost always in diabetics (E. coli, Klebsiella); CT shows gas in the parenchyma → IV antibiotics + drainage (nephrectomy if refractory).
- Papillary necrosis associations: sickle cell disease, diabetes, analgesic overuse, obstruction, acute pyelonephritis.
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