Urinary Tract Infections

Organisms grouped by mechanism

• Enteric gram-negative rods (fecal-perineal-urethral ascent): E. coli causes the large majority of both community-acquired cystitis and pyelonephritis; Klebsiella pneumoniae, Proteus, Enterobacter, and Serratia follow. All are nitrate-reducers, so dipstick nitrites are typically positive.
• Urease producers (stone-associated): Proteus mirabilis, Klebsiella, and Morganella split urea into ammonia, alkalinizing urine and precipitating struvite (magnesium ammonium phosphate) staghorn calculi — a nidus for relapsing infection that antibiotics alone cannot clear.
• Gram-positive uropathogens: Staphylococcus saprophyticus (coagulase-negative, novobiocin-resistant) in young sexually active women — classically nitrite-negative; Enterococcus and group B Streptococcus in instrumented, catheterized, or pregnant patients.
• Healthcare-associated/biofilm organisms: Pseudomonas aeruginosa, Candida, and multidrug-resistant Enterobacterales in patients with indwelling catheters, stents, or repeated antibiotic exposure.
• Non-bacterial mimic: adenovirus hemorrhagic cystitis in children and transplant recipients — gross hematuria with sterile culture.

Modifiable risk factors

• Sexual intercourse and spermicide/diaphragm use: mechanical inoculation plus spermicide-induced loss of protective vaginal lactobacilli.
• Indwelling urinary catheters: risk rises with each catheter-day; the IDSA catheter-associated UTI guidance emphasizes avoiding unnecessary catheters and early removal.
• Urinary stasis and incomplete emptying: neurogenic bladder, constipation, poorly controlled diabetes with autonomic neuropathy.
• Instrumentation/urologic surgery and prior antibiotic exposure (selects resistant flora).

Non-modifiable risk factors

• Female anatomy: short urethra and perineal proximity to rectal flora.
• Obstruction: BPH, stricture, stones, malignancy, or pregnancy-related ureteral compression with progesterone-mediated smooth muscle relaxation.
• Vesicoureteral reflux and congenital anomalies in children.
• Postmenopausal estrogen deficiency (vaginal atrophy, loss of lactobacilli) — the AUA recurrent UTI guideline supports vaginal estrogen as prophylaxis.
• Host genetics: non-secretor blood group phenotype and P blood group antigen expression favor P-fimbriated E. coli adherence; prior UTI is the strongest predictor of the next one.

• Bacterial adherence and colonization: Uropathogenic E. coli (UPEC) express P fimbriae (pili) that bind to α-D-galactosyl receptors on uroepithelial cells; this adherence is the critical first step in pathogenesis and prevents bacterial washout during micturition
• Ascending infection and tissue invasion: Bacteria ascend the urethra and colonize the bladder; virulence factors include hemolysin and aerobactin (iron acquisition), which facilitate invasion through the urothelium and trigger inflammatory responses
• Host defense mechanisms and their breakdown: The urothelial barrier (glycosaminoglycan layer and tight junctions), urine osmolality and pH, neutrophil infiltration, and normal microbial flora normally prevent infection; compromise of any component (urinary stasis, obstruction, instrumentation, urinary catheterization, pregnancy-related anatomical changes) increases UTI risk
• Biofilm formation: In chronic or recurrent UTIs and especially with indwelling catheters, bacteria form biofilms that are resistant to antibiotics and host immune responses, leading to persistent infection
• Pyelonephritis mechanism: Bacterial ascent to the kidneys via the ureters causes tubular damage, interstitial inflammation, and potential renal scarring, especially in children; vesicoureteral reflux (VUR) facilitates this process

Acute Cystitis (Lower UTI)

• Dysuria (burning on urination) — the hallmark symptom
• Urinary frequency and urgency — can present suddenly and severely
• Suprapubic pain or discomfort — typically mild to moderate; tenderness on abdominal exam
• Hematuria (gross or microscopic) — common but nonspecific; indicates mucosal irritation
• Absence of systemic symptoms — fever is NOT typical of uncomplicated cystitis; its presence suggests upper UTI or complicated infection

Acute Pyelonephritis (Upper UTI)

• High fever (often >39°C) — cardinal finding distinguishing upper from lower UTI
• Flank pain and costovertebral angle (CVA) tenderness — classic presentation
• Nausea and vomiting — often prominent
• Dysuria and frequency may still be present — overlapping symptoms with cystitis
• Possible sepsis features — tachycardia, tachypnea, hypotension in severe cases

Asymptomatic Bacteriuria

• No urinary symptoms despite positive culture (≥10⁵ CFU/mL in two consecutive specimens in women, single specimen in men)
• Screening recommended in pregnant women and those undergoing urologic procedures; NOT recommended in non-pregnant women or diabetic women (exception: pregnancy)

Important Clinical Pearls

• Suprapubic pain without fever = cystitis; flank pain WITH fever = pyelonephritis
• In elderly patients, UTI may present atypically with delirium, confusion, or falls without classic urinary symptoms
• Catheterized patients may present with fever alone; standard urinary symptoms unreliable in this population
• Men with UTI should raise suspicion for anatomic abnormality or complication (prostatitis, urinary obstruction); empiric treatment differs from women

• Urinalysis (UA) with microscopy: Look for pyuria (≥5 WBCs/hpf), bacteriuria (bacteria visible), and nitrites (produced by gram-negative bacteria, especially E. coli; highly specific but insensitive); leukocyte esterase (released by neutrophils, sensitive but not specific); RBCs suggest hematuria but are nonspecific; WBC casts suggest pyelonephritis if present
• Urine culture: Gold standard for diagnosis; obtain before antibiotics if possible; defines organism and susceptibility; threshold for diagnosis is ≥10⁵ CFU/mL (100,000/mL) in symptomatic women with two consecutive midstream clean-catch specimens, ≥10² CFU/mL (100/mL) in symptomatic women with straight catheterization, and ≥10³ CFU/mL (1,000/mL) in men (single specimen); in asymptomatic bacteriuria, two positive cultures required
• Dipstick testing: Convenient point-of-care test; nitrites and leukocyte esterase suggest UTI but negative test does NOT exclude infection (absent in gram-positive cocci like S. saprophyticus and some Klebsiella species); hematuria nonspecific
• Blood cultures: Obtain in hospitalized patients or those with urosepsis/pyelonephritis to guide therapy and identify bacteremia
• Imaging considerations: Renal ultrasound or CT indicated for complicated UTIs (obstruction, abscess, xanthogranulomatous pyelonephritis); VCUG (voiding cystourethrogram) in children with pyelonephritis to exclude VUR; imaging NOT routinely needed for uncomplicated cystitis in women
• Post-void residual (PVR): Check if retention suspected; PVR >100 mL suggests incomplete emptying and UTI risk

Uncomplicated Cystitis in Non-Pregnant Women

• First-line: Nitrofurantoin 100 mg PO BID × 5-7 days (excellent for lower UTI; concentrates in urine; avoid near term pregnancy and in G6PD deficiency)
• Alternative first-line options:
• Trimethoprim-sulfamethoxazole (TMP-SMX) DS 160/800 mg PO BID × 3 days if local resistance <20%; shorter duration effective for uncomplicated cystitis
• Fosfomycin 3 g PO single dose — single-dose advantage, good option if resistance concerns; pregnancy-safe
• Fluoroquinolone (e.g., ciprofloxacin 250 mg BID × 3 days) — reserved for allergy or resistance due to side effects (tendinopathy, QT prolongation, C. difficile risk)
• Avoid: Long-acting fluoroquinolones and aminoglycosides for uncomplicated cystitis (overkill)

Acute Pyelonephritis (Outpatient)

• Mild-moderate disease: Fluoroquinolone (e.g., ciprofloxacin 500 mg PO BID or levofloxacin 750 mg daily × 5-7 days) OR amoxicillin-clavulanate (if susceptibility known and organism suitable); ensure clinical improvement in 48-72 hours
• Able to tolerate PO, no vomiting: Can initiate outpatient oral therapy with close follow-up

Acute Pyelonephritis (Hospitalized/Severe)

• IV fluoroquinolone: Levofloxacin 750 mg IV daily or ciprofloxacin 400 mg IV q8-12h
• IV cephalosporin: Ceftriaxone 1-2 g IV daily or cefepime 1-2 g IV q8-12h (especially for E. coli; excellent coverage)
• IV aminoglycoside + ampicillin: Gentamicin 5-7 mg/kg IV daily + ampicillin 1 g IV q6h (for enterococci coverage if risk factors)
• **De-escalate to

Complications of the infection

• Urosepsis/septic shock — emergency: bacteremic seeding from an inflamed pyelonephritic kidney; signals are fever with hypotension, tachypnea, lactate elevation, and altered mentation. Requires blood and urine cultures, early broad-spectrum IV antibiotics, and fluid resuscitation.
• Obstructive pyonephrosis — emergency: pus under pressure behind a stone or stricture. Suspect when fever persists beyond 48–72 hours of appropriate antibiotics; CT shows hydronephrosis. Antibiotics alone fail — source control by ureteral stent or percutaneous nephrostomy is the definitive step.
• Renal or perinephric abscess: persistent fever with a focal fluid collection on CT; needs drainage plus prolonged antibiotics.
• Emphysematous pyelonephritis — emergency: necrotizing infection by gas-forming organisms (E. coli, Klebsiella) almost exclusively in poorly controlled diabetes; gas within the renal parenchyma on CT is the finding.
• Papillary necrosis: ischemic sloughing of medullary papillae in diabetes, sickle cell disease, analgesic nephropathy, or obstruction — flank pain with sloughed tissue in urine and gross hematuria.
• Xanthogranulomatous pyelonephritis: chronic *Proteus*/staghorn-associated destruction with lipid-laden macrophages and a "bear paw" nephrogram; treated with nephrectomy.
• Reflux nephropathy: recurrent childhood pyelonephritis with VUR causes cortical scarring → hypertension and CKD. The AAP recommends renal-bladder ultrasound after a first febrile UTI in infants 2–24 months.
• Pregnancy: pyelonephritis precipitates preterm labor and can cause ARDS — admit for IV therapy.

Complications of treatment

• Nitrofurantoin: hemolysis in G6PD deficiency, acute pneumonitis and chronic pulmonary fibrosis, peripheral neuropathy when renal clearance is reduced; it fails in pyelonephritis because it does not reach renal parenchymal levels.
• TMP-SMX: hyperkalemia (epithelial sodium channel blockade), a benign creatinine rise from blocked tubular secretion, hypersensitivity/*Stevens-Johnson syndrome*, and fetal risk (neural tube defects early, kernicterus near term).
• Fluoroquinolones: FDA boxed warnings for tendinopathy/rupture, peripheral neuropathy, CNS effects, and aortic aneurysm/dissection; also QT prolongation.
• Aminoglycosides: acute tubular necrosis and irreversible ototoxicity.
• Any agent: Clostridioides difficile colitis and selection of ESBL-producing organisms requiring carbapenems.

• Nitrite-negative, leukocyte esterase-positive UTI in a young sexually active woman: think Staphylococcus saprophyticus — coagulase-negative and novobiocin-resistant (S. epidermidis is novobiocin-sensitive). It cannot reduce nitrate, which is why the dipstick nitrite is negative.
• Alkaline urine + staghorn calculus + recurrent UTI: Proteus mirabilis urease. The stone is struvite, and the answer is stone removal plus antibiotics, not antibiotics alone.
• Pregnancy is the exception to "don't treat asymptomatic bacteriuria." USPSTF recommends screening pregnant patients with urine culture, and IDSA 2019 endorses treatment, because untreated bacteriuria progresses to pyelonephritis and preterm birth. Do not treat asymptomatic bacteriuria in non-pregnant women, diabetics, elderly nursing-home residents, or catheterized patients — the single most common distractor on this topic.
• Nitrofurantoin is a bladder drug only. It concentrates in urine but not renal parenchyma, so choosing it for pyelonephritis is always wrong; also avoid it with significantly reduced creatinine clearance and near term (neonatal hemolysis).
• Fever persisting past 48–72 hours of appropriate therapy in pyelonephritis → the single best next step is CT of the abdomen/pelvis looking for abscess, obstruction, or emphysematous change, not a reflexive antibiotic change.
• Sterile pyuria (pyuria with a negative routine culture) points away from typical uropathogens: Chlamydia trachomatis urethritis, gonorrhea, genitourinary tuberculosis, or interstitial nephritis.
• A man with a UTI is a complicated UTI. Evaluate for prostatitis (boggy, tender prostate; avoid vigorous massage) or obstruction, and use an agent with prostatic penetration such as a fluoroquinolone or TMP-SMX for a longer course.
• Delirium in an elderly patient with bacteriuria is not automatically a UTI. Per IDSA 2019, look for another cause before attributing symptoms to a positive culture; and in catheterized patients, exchange or remove the catheter as part of treatment.