What are the typical causes and treatments for cystitis vs pyelonephritis?

Cystitis vs Pyelonephritis: Causes and Treatment

Causative Organisms

Both cystitis and pyelonephritis are predominantly caused by Escherichia coli (75-95%), with occasional involvement of other Enterobacteriaceae such as Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus. 1

• The microbial spectrum is essentially identical for both conditions, with E. coli being the overwhelming pathogen in uncomplicated urinary tract infections 1
• Other gram-negative and gram-positive species are rarely isolated in uncomplicated UTIs 1
• Gas-forming organisms (E. coli and Klebsiella species) can cause emphysematous cystitis, a severe variant requiring urgent treatment 2

Clinical Distinction

Cystitis is a superficial bladder mucosal infection presenting with dysuria, frequency, and urgency without fever, while pyelonephritis involves tissue invasion of the upper urinary tract presenting with fever, flank pain, costovertebral angle tenderness, and systemic symptoms. 1, 3, 4

• Cystitis typically presents with lower abdominal pain, dysuria, and urinary urgency or frequency without systemic symptoms 4
• Pyelonephritis presents with high fever, malaise, vomiting, abdominal or flank pain, and tenderness 1
• Approximately one-third of acute cystitis episodes may have silent upper tract involvement despite presenting as lower UTI 3
• Pyuria is usually present with UTI regardless of location, and its absence suggests another condition 5

Treatment Approach for Cystitis

For uncomplicated acute cystitis, nitrofurantoin for 5 days or trimethoprim-sulfamethoxazole for 3 days (if local resistance <20%) are first-line treatments, with fosfomycin single-dose as an alternative. 1, 4

First-Line Options:

• Nitrofurantoin: Preferred from a public health perspective due to minimal collateral damage and lack of cross-resistance with commonly prescribed antimicrobials 1
• Trimethoprim-sulfamethoxazole (TMP-SMX): 3-day regimens are more effective than single-dose for all antimicrobials tested, but should only be used if local resistance rates are <20% 1, 4
• Fosfomycin trometamol: 3g single dose is appropriate due to minimal resistance, though may have inferior efficacy compared to standard short-course regimens 1

Alternative Options:

• Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin): Highly efficacious in 3-day regimens but should be reserved for important uses other than acute cystitis due to collateral damage concerns 1
• Beta-lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil): 3-7 day regimens are appropriate only when other recommended agents cannot be used, as they have inferior efficacy and more adverse effects 1
• Amoxicillin or ampicillin should NOT be used for empirical treatment due to poor efficacy and very high worldwide resistance prevalence 1

Treatment Approach for Pyelonephritis

For uncomplicated pyelonephritis in outpatients, oral ciprofloxacin 500mg twice daily for 7 days (or levofloxacin 750mg daily for 5 days) is first-line when local fluoroquinolone resistance is <10%, with mandatory urine culture and susceptibility testing. 1

Outpatient Management:

Always obtain urine culture and susceptibility testing before initiating therapy, then tailor treatment based on results. 1

• Fluoroquinolones (if local resistance <10%):

  • Ciprofloxacin 500mg twice daily for 7 days, with or without initial 400mg IV dose 1
  • Ciprofloxacin extended-release 1000mg daily for 7 days 1
  • Levofloxacin 750mg daily for 5 days 1

• If fluoroquinolone resistance >10%: Give initial one-time IV dose of long-acting antimicrobial (1g ceftriaxone or consolidated 24-hour aminoglycoside dose) before starting oral therapy 1

• TMP-SMX: 160/800mg (double-strength) twice daily for 14 days is appropriate ONLY if the uropathogen is known to be susceptible 1

  • If using TMP-SMX empirically when susceptibility unknown, give initial IV dose of ceftriaxone or aminoglycoside 1

• Beta-lactams: Less effective than other agents for pyelonephritis; if used, give initial IV dose of ceftriaxone or aminoglycoside, and treat for 10-14 days 1

Inpatient Management:

Women requiring hospitalization should receive IV therapy with fluoroquinolone, aminoglycoside (with or without ampicillin), extended-spectrum cephalosporin or penicillin (with or without aminoglycoside), or carbapenem, based on local resistance data. 1, 2

Critical Considerations

Resistance Patterns:

• Resistance rates vary considerably by geographic region, with generally >20% resistance to ampicillin and TMP-SMX in many areas 1
• Fluoroquinolone resistance remains <10% in most North American and European regions but is increasing 1
• Local antimicrobial susceptibility patterns of E. coli should guide empirical selection 1

Risk of Progression:

• Approximately 1% of women with cystitis develop pyelonephritis within 30 days, with 78.2% of these cases occurring in women who did not receive antibiotics 6
• Antibiotic treatment reduces pyelonephritis risk (OR 0.85 for outpatient, OR 0.65 for hospitalization), though absolute risk reduction is low 6
• Pyelonephritis can cause renal scarring leading to hypertension and chronic renal failure, though long-term risk is lower than previously thought 1

Common Pitfalls:

• Avoid diagnosing cystitis in patients with asymptomatic bacteriuria (positive culture without symptoms), as this leads to unnecessary antibiotic therapy 4
• Do not use nitrofurantoin for pyelonephritis due to inadequate tissue levels 7
• Do not use ampicillin/amoxicillin empirically due to high worldwide resistance rates 1, 2