What antibiotic can be given for a urinary tract infection (UTI) in a patient with a penicillin (PCN) allergy?

Antibiotic Options for UTI in Patients with Penicillin Allergy

For patients with penicillin allergy and UTI, fluoroquinolones (ciprofloxacin or levofloxacin) are the preferred first-line agents, with trimethoprim-sulfamethoxazole, nitrofurantoin, and aminoglycosides as alternative options depending on infection severity and local resistance patterns. 1, 2

First-Line Treatment Options by Clinical Scenario

Uncomplicated Cystitis (Oral Therapy)

• Fluoroquinolones are highly effective with no cross-reactivity to penicillins: 2, 3
  • Ciprofloxacin 500-750 mg twice daily for 7 days 1
  • Levofloxacin 750 mg once daily for 5 days 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days (if local resistance <10%) 1
• Nitrofurantoin has no cross-reactivity with penicillins and is appropriate for uncomplicated lower UTI 2, 4

Uncomplicated Pyelonephritis (Oral Therapy)

• Ciprofloxacin 500-750 mg twice daily for 7 days 1
• Levofloxacin 750 mg once daily for 5 days 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days (only if fluoroquinolone resistance <10%) 1

Complicated UTI or Pyelonephritis Requiring Hospitalization

• Fluoroquinolones (intravenous initially): 1
  • Ciprofloxacin 400 mg IV twice daily 1
  • Levofloxacin 750 mg IV once daily 1
• Aminoglycosides are safe alternatives with no cross-reactivity: 1, 2, 3
  • Gentamicin 5 mg/kg IV once daily 1, 5
  • Amikacin 15 mg/kg IV once daily 1
• Aztreonam (monobactam) has no cross-reactivity with penicillins and can be used without prior allergy testing 1, 2

Beta-Lactam Options for Penicillin-Allergic Patients

When Beta-Lactams Are Necessary

While non-beta-lactam options are preferred, certain cephalosporins can be safely used in penicillin-allergic patients with appropriate precautions:

• Cephalosporins with dissimilar side chains (such as cefazolin) can be used regardless of severity and time since reaction, as cross-reactivity is primarily related to R1 side chain similarity, not the shared beta-lactam ring 1, 2
• Ceftriaxone 1-2 g IV once daily or cefotaxime 2 g IV three times daily for complicated pyelonephritis 1
• Avoid cephalosporins with similar side chains (cephalexin, cefaclor, cefamandole) due to cross-reactivity rates of 12.9%, 14.5%, and 5.3% respectively 2
• Carbapenems can be used without prior testing in both immediate and non-severe delayed-type penicillin allergies 1, 2

Important Caveats About Cephalosporin Use

• The incidence of adverse reactions to cephalosporins in patients with penicillin allergy is low, but consideration of an alternative agent is recommended in cases of significant penicillin allergy 1
• For patients with immediate-type penicillin allergies that occurred ≤5 years ago, all penicillins should be avoided 2
• For non-severe reactions that occurred >5 years ago, other penicillins can be used in a controlled setting 2

Special Considerations for Resistant Organisms

Risk Factors for Multidrug-Resistant Pathogens

When patients have risk factors for resistant organisms, empiric therapy selection must be adjusted: 6

• Residence in nursing homes 6
• Male gender 6
• Hospitalization within the last 30 days 6
• Renal transplantation 6
• Antibiotic treatment within the last 30 days 6
• Indwelling urinary catheter 6
• Recurrent UTI 6

Antibiotic Selection Based on Risk Factors

• No risk factors: Fluoroquinolones maintain 90% susceptibility, gentamicin 95% susceptibility 6
• One risk factor: Fluoroquinolones drop to 80% susceptibility, gentamicin maintains 88% susceptibility 6
• Two or more risk factors: Fluoroquinolones drop to 52% susceptibility; gentamicin maintains 75% susceptibility 6

Alternatives for Serious Complicated UTI with Resistant Organisms

• Carbapenems (imipenem/cilastatin 0.5 g IV three times daily or meropenem 1 g IV three times daily) should be considered only in patients with early culture results indicating multidrug-resistant organisms 1
• Novel broad-spectrum agents such as ceftolozane/tazobactam 1.5 g IV three times daily or ceftazidime/avibactam 2.5 g IV three times daily 1

Common Pitfalls to Avoid

• Do not use fluoroquinolones as first-line for serious complicated UTI when patients have risk factors for resistant organisms or recent fluoroquinolone use, as resistance to first-line agents including fluoroquinolones has become increasingly common in E. coli 7
• Nitrofurantoin and fosfomycin have limited utility in complicated UTI and should be reserved as alternative treatment options for lower UTI only 7
• Avoid assuming all cephalosporins are contraindicated in penicillin allergy—cross-reactivity between penicillins and second- or third-generation cephalosporins (excluding cefamandole) is probably no higher than cross-reactivity between penicillins and other classes of antibiotics 8
• Consider local resistance patterns when selecting empiric therapy, as susceptibility towards antimicrobials depends heavily on local epidemiology 1, 6