Can multidrug-resistant urinary tract infections (UTIs) be treated with cephalexin?

Treatment of Multidrug-Resistant UTIs: Cephalexin is Not Recommended

Cephalexin is not recommended for the treatment of multidrug-resistant urinary tract infections (MDR-UTIs) as it lacks efficacy against resistant organisms and more appropriate therapeutic options exist. 1

Understanding MDR-UTIs and Treatment Options

Definition and Scope

• MDR-UTIs are typically caused by organisms resistant to multiple antimicrobial classes, including:
  • Extended-spectrum β-lactamase (ESBL) producing Enterobacterales
  • Carbapenem-resistant Enterobacterales (CRE)
  • Multidrug-resistant Pseudomonas species
  • Vancomycin-resistant enterococci (VRE)

Recommended Treatment Approach for MDR-UTIs

For Complicated UTIs due to CRE:

1. First-line options 1:

   • Ceftazidime-avibactam 2.5g IV q8h (weak recommendation, very low quality evidence)
   • Meropenem-vaborbactam 4g IV q8h (weak recommendation, low quality evidence)
   • Imipenem-cilastatin-relebactam 1.25g IV q6h (weak recommendation, low quality evidence)

2. For non-severe infections 1:

   • Aminoglycosides (including plazomicin) for cUTIs (conditional recommendation)
   • Single-dose aminoglycoside for simple cystitis due to CRE

For UTIs due to ESBL-producing organisms:

• Carbapenems (imipenem or meropenem) are recommended for severe infections 1
• For non-severe infections: piperacillin-tazobactam, aminoglycosides, or fosfomycin 1, 2

Why Cephalexin is Not Appropriate for MDR-UTIs

1. Limited spectrum against resistant organisms:

   • First-generation cephalosporins like cephalexin lack activity against ESBL-producing organisms, CRE, and other MDR pathogens 2
   • Cephalexin is only effective against non-ESBL producing Enterobacterales 2, 3

2. Guideline recommendations:

   • Current guidelines do not include cephalexin in treatment algorithms for MDR-UTIs 1
   • For uncomplicated UTIs, cephalexin is considered only as a second-line option, not for MDR infections 2

3. Better alternatives exist:

   • For MDR-UTIs, newer agents with specific activity against resistant mechanisms are preferred 1
   • Even for uncomplicated UTIs, nitrofurantoin, fosfomycin, and pivmecillinam are preferred first-line options 4, 2

Appropriate Use of Cephalexin in UTIs

Cephalexin may be appropriate for:

• Non-MDR, uncomplicated UTIs as a second-line option 2, 3
• UTIs caused by susceptible organisms (confirmed by culture) 3, 5
• Dosing of 500mg twice daily has shown similar efficacy to four times daily dosing in non-MDR UTIs 6, 5

Clinical Approach to MDR-UTIs

1. Obtain cultures before initiating therapy 4
2. Consider infectious disease consultation (strong recommendation, low quality evidence) 1
3. Select therapy based on:
   • Severity of infection
   • Local resistance patterns
   • Previous antibiotic exposures
   • Susceptibility testing results 1

Important Caveats

• Antimicrobial susceptibility testing is essential to guide therapy for MDR-UTIs 1
• Combination therapy may be required for severe MDR-UTIs with limited treatment options 1
• Prolonged infusion of β-lactams for pathogens with high MICs is recommended 1
• Newer agents should be used judiciously to prevent further resistance development 2

In conclusion, while cephalexin has a role in treating uncomplicated UTIs caused by susceptible organisms, it is not an appropriate choice for multidrug-resistant UTIs where more targeted antimicrobial agents are required based on susceptibility testing.