What are the treatment options for a urinary tract infection (UTI) in a patient with allergies to common UTI medications?

Treatment Options for UTI with Multiple Drug Allergies

For patients with allergies to common UTI medications, fosfomycin and nitrofurantoin are the primary oral alternatives for uncomplicated lower UTIs, while aminoglycosides, newer beta-lactam/beta-lactamase inhibitor combinations, and IV fosfomycin serve as options for complicated infections.

Uncomplicated Lower UTI (Cystitis)

First-Line Oral Alternatives

• Fosfomycin 3 grams as a single oral dose is highly effective for acute uncomplicated cystitis, achieving bacteriological eradication rates of 75-90% at 5-11 days post-therapy 1
• This single-dose regimen maintains high urinary concentrations (>128 mg/L) for 24-48 hours, sufficient to inhibit most uropathogens 1
• Fosfomycin demonstrates excellent activity against E. coli and other common uropathogens, with minimal cross-resistance to other antibacterial agents 2, 1
• Nitrofurantoin 100 mg orally twice daily for 5 days represents another excellent first-line option, with clinical and microbiological cure rates of 90-92% 3
• Nitrofurantoin maintains activity against vancomycin-resistant enterococci (VRE) and demonstrates 68-92% microbiological cure rates against various resistant uropathogens 3

Critical Limitations to Avoid

• Never use nitrofurantoin for pyelonephritis or systemic infections as it does not achieve adequate serum concentrations 3
• Nitrofurantoin is contraindicated in the last trimester of pregnancy due to hemolytic anemia risk in newborns 3
• Fosfomycin should not be used beyond 2 days when combined with antibacterials, as there is no evidence of additional benefit 4

Complicated UTI (cUTI)

For Multidrug-Resistant Organisms

When dealing with carbapenem-resistant Enterobacterales (CRE) or extended-spectrum beta-lactamase (ESBL) producers:

• Ceftazidime-avibactam 2.5 g IV every 8 hours is recommended for cUTIs caused by CRE 5
• Meropenem-vaborbactam 4 g IV every 8 hours or imipenem-cilastatin-relebactam 1.25 g IV every 6 hours are FDA-approved alternatives for CRE-associated cUTI 5
• Plazomicin 15 mg/kg IV every 12 hours represents a novel aminoglycoside option stable against aminoglycoside-modifying enzymes, with lower mortality (24% vs 50%) and reduced acute renal injury (16.7% vs 50%) compared to colistin-based regimens 5

For Simple Cystitis Due to Resistant Organisms

• Single-dose aminoglycoside achieves microbiologic cure rates of 87-100% for lower UTIs, as urinary concentrations exceed peak plasma levels by 25- to 100-fold 5
• This approach is particularly useful for CRE-associated simple cystitis 5

For VRE-Associated UTI

• Fosfomycin 3 g orally as a single dose is recommended for uncomplicated UTIs due to VRE 5
• Nitrofurantoin 100 mg orally every 6 hours serves as an alternative for uncomplicated VRE UTIs 5
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg every 8 hours can be used for uncomplicated VRE UTIs 5

Complicated Upper UTI and Pyelonephritis

IV Fosfomycin for Severe Infections

• IV fosfomycin 6 grams every 8 hours for 7 days (14 days with concurrent bacteremia) demonstrated superiority over piperacillin-tazobactam in the ZEUS trial for complicated upper UTIs 6
• This regimen showed superior microbiological eradication rates across all resistant phenotypes, including ESBL-producing organisms and carbapenem-resistant Enterobacterales 6

Oral Fosfomycin for Complicated Lower UTI

• Oral fosfomycin 3 grams every 48-72 hours for 3 total doses is supported for patients with cLUTI who have failed other treatments, are infected with MDR pathogens, or cannot tolerate first-line agents 6

Treatment Duration Considerations

• 7 days is generally recommended for cUTI when the patient is hemodynamically stable and afebrile for at least 48 hours 5
• 14 days should be considered for men when prostatitis cannot be excluded 5
• Treatment duration must be closely related to management of the underlying urological abnormality 5

Essential Management Principles

• Always obtain urine culture and susceptibility testing before initiating therapy for complicated UTIs 5
• Address the underlying urological abnormality or complicating factor, as this is mandatory for successful treatment 5
• Consider local resistance patterns when selecting empirical therapy 5
• Phenazopyridine can provide symptomatic relief but should not exceed 2 days and does not replace definitive antimicrobial therapy 4