What alternative antibiotics can be prescribed for a complicated urinary tract infection (UTI) with multiple antibiotic resistances?

Alternative Antibiotics for Complicated UTI with Multiple Resistance

For complicated UTIs with multidrug-resistant organisms, carbapenems (meropenem-vaborbactam 2g IV q8h, imipenem-cilastatin-relebactam 1.25g IV q6h) or novel β-lactam/β-lactamase inhibitor combinations (ceftazidime-avibactam 2.5g IV q8h, ceftolozane-tazobactam 1.5g IV q8h, cefiderocol 2g IV q8h) should be prescribed based on culture results and local resistance patterns. 1

Immediate Empiric Parenteral Options

First-Line Carbapenem-Based Regimens

• Meropenem-vaborbactam 2g IV every 8 hours is recommended for carbapenem-resistant Enterobacteriaceae (CRE), with evidence showing superiority over best available therapy in the TANGO-II trial 1
• Imipenem-cilastatin-relebactam 1.25g IV every 6 hours provides coverage against KPC-producing CRE and carbapenem-resistant Pseudomonas aeruginosa, demonstrated in the RESTORE-IMI-1 trial 1
• Standard meropenem 1g IV every 8 hours or imipenem-cilastatin 0.5g IV every 8 hours remain options when early culture results confirm multidrug resistance 1, 2

Novel β-Lactam/β-Lactamase Inhibitor Combinations

• Ceftazidime-avibactam 2.5g IV every 8 hours is highly effective for CRE infections, particularly KPC-producing organisms 1, 3
• Ceftolozane-tazobactam 1.5g IV every 8 hours provides excellent coverage for multidrug-resistant Pseudomonas aeruginosa 1, 4
• Cefiderocol 2g IV every 8 hours is a siderophore cephalosporin active against carbapenem-resistant organisms including metallo-β-lactamase producers 1, 4

Aminoglycoside Options

For Severe Infections

• Plazomicin 15 mg/kg IV every 12 hours is specifically recommended for CRE-associated complicated UTIs, with the CARE trial showing fewer deaths (24% vs 50%) and lower acute kidney injury (16.7% vs 50%) compared to colistin-based regimens 1, 5, 6
• Amikacin 15 mg/kg IV once daily maintains excellent activity against many multidrug-resistant organisms, with susceptibility rates of 38.2% even against CRE in surveillance studies 1
• Gentamicin 5 mg/kg IV once daily can be used, though not studied as monotherapy in complicated UTI 1

For Simple Cystitis with Resistance

• Single-dose aminoglycoside (amikacin or gentamicin) is recommended for patients with simple cystitis due to CRE, as urinary concentrations exceed therapeutic levels for days after a single dose 1

Alternative Agents for Specific Resistance Patterns

For ESBL-Producing Organisms

• Piperacillin-tazobactam 4.5g IV every 6-8 hours can be used for ESBL-producing E. coli in mild-moderate UTIs based on susceptibility testing 1, 3, 4
• Cefepime 2g IV every 12 hours remains active against some ESBL producers and AmpC-producing organisms 1, 3

For Carbapenem-Resistant Organisms

• Fosfomycin IV displays good in vitro activity against CRE and is recommended by ESCMID guidelines for complicated UTI without septic shock 1
• Colistin should be reserved as a last-resort option due to toxicity concerns 1, 3, 4

Critical Management Principles

Culture-Directed Therapy is Mandatory

• Obtain urine culture before initiating antibiotics to guide targeted therapy, as the microbial spectrum in complicated UTIs includes E. coli, Proteus spp., Klebsiella spp., Pseudomonas spp., Serratia spp., and Enterococcus spp. 1, 5
• Adjust therapy based on culture results and susceptibility patterns within 48-72 hours 1, 5

Treatment Duration

• Treat for 7-14 days total, with 14 days recommended for males when prostatitis cannot be excluded 1, 5
• Consider 7-day duration when patient is hemodynamically stable and afebrile for at least 48 hours 5

Address Underlying Factors

• Manage urological abnormalities (obstruction, foreign bodies, incomplete voiding) as optimal antimicrobial therapy alone is insufficient without source control 1, 5

Common Pitfalls to Avoid

• Do not use fluoroquinolones empirically if local resistance exceeds 10% or if the patient received fluoroquinolones in the last 6 months 1, 7
• Avoid carbapenems as first-line empiric therapy unless early culture results indicate multidrug-resistant organisms, to preserve their effectiveness 1
• Monitor renal function closely with aminoglycosides, as nephrotoxicity risk increases with high serum concentrations, prolonged therapy, and concurrent nephrotoxic drugs 8
• Do not rely on oral agents alone for severe complicated UTIs with multidrug resistance—parenteral therapy is essential initially 1, 5