What intravenous (IV) antibiotic should I give to a patient with a complicated urinary tract infection (UTI) and impaired renal function, considering potential antibiotic resistance and severe penicillin allergy?

Recommended IV Antibiotic for Complicated UTI with Renal Impairment and Severe Penicillin Allergy

Start with IV ceftriaxone 1-2 g once daily as your first-line empiric therapy, as this extended-spectrum cephalosporin provides broad coverage against common uropathogens, requires no renal dose adjustment, and has a low cross-reactivity rate (approximately 1-3%) with penicillins in patients with severe penicillin allergy. 1, 2

Initial Assessment and Culture Collection

• Obtain urine culture with susceptibility testing before initiating antibiotics to guide targeted therapy, as complicated UTIs have a broader microbial spectrum and increased likelihood of antimicrobial resistance 1, 2
• Send blood cultures if the patient is febrile, hemodynamically unstable, or has signs of systemic infection 1
• Assess creatinine clearance as soon as possible to guide subsequent antibiotic adjustments 2

Primary Empiric IV Options Based on Allergy Severity

If Cross-Reactivity Risk is Acceptable (Non-IgE Mediated Penicillin Allergy)

Ceftriaxone 2 g IV once daily is the preferred agent because:

• No renal dose adjustment required, making it ideal when renal function is impaired or unknown 1, 2
• Excellent urinary concentrations and broad-spectrum activity against E. coli, Proteus, Klebsiella, and other common uropathogens 2
• Once-daily dosing simplifies administration 1

Alternative cephalosporin: Cefepime 2 g IV every 12 hours if you need enhanced Pseudomonas coverage, though this requires renal dose adjustment once creatinine clearance is known 1, 2

If True IgE-Mediated Severe Penicillin Allergy (Anaphylaxis, Stevens-Johnson Syndrome)

Avoid all beta-lactams entirely due to 10-15% cross-reactivity risk with cephalosporins in severe IgE-mediated reactions 2

Use levofloxacin 750 mg IV once daily as your primary alternative if:

• Local fluoroquinolone resistance is <10% 1, 2
• No recent fluoroquinolone exposure in the past 3 months 2
• Requires renal dose adjustment: reduce to 750 mg every 48 hours if CrCl <20 mL/min 2

Use aztreonam 1-2 g IV every 8 hours as a beta-lactam alternative with no cross-reactivity to penicillins if:

• Fluoroquinolones are contraindicated or resistance is suspected 1
• Gram-negative coverage is needed without penicillin cross-reactivity risk 1
• Requires renal dose adjustment once creatinine clearance is known 1

Critical Agents to AVOID in This Clinical Scenario

• Aminoglycosides (gentamicin, amikacin, plazomicin) should be avoided until creatinine clearance is calculated, as these are nephrotoxic and require precise weight-based dosing adjusted for renal function 1, 2
• Piperacillin/tazobactam is absolutely contraindicated given the severe penicillin allergy 3
• Carbapenems (meropenem, imipenem, ertapenem) should be avoided due to 1-10% cross-reactivity with penicillins in severe allergic reactions 1
• Nitrofurantoin, fosfomycin, or pivmecillinam should not be used for complicated UTIs, as these agents have insufficient tissue penetration and lack efficacy data for complicated infections 1, 2

When to Escalate to Broader Spectrum Agents

Consider ceftazidime/avibactam 2.5 g IV every 8 hours (with renal adjustment) if:

• Early culture results indicate ESBL-producing organisms 1
• Carbapenem-resistant Enterobacterales (CRE) is suspected based on prior cultures or epidemiologic risk factors 1
• Patient remains febrile after 72 hours on initial therapy 1

Consider ceftolozane/tazobactam 1.5 g IV every 8 hours (with renal adjustment) if:

• Multidrug-resistant Pseudomonas aeruginosa is suspected or confirmed 1, 2
• Patient has nosocomial UTI with risk factors for resistant organisms 1

Renal Dose Adjustments Once Creatinine Clearance is Known

For Ceftriaxone

• No adjustment needed regardless of renal function, making it the most practical choice 2

For Levofloxacin

• CrCl 20-49 mL/min: 750 mg IV once, then 750 mg every 48 hours 2
• CrCl <20 mL/min: 750 mg IV once, then 500 mg every 48 hours 2

For Cefepime

• CrCl 30-60 mL/min: 2 g every 12 hours 1
• CrCl 11-29 mL/min: 2 g every 24 hours 1
• CrCl <10 mL/min: 1 g every 24 hours 1

Treatment Duration and Oral Step-Down Strategy

• Treat for 7-14 days total, with 7 days appropriate if prompt clinical response (afebrile for 48 hours, hemodynamically stable) and 14 days if delayed response or if prostatitis cannot be excluded in males 1, 2
• Switch to oral antibiotics once clinically stable and culture results available 2

Oral Step-Down Options (Based on Susceptibility)

• Levofloxacin 750 mg PO daily for 5-7 days if susceptible and local resistance <10% 1, 2
• Trimethoprim-sulfamethoxazole 160/800 mg PO twice daily for 14 days if susceptible but fluoroquinolone-resistant 1, 2
• Cefpodoxime 200 mg PO twice daily for 10 days if susceptible and cross-reactivity risk is acceptable 1, 2

Monitoring and Reassessment

• Reassess at 72 hours if there is no clinical improvement with defervescence 2
• Replace indwelling catheters that have been in place for ≥2 weeks at treatment initiation, as this hastens symptom resolution and reduces recurrence risk 2
• Obtain repeat imaging (ultrasound or CT) if patient remains febrile after 72 hours to rule out obstruction, abscess, or other complications 1
• Adjust therapy based on culture and susceptibility results to ensure effective treatment and practice antibiotic stewardship 1, 2