A new clinical guideline recommends a tiered treatment strategy for managing complicated urinary tract infections (cUTIs), emphasizing illness severity, risk of resistance, shorter antibiotic courses, and timely oral transitions.

Initial empiric antibiotic selection should be guided by whether the patient presents with sepsis. For patients with cUTI and sepsis, preferred initial agents include third- or fourth-generation cephalosporins, carbapenems, piperacillin–tazobactam, or fluoroquinolones. For patients without sepsis, initial therapy should favor third- or fourth-generation cephalosporins, piperacillin–tazobactam, or fluoroquinolones over carbapenems, novel beta-lactam–beta-lactamase inhibitors, cefiderocol, plazomicin, or older aminoglycosides.

The guidance outlines a four-step framework for empiric therapy: assess illness severity, identify resistance risk factors, evaluate drug safety, and consult local antibiogram data in cases of sepsis. Sepsis is defined as a ≥2-point increase in Sequential Organ Failure Assessment (SOFA) score. For septic shock—requiring vasopressors and lactate concentration >2 mmol/L—antibiotics should cover ≥90% of likely pathogens based on the antibiogram.

Patients with a history of urinary isolates resistant to a particular antibiotic should not receive that agent empirically. Fluoroquinolones should be avoided if used within the previous 12 months.

For clinically improving patients receiving intravenous (IV) antibiotics who can tolerate oral medications, the guideline suggests early transition to oral therapy when effective oral options are available. Recommended agents include ciprofloxacin (70% absorption, 40% to 50% urinary excretion), levofloxacin (99% absorption, 64% to 100% urinary excretion), and trimethoprim–sulfamethoxazole (70% to 90% absorption; 84% and 66% urinary excretion, respectively).

The recommended duration of treatment is 5 to 7 days for fluoroquinolones and 7 days for non-fluoroquinolone agents in clinically improving patients. For patients with Gram-negative bacteremia, the guideline recommends 7 days of therapy. Duration is calculated from the first day of effective treatment, regardless of route.

Once culture data are available, the guideline emphasizes de-escalating from broad-spectrum empiric therapy to narrow-spectrum targeted agents, guided by susceptibility results.

“This recommendation places a high value on de-escalating antibiotic therapy based on culture results while optimizing effectiveness and minimizing recurrence,” said Barbara W. Trautner, MD, of the Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, and a guideline author.

Nitrofurantoin and oral fosfomycin are not recommended for cUTIs due to poor renal and systemic penetration. The recommendations do not apply to bacterial prostatitis, epididymitis, or orchitis.

Patients with indwelling catheters, structural abnormalities, immunocompromise, or urinary obstruction may require individualized approaches. Male patients with suspected acute bacterial prostatitis may need longer treatment, although supporting evidence is limited.

All recommendations are conditional and based on very low to moderate certainty evidence. The guideline prioritizes early effective therapy, safety, and antimicrobial stewardship to improve outcomes and reduce resistance in both inpatient and outpatient settings.

Source: IDSA