New evidence-based recommendations prioritize timely, targeted therapy and a symptom-focused classification to optimize treatment outcomes and antimicrobial stewardship.
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Image credits: IDSA
The Infectious Diseases Society of America (IDSA) has released its first-ever clinical guidelines for the treatment and management of complicated urinary tract infections (cUTIs). These guidelines provide evidence-based recommendations for clinicians managing patients with cUTIs in both inpatient and outpatient settings.1
The new guidelines introduce a stepwise framework for empiric antibiotic selection, emphasize timely de-escalation to targeted therapy based on urine culture results, and update the clinical classification of uncomplicated vs complicated UTIs. Unlike previous frameworks, the updated classification focuses on observable symptoms, such as fever or catheter use, rather than underlying anatomical issues, with the aim of enhancing decision-making at the point of care.1
Key recommendations include prioritizing third- or fourth-generation cephalosporins, carbapenems, piperacillin-tazobactam, or fluoroquinolones for patients with sepsis. In patients without sepsis, narrower-spectrum options are preferred to preserve antimicrobial stewardship. A four-step approach is proposed to guide empiric therapy:1
The guidelines emphasize transitioning to a narrower, definitive antibiotic regimen once urine culture and susceptibility data become available. This de-escalation is encouraged to reduce the risk of resistance and improve treatment precision.1
These recommendations were developed using the GRADE methodology following a systematic literature review, with endorsement from multiple professional organizations, including SIDP, SHM, ASM, ESCMID, and others. They reflect an urgent need to adapt cUTI management to the growing burden of antimicrobial resistance, particularly among aging patients of all genders.1
The guidelines introduce a four-step framework for empiric antibiotic selection, emphasizing illness severity, resistance risk, patient factors, and local antibiograms.
Early de-escalation to narrower-spectrum antibiotics based on urine culture results is strongly encouraged to combat antimicrobial resistance.
The updated clinical classification shifts focus to observable symptoms like fever and catheter use, improving practical decision-making at the point of care.
Previous reports support and help contextualize the newly released IDSA guidelines for the treatment and management of cUTIs. Examples include recent findings from both the PIVOT-PO trial2 of tebipenem HBr and the PROVE study3 of cefiderocol, each reinforcing key elements of the IDSA’s structured, evidence-based approach.
For example, as we previously reported, the PIVOT-PO phase 3 trial evaluating oral tebipenem HBr demonstrated noninferiority to IV imipenem-cilastatin in treating hospitalized adults with cUTIs, including pyelonephritis. These data align with the guideline’s focus on appropriate empiric therapy and the timely IV-to-oral switch. The potential FDA approval of tebipenem HBr would offer a much-needed oral carbapenem option, supporting outpatient management and reducing hospital burden, both of which are highlighted in the guidelines as important considerations for therapy duration and route of administration.2
Similarly, findings from the PROVE study on cefiderocol reinforce the guideline’s emphasis on early, targeted therapy based on illness severity and resistance risk. In the European cohort, higher clinical cure rates were observed when cefiderocol was used as empiric or documented therapy, compared with salvage use. This supports the IDSA’s four-step framework for antibiotic selection in cUTI, which urges clinicians to weigh factors like prior culture data and the likelihood of encountering resistant pathogens when selecting empiric treatment, especially in severely ill or septic patients.3
Together, these studies illustrate the real-world relevance of the new IDSA recommendations, particularly the need for flexible, individualized treatment strategies based on infection severity, resistance risk, and patient-specific factors.
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