Case: An 80-year-old man with Alzheimer’s dementia presents with fever, worsening suprapubic discomfort, and new right flank pain. He began ciprofloxacin the day before for a presumed urinary tract infection (UTI), but his symptoms have progressed. Four months ago, he had a UTI caused by an extended-spectrum β-lactamase-producing (ESBL) Escherichia coli, susceptible to fluoroquinolones and carbapenems. He has a positive urinalysis and meets sepsis criteria. You are asked to assess him for admission. How do the updated 2025 Infectious Diseases Society of America (IDSA) guidelines inform your management?
The 2025 IDSA guidelines are the first major update since 2010.1 The earlier guidance focused exclusively on uncomplicated infections in healthy, premenopausal women, leaving limited direction for men, older adults, and hospitalized patients. Since that time, a growing body of clinical studies on complicated urinary tract infection (cUTI) has expanded the evidence base, prompting a more practical and inclusive approach. The updated guideline refines key definitions, introduces a four-step framework for empiric therapy, and clarifies IV-to-oral transitions and treatment duration. The Society of Hospital Medicine also contributed to these recommendations, ensuring their applicability to current inpatient practice.
Uncomplicated Versus Complicated UTI: New Classification
The updated classification helps hospitalists quickly determine whether a urinary infection is confined to the bladder or has progressed beyond it:
• Uncomplicated UTI: A bladder-limited infection without systemic features, presenting with lower urinary tract symptoms such as dysuria, urgency or frequency, and suprapubic discomfort. Importantly, both men and women can now meet the criteria for uncomplicated infection.
• Complicated UTI (cUTI): Evidence that the infection has extended beyond the bladder— such as fever, systemic signs, bacteremia, flank pain, or the presence of a urinary catheter, stent, intermittent catheterization, or percutaneous nephrostomy tube—classifies the episode as complicated.
Conditions like diabetes, immunocompromise, male gender, or urologic abnormalities no longer automatically make a UTI complicated. These factors may still influence treatment decisions, but they do not define the classification. As a result, both men and women can have uncomplicated UTIs.
These guidelines exclude bacterial prostatitis, epididymitis, and orchitis, which require separate diagnostic and therapeutic approaches.
Four-Step Method for Empiric Antibiotic Selection
The 2025 IDSA guidelines introduce a four-step approach to guide empiric antibiotic selection for suspected cUTI: 1) assess severity of illness (sepsis versus no sepsis), 2) review patient-specific risk factors for resistant uropathogens, 3) consider allergies and meaningful drug interactions, and 4) use a relevant local antibiogram when the patient is septic. Applying these steps together helps clinicians select among the recommended agents (see Table 1), supporting effective early coverage while promoting individualized care and stewardship.
Step 1: Assess Severity—Is the Patient Septic?
When approaching empiric therapy for suspected cUTI, including pyelonephritis, the 2025 IDSA guidelines emphasize beginning with the severity of illness—specifically, whether the patient meets criteria for sepsis.
The guidelines utilize the Sepsis-3 Task Force definition of sepsis as life-threatening organ dysfunction from a dysregulated host response to infection and correspond to a ≥2-point rise in SOFA, or sequential organ failure assessment, score, reflecting an in-hospital mortality greater than 10% (often approximated with qSOFA or Systemic Inflammatory Response Syndrome, or SIRS, in clinical screening).
Suspected cUTI with sepsis
In patients with sepsis attributed to cUTI, initial empiric therapy should prioritize broad-spectrum agents. The guidelines suggest considering a third- or fourth-generation cephalosporin, piperacillin-tazobactam, a carbapenem, or a fluoroquinolone rather than reaching first for the newer β-lactam/β-lactamase-inhibitor combinations, cefiderocol, or aminoglycosides.
Suspected cUTI without sepsis
For clinically stable, non-septic patients, empiric therapy generally mirrors options used in sepsis, including third- or fourth-generation cephalosporins, piperacillin-tazobactam, or fluoroquinolones, while carbapenems and newer agents are reserved for patients with a history of resistant organisms.
Oral empiric options, particularly for outpatient management, include fluoroquinolones and trimethoprim-sulfamethoxazole (TMP-SMX) as preferred agents. Oral β-lactams are listed as alternative options given more limited evidence, with preference for agents that achieve higher oral bioavailability and urinary concentrations, such as third-generation oral cephalosporins (e.g., cefpodoxime) (see IDSA guidelines for recommended antibiotics and dosing). Earlier-generation cephalosporins and other oral β-lactams, such as amoxicillin-clavulanate, have more variable supporting data and should be used empirically only when necessary and with optimized dosing. While some non-septic patients with cUTI may be managed entirely with oral therapy as outpatients, most hospitalists will encounter patients who are ill enough to require admission and parenteral antibiotics.
Step 2: Assess Patient-Specific Risk for Resistant Uropathogens
Incorporate Recent Urine Culture Data (three to six months)
Prior microbiology can meaningfully inform empiric antibiotic selection. The IDSA review found that when empiric antibiotics for a current UTI aligned with a patient’s previous urine culture results, the likelihood of providing active coverage increased by at least sevenfold. More recent cultures, typically within the past three to six months, are most informative. The guidelines recommend avoiding antibiotics to which the patient has previously had a resistant urinary pathogen isolated within this time frame.
Avoid Empiric Fluoroquinolones if Recently Given
Among the various patient-related risk factors evaluated, prior fluoroquinolone exposure within the past 12 months stood out as a strong predictor of resistance to that class. This may reflect both the high background prevalence of fluoroquinolone resistance and the frequency with which fluoroquinolone exposure was assessed across studies. The guideline panel, therefore, advises avoiding empiric fluoroquinolones in patients with recent exposure, with shorter intervals (e.g., less than three months) likely representing an even higher risk for resistance.
Step 3: Evaluate Additional Patient-Specific Considerations
After accounting for severity and resistance risk, therapy should be refined by individual safety considerations—drug allergies, contraindications, renal or hepatic impairment, and clinically meaningful drug-drug interactions. For example, QT-prolonging agents, nephrotoxic combinations, or interactions with anticoagulants should be recognized early to prevent avoidable harm.
Step 4: Use the Local Antibiogram (for Septic Patients)
For patients with sepsis or septic shock from suspected cUTI, the guidelines recommend using a local, recent (up to 12 months) antibiogram that reflects a similar patient population. When applying the antibiogram to refine empiric therapy:
• Septic shock: Choose an antibiotic with at least 90% susceptibility.
• Sepsis without shock: Choose an antibiotic with at least 80% susceptibility.
These thresholds are based on modeling demonstrating increased mortality when initial therapy lacks activity.
For patients without sepsis, the IDSA makes no recommendation on using antibiograms to guide empiric therapy, underscoring a current evidence gap.
Timing of IV-to-Oral Antibiotic Transition for Definitive Therapy
The guidelines note that increasing evidence supports transitioning from intravenous to oral antibiotics earlier in the treatment course for many infections, as effectiveness depends on achieving therapeutic drug levels rather than the route of administration. For cUTI with or without bacteremia, a switch to oral therapy is generally appropriate once three criteria are met:
• Clinical improvement (afebrile, hemodynamically stable, achieved source control)
• Ability to take and absorb oral medication
• Availability of an oral regimen active against the target pathogen and capable of achieving therapeutic levels in the urine, tissue, and bloodstream
Duration of Therapy for cUTI
For patients with complicated UTI who demonstrate clinical improvement on appropriate antibiotics, the updated IDSA guidelines support shorter treatment courses. In most cases, this corresponds to five to seven days of a fluoroquinolone or seven days of a non-fluoroquinolone agent, counted from the first day of active therapy, rather than traditional 10 to 14-day courses. However, treatment duration should be individualized, as some patients may still require 10 to 14 days of therapy, particularly because studies supporting shorter durations excluded individuals with indwelling urinary catheters, severe sepsis, significant immunocompromise, urinary tract abscesses, chronic kidney disease, complete urinary obstruction, or recent urologic procedures.
The guideline’s conditional recommendation for a seven-day non-fluoroquinolone regimen is based on “very low–certainty evidence.” In this context, TMP-SMX is preferred based on available data, whereas oral β-lactams may be considered when fluoroquinolones and TMP-SMX cannot be used.2 Evidence supporting oral β-lactams for cUTI remains limited, with preference for antibiotics that achieve higher oral bioavailability and urinary concentrations, such as third-generation oral cephalosporins (e.g., cefpodoxime). Earlier-generation cephalosporins and other oral β-lactams, including amoxicillin– clavulanate, have more variable supporting data and should be reserved for situations in which other options are less suitable and used with optimized dosing (see IDSA guidelines for recommended antibiotics and dosing). When oral β-lactams are used, treatment duration should be individualized, as most studies evaluating these agents in cUTI have used 10 to 14 days of therapy.3,4
Regardless of regimen, clinicians should reassess patients who fail to improve as expected and evaluate for a persistent nidus of infection or a source-control issue, such as urinary obstruction, infected stone, or catheter-related complications.
Duration of Therapy for cUTI with Gram-Negative Bacteremia
For patients with gram-negative bacteremia from a urinary source who are clinically improving on appropriate therapy, the guidelines similarly support a seven-day treatment course instead of the traditional 14 days. Additional evidence comes from the BALANCE trial, which randomized 3,608 hospitalized patients with bacteremia to seven versus 14 days of antibiotics.5 Most infections were caused by gram-negative organisms, and 42% had a urinary source. The seven-day strategy was non-inferior to 14 days for 90-day mortality, both overall and within the urinary-source subgroup. Importantly, the trial used a pragmatic design, allowing treating clinicians to select antibiotics, dosing, and timing of oral step-down, reflecting real-world practice.
Oral step-down therapy for cUTI with gram-negative bacteremia follows the same duration and antibiotic-selection principles described earlier in the nonbacteremic cUTI section. Fluoroquinolones and TMP-SMX remain the most studied oral step-down options and offer high bioavailability. Evidence supporting oral β-lactams is more limited, but they may be used selectively when fluoroquinolones and TMP-SMX cannot be used, provided the antibiotic is active and achieves adequate serum and urinary concentrations (see IDSA guidelines for recommended antibiotics and dosing). As with non-bacteremic cUTI, treatment duration should be individualized, and some patients may require 10 to 14 days of therapy when stepping down to an oral β-lactam.3,6-9
Back to the Case
Under the updated classification, this patient meets criteria for a cUTI with sepsis but no shock. Using the 4-step framework, his prior urine culture from four months earlier showed ESBL E. coli. The local antibiogram showed acceptable (over 80%) susceptibility to carbapenems for septic patients without shock, supporting IV ertapenem as an appropriate starting agent. By hospital day three, he improved rapidly, and both urine and blood cultures again grew ESBL E. coli, resistant to fluoroquinolones but susceptible to carbapenems and TMP-SMX. With clear clinical response and organism-directed susceptibilities in hand, the guidelines supported an early transition to oral TMP-SMX for a total treatment duration of seven days.
Bottom Line
The 2025 IDSA guidelines simplify UTI classification: bladder-limited infections are uncomplicated, and systemic or upper-tract involvement defines cUTI—in both men and women.
Empiric therapy for cUTI follows a 4-step approach: assess severity, review recent urine cultures (three to six months), account for patient-specific risks, and incorporate the local antibiogram when appropriate.
Patients who are clinically improving on an active regimen can transition early to oral therapy.
For most patients, including those with improving gram-negative bacteremia, a seven-day total course is generally appropriate.
Dr. Farkhondehpo
Dr. Cowell
Dr. Farkhondehpour is an associate clinical professor in the division of hospital medicine and associate program director for the internal medicine residency program in the department of medicine at the University of California, San Diego School of Medicine in San Diego. Dr. Cowell is an associate clinical professor in the division of infectious diseases and global public health and associate program director for the internal medicine residency program in the department of medicine at the University of California, San Diego School of Medicine in San Diego.
Key Takeaways
• Simplified UTI classification: UTIs are now classified as uncomplicated if limited to the bladder without systemic symptoms, and complicated if there is systemic involvement; applicable to men and women.
• Empiric therapy framework: A four-step approach assesses severity, reviews recent urine culture, considers patient-specific risks, and uses local antibiogram data when sepsis is present.
• Severity assessment guides therapy: Patients with sepsis require broad-spectrum IV antibiotics, and stable, non-septic patients who are clinically improving on an active regimen can transition early to oral therapy.
• Importance of recent urine cultures: Prior urine culture results within three to six months significantly improve empiric antibiotic selection.
References
1. Trautner BW, et al. Complicated urinary tract infections (cUTI): clinical guidelines for treatment and management. Infectious Diseases Society of America website. https://www.idsociety.org/practice-guideline/complicated-urinary-tract-infections/. Published July 17, 2025. Accessed March 5, 2026.
2. Fox MT, et al. A seven-day course of TMP-SMX may be as effective as a seven-day course of ciprofloxacin for the treatment of pyelonephritis. Am J Med. 2017;130(7):842-845. doi: 10.1016/j.am-jmed.2017.01.025.
3. Bjork J, et al. Oral ß-lactams compared with fluoroquinolones for Enterobacterales bloodstream infections: a multicenter observational study. Clin Infect Dis. 2023;76(3):e1158–e1166.
4. Hobbs ALV, et al. Rise of the beta-lactams: a retrospective, comparative cohort of oral beta-lactam antibiotics as step-down therapy for hospitalized adults with acute pyelonephritis. Antimicrobial Stewardship & Healthcare Epidemiology. 2024;4(1):e102. doi:10.1017/ash.2024.70.
5. The BALANCE Investigators. Antibiotic treatment for 7 versus 14 days in patients with bloodstream infections. N Engl J Med. 2025;392:1065-1078. DOI: 10.1056/NEJMoa2404991.
6. Saad M, et al. Oral ß-lactam step down in bacteremic E. coli urinary tract infections. BMC Infect Dis. 2020;20(1):785. Doi:10.1186/s12879-020-05498-2.
7. Sutton JD, et al. Oral ß-lactam antibiotics vs fluoroquinolones or trimethoprim-sulfamethoxazole for definitive treatment of enterobacterales bacteremia from a urine source. JAMA Netw Open. 2020;3(10):e2020166. doi: 10.1001/jamanetworkopen.2020.20166.
8. McAlister MJ, et al. Oral ß-lactams vs fluoroquinolones and trimethoprim/ sulfamethoxazole for step-down therapy for Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae bacteremia. Am J Health Syst Pharm. 2023;80(Suppl 1):S33-S41. doi: 10.1093/ajhp/zxac202.
9. Geyer AC, et al. Outcomes of high-dose oral beta-lactam definitive therapy compared to fluoroquinolone or trimethoprim-sulfamethoxazole oral therapy for bacteremia secondary to a urinary tract infection. Antimicrob Steward Healthc Epidemiol. 2023;3(1):e148. doi: 10.1017/ash.2023.435.
