cUTI CONSIDERATIONS

 

Challenges in the management of cUTI

Important treatment considerations for cUTI include1-3:

  • Hospitalization for IV antibiotics3

  • Rising antibiotic resistance1,2

cUTIs can contribute to clinical and economic burden across care settings3-5

~3 million cases of cUTI occur in the US each year.3*

>600,000 cUTI-related hospital admissions were seen in a 2018 US database study, accounting for 1 in every 500 total hospitalizations.5†

Median hospital length of stay for non-catheter-associated cUTI was 5 days (interquartile range: 3 to 8 days).5†

In a separate retrospective review of adult patients receiving IV carbapenem for cUTI‡ using stringent discharge criteria§:
35% were clinically ready for discharge before actual discharge (average 2.9 additional days‖).4

  • *

    Retrospective study of a PharmMetrics Plus database (2011-2017) (N=688,820). Patients were ≥18 years old with a cUTI diagnosis, with continuous enrollment for ≥6 months pre- and ≥30 days post-index dates. Two cohorts were identified based on the setting of the first cUTI diagnosis: inpatient or outpatient.3

  • †

    Cross-sectional multicenter study of 20%-stratified sample of discharges from US community hospitals from the National Inpatient Sample database (2018), with a total of 2,837,385 discharges with a UTI code. Of all UTI admissions, 626,520 were considered cUTI, of which 79.9% were considered non-catheter-associated cUTIs, and the remainder were considered catheter associated UTIs.5

  • ‡

    Retrospective review of EHRs and unstructured clinical notes from Mass General Brigham Research Patient Data Registry of adult patients (N=333) receiving IV carbapenem for cUTI with a positive urine culture between January 2019 and June 2024. This is a GSK-sponsored study. This study does not exclude patients requiring co-administration of other IV therapies.4

  • §

    Based on a stringent rule-based definition for clinically ready for discharge, in which missing data were imputed based on the last observation of clinically ready for discharge criterion carried forward. Additionally, the definition of “clinically ready for discharge” is not standardized and may vary by institution.4

  • ‖

    Mean difference; range of 1.0 to 8.0 days.4

  • cUTI=complicated urinary tract infection; EHR=electronic health record; IV=intravenous; UTI=urinary tract infection.

Rising antimicrobial resistance can limit oral treatment options for patients with cUTI

Over the last 20 years, rates of ESBL+ Enterobacterales in the US have increased 16.1% in community-acquired UTIs and 21% in healthcare-associated UTIs.1¶

In UTI caused by ESBL+ Enterobacterales in hospitalized patients in the US, 36.1% were resistant to FQs, 33.6% were resistant to TMP-SMX, and 2.4% were resistant to carbapenems.2#

In patients hospitalized for non-carbapenem-resistant cUTI,**
13.0% had a triple-resistant pathogen.††
Of these, 43.3% received an empiric carbapenem.6

  • For community-acquired: up from 0.2% to 16.3%; for healthcare-associated: up from 4.0% to 25.0%. Data from a 2022 literature review including studies from France, Italy, Germany, Spain, the UK, and the US. Studies of community-acquired UTIs included outpatients and emergency department patients; studies of healthcare-associated UTIs included inpatients and those in long-term facilities.1

  • #

    Prospective observational study of adults hospitalized for UTI in 11 US hospital emergency departments (2018-2019) that included 527 patients and 473 Enterobacteriaceae urine and blood isolates. FQs included ciprofloxacin and levofloxacin; carbapanems included doripenem, ertrapenem, imipenem, and meropenem.2

  • **

    Multicenter, retrospective cohort study of hospitalized patients with culture-positive non-carbapenem-resistant cUTI using data from the Premier Research database for years 2013 through 2018 (N=23,331).6

  • ††

    Defined as resistance to ≥3 of the following: 3rd-generation cephalosporin, fluoroquinolones, TMP-SMX, fosfomycin, and nitrofurantoin.6

  • cUTI=complicated urinary tract infection; E. coli=Escherichia coli; ESBL+=extended-spectrum beta-lactamase positive; FQ=fluoroquinolone; TMP-SMX=trimethoprim/sulfamethoxazole; UTI=urinary tract infection.

2025 IDSA guidelines for cUTI provide recommendations on timing of transition from IV to oral antibiotics7

The 2025 IDSA cUTI guidelines state7:

In patients with cUTI (including acute pyelonephritis) treated initially with parenteral therapy who are clinically improving, able to take oral medication, and for whom an effective oral option‡‡ is available, the IDSA suggests transitioning to oral antibiotics rather than continuing parenteral therapy for the remaining treatment duration (conditional recommendation, low certainty of the evidence§§)‖‖

Context and limitations of the 2025 IDSA cUTI guidelines

 

This recommendation places a high value on reducing avoidable intravenous catheter-related adverse events, costs, and resources, as well as taking into account practical aspects of antibiotic administration.7 This does not suggest that oral antibiotics will reduce avoidable intravenous catheter-related adverse events, costs, and resources.

 

The trials supporting this recommendation mostly excluded patients with indwelling urinary catheters, sepsis or septic shock, immunocompromised states, severe renal insufficiency, and functional or structural abnormalities of the urinary tract. Some patients in these subpopulations may need an individualized plan of therapy.7

  • ‡‡

    An effective antimicrobial agent means that the antibiotic achieves therapeutic levels in the urine and relevant tissue and is active against the causative pathogen.7

  • §§

    The trials supporting this recommendation mostly excluded patients with indwelling urinary catheters, sepsis or septic shock, immunocompromised states, severe renal insufficiency, and functional or structural abnormalities of the urinary tract. Some patients in these subpopulations may need an individualized plan of therapy.7

  • ‖‖

    The 2025 IDSA cUTI guidelines were published prior to the approval of an oral carbapenem.

cUTI=complicated urinary tract infection; IDSA=Infectious Diseases Society of America; IV=intravenous.

Review 2 profiles of patients with cUTI

MEET BLAIR & ANTHONY

Indication & Important Safety Info

Indication

Important Safety Information

Indication

UTEBZI is indicated for the treatment of adults with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis, who have limited or no alternative oral treatment options.

Usage to Reduce Development of Drug-Resistant Bacteria

To reduce the development of drug-resistant bacteria and maintain effectiveness of UTEBZI and other antibacterial drugs, UTEBZI should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Safety Information

CONTRAINDICATIONS

UTEBZI is contraindicated in patients with hypersensitivity to UTEBZI or other beta-lactam drugs.

UTEBZI is contraindicated in patients with primary or secondary carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam and carbapenem drugs. Before initiating UTEBZI, assess patients for previous hypersensitivity to carbapenems, penicillins, cephalosporins or other beta-lactams. If an allergic reaction to UTEBZI occurs, discontinue, and institute appropriate supportive measures.

Seizures and Other Central Nervous Systems (CNS) Adverse Reactions

  • Seizures and other CNS adverse reactions have been reported in patients receiving therapy with beta-lactam and carbapenem drugs, including UTEBZI. These reactions occurred most commonly in patients with CNS disorders and/or compromised renal function. Monitor patients at risk for convulsive activity. If CNS adverse reactions including seizures occur, evaluate neurologically to determine whether UTEBZI should be discontinued.

Interactions with Valproic Acid

  • Concomitant use of carbapenems, including UTEBZI, with valproic acid or divalproex sodium may reduce the plasma concentration of valproic acid, potentially increasing the risk of breakthrough seizures. Avoid concomitant use of UTEBZI with valproic acid or divalproex sodium.

Carnitine Depletion

  • Clinical manifestations of carnitine deficiency may occur with pivalate-containing compounds, including UTEBZI. UTEBZI is contraindicated in patients with primary and secondary carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency. Do not use UTEBZI beyond the recommended treatment duration. Consider alternative antibacterial therapy in patients at risk for reductions in serum carnitine (eg, patients with significant renal impairment or decreased muscle mass). Concomitant use with valproic acid, valproate, or other pivalate-generating drugs is generally not recommended due to the increased risk of carnitine depletion.

Clostridioides difficile Infection (CDI)

  • Clostridioides difficile infection has been reported with nearly all systemic antibacterial agents, including UTEBZI and may range in severity from mild diarrhea to fatal colitis. CDI is associated with increased morbidity and mortality. Evaluate patients if diarrhea occurs. Careful medical history is necessary since CDI has been reported to occur over 2 months after the administration of antibacterials. Consider discontinuation of ongoing antibacterials if CDI is suspected or confirmed.

Interference with Newborn Screening Test

  • Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in newborn screening. Prompt follow-up of a positive result is recommended.

Development of Drug-Resistant Bacteria

  • Prescribing UTEBZI in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS

  • The most common adverse reactions occurring in ≥1% of patients are diarrhea, headache, nausea, abdominal pain, hepatic enzyme increased, and Clostridioides difficile infection.

DRUG INTERACTIONS

  • Organic anion transporter 1 (OAT1) and OAT3 inhibitors: Concomitant use is generally not recommended due to increased tebipenem plasma concentrations. If concomitant use is necessary, monitor more frequently for adverse reactions associated with UTEBZI.
  • Valproic acid and divalproex sodium: Avoid concomitant use as it may reduce valproic acid plasma concentrations, increasing the risk of breakthrough seizures. If concomitant use is necessary, monitoring of valproic acid serum concentrations is recommended and consider supplemental anticonvulsant therapy.
  • Other pivalate-generating drugs: Concomitant use is generally not recommended due to decreased carnitine plasma concentrations which may increase the risk of carnitine depletion-associated adverse reactions. If concomitant use is necessary, counsel patients to monitor adverse reactions associated with carnitine depletion.
  • Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in the newborn as part of newborn screening. Prompt follow-up of a positive result is recommended.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: There are insufficient data on the use of UTEBZI in pregnant women. There is a pregnancy safety study for UTEBZI. Healthcare providers or patients may report UTEBZI exposure while pregnant by contacting GSK at 1-888-825-5249. Treatment of a pregnant individual with UTEBZI prior to delivery may cause a false positive test for isovaleric acidemia in the newborn as part of newborn screening.
  • Renal Impairment: Tebipenem plasma concentrations increase with decreasing renal function. Dosage adjustments for UTEBZI are recommended for patients with renal impairment (eGFR 15 mL/min to < 60 mL/min). Use in adults with eGFR >150 mL/min is not recommended because it is predicted to decrease tebipenem exposure, which may reduce UTEBZI efficacy. If use is necessary, monitor clinical response closely and counsel patients to promptly report lack of improvement or worsening of their condition.

Please see full Prescribing Information, including Patient Information, for UTEBZI.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. Fernandez M, Gavaghan MB, Al-Taie A, Stone G, El Mahdy Kotb R. Epidemiology of extended spectrum beta-lactamase (ESBL)-producing Enterobacterales and antimicrobial resistance in urinary tract infection (UTI) and acute pyelonephritis (AP). Open Forum Infect Dis. 2013;10(suppl 2):S1249.

  2. Talan DA, Takhar SS, Krishnadasan A, et al. Emergence of extended-spectrum β-lactamase urinary tract infections among hospitalized emergency department patients in the United States. Ann Emerg Med. 2021;77(1):32-43.

  3. Carreno JJ, Tam IM, Meyers JL, Esterberg E, Candrilli SD, Lodise TP Jr. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect Dis. 2019;6(11):ofz446. doi:10.1093/ofid/ofz446

  4. Koenig SP, Ellis JJ, Boettner DR, et al. Difference in clinically ready for discharge status and actual discharge date in hospitalized complicated urinary tract infection patients treated with intravenous carbapenem. Presented at: IDWeek 2025; October 19-22, 2025; Atlanta, GA.

  5. Zilberberg MD, Nathanson BH, Sulham K, Shorff AF. Descriptive epidemiology and outcomes of hospitalizations with complicated urinary tract infections in the United States, 2018. Open Forum Infect Dis. 2022;9(1):ofab591. doi:10.1093/ofid/ofab591

  6. Zilberberg MD, Nathanson BH, Sulham K, Shorr AF. Multiple antimicrobial resistance and outcomes among hospitalized patients with complicated urinary tract infections in the US, 2013-2018: a retrospective cohort study. BMC Infect Dis. 2021;21(1):159. doi:10.1186/s12879-021-05842-0

  7. Trautner BW, Cortés-Penfield NW, Gupta K, et al. IDSA 2025 guideline update on complicated urinary tract infections. https://www.idsociety.org/practice-guideline/complicated-urinary-tract-infections. Accessed May 18, 2026.