PATIENT CONSIDERATIONS

 

Consider patient characteristics and antibiotic resistance when treating uncomplicated urinary tract infections (uUTIs) empirically

 

A retrospective study of US female patients with uUTIs* found that 17% experienced treatment failure† to empirically prescribed oral antibiotics.1

These patient characteristics, identified in a recent study, increased risk for treatment failure1†:

Bacteria icon

History of recurrent uUTIs‡

  • More patients who experienced treatment failure (TF) had recurrent uUTIs than those without TF (22.6% vs 17.0%; standard difference, 14.1%§)1
  • The incidence of TF in patients with recurrent uUTIs was 21.1%, which was higher than the overall TF incidence of 16.7%1
  • Patients with recurrent uUTIs had a 12% higher risk of experiencing TF compared to those without recurrent uUTIs (adjusted risk ratio [aRR] [95% CI]: 1.12 [1.10-1.14])1
See subgroup analysis for patients with a history of recurrent uUTIs
Woman icon

Age 50 years and older

  • Patients aged 50 years and older had a risk of treatment failure ranging from 19% to 35%, with the risk incrementally increasing with age, compared to patients aged 12-17 years1
  • Another retrospective cohort study found that women aged 50 and older were 70% more likely to need a second antibiotic within 28 days compared with the youngest patient group of 12-17 years (26.3% vs 15.0%; odds ratio, 1.7; 95% CI, 1.0-3.1; P<0.0001)2
  • Risk factors for uUTI in older women:
    • Cumulative antibiotic exposure2
    • Reduction in estrogen, causing:
      • Changes in the microbiome that can promote microbial colonization3
      • Bladder/urethral structural changes that lead to reduced urinary flow and increased residual urine volume4
See subgroup analysis for patients >50 years
Antibiotic icon

Previous antibiotic use within the past 12 months

  • Antibiotic use, for any condition(s) within the past year, increased the risk for treatment failure in subsequent uUTIs1‖:
    • 13% with 1 previous antibiotic
    • 26% with 2 previous antibiotics
    • 60% with ≥3 previous antibiotics
  • * 

    Based on data from a retrospective cohort study (N=376,004) that used electronic health records to find information on female patients (aged ≥12 years) who were diagnosed with an uncomplicated UTI and empirically prescribed an antibiotic. Treatment failure was defined as any of the following within 28 days of their initial antibiotic prescription for an uncomplicated UTI: need for 1 or more additional antibiotics, administration of IV antibiotics, or primary diagnosis of a UTI in an acute-care setting (excluding the original UTI diagnosis).1

  • †

    Treatment failure was defined as a uUTI requiring additional clinical intervention within 28 days of initial treatment, which could have included a second antibiotic or an emergency department visit or inpatient stay with a new primary diagnosis of UTI.1 Treatment failure may be defined differently in clinical practice.4

  • ‡

    Defined as a diagnosis of recurrent uUTI, identified in clinician notes, or as 2 UTIs in the past 6 months or 3 UTIs in the past 12 months, including the index uUTI diagnosis.1

  • §

    aRR (95% CI) for treatment failure based on age, compared with the reference group (female patients aged 12-17 years): 50-64 years, 1.19 (1.14-1.24); 65-74 years, 1.27 (1.22-1.33); ≥75 years, 1.35 (1.29-1.41).1

  • Retrospective cohort study of outpatient data from 2366 positive urine cultures collected at 9 facilities across the US from 2087 female outpatients ≥12 years of age who were not hospitalized within 24 hours of culture collection.2

  • ‖

    aRR (95% CI) for previous antibiotic use for any condition within the past 12 months compared with the reference group (female patients with no antibiotic use): 1 antibiotic, 1.13 (1.11-1.16); 2 antibiotics, 1.26 (1.23-1.29); ≥3 antibiotics, 1.60 (1.56-1.64).1

aRR=adjusted risk ratio.

Women at risk of uUTI treatment failure may need more antibiotic options1,2

Paper with checkmark icon

Treatment failure rates are also higher among patients with antibiotic-resistant infections5

Antibiotic resistance is another important consideration when choosing a uUTI treatment. In clinical practice, physicians should consider regional resistance rates when treating uUTIs.6

 

A retrospective cohort study comparing the likelihood of treatment failure** in uUTIs caused by antibiotic-resistant (defined as ESBL+) vs antibiotic-sensitive (defined as ESBL-) uropathogens†† found a 62% higher likelihood of treatment failure in patients with ESBL+ vs those with ESBL- uropathogens.5‡‡

See subgroup analysis for patients with antibiotic-resistant E. coli
  • **

    Assessed in US female outpatients with uUTIs. Treatment failure was defined as the need for a second antibiotic prescription within 28 days of the index uUTI.5

  • ††

    Uropathogens included Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis. ESBL status was determined by commercial test or intermediate/resistant susceptibility test results to ceftriaxone, cefotaxime, ceftazidime, or cefepime. Of 2880 uUTI episodes, 6.6% (n=189) were ESBL+ and 93.4% (n=2691) were ESBL-.5

  • ‡‡

    Re-prescription rate at 28 days with ESBL+ vs ESBL- uropathogens: 38.6% vs 22.3%. Likelihood of 28-day re-prescription with ESBL+: adjusted OR 1.62 (95% CI: 1.16-2.25), P=0.0045.5

Indication & Important Safety Info

Indication

Important Safety Information

Indication

BLUJEPA is indicated for the treatment of female adult and pediatric patients 12 years of age and older weighing at least 40 kilograms (kg) with uncomplicated urinary tract infections (uUTI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis.

Usage to Reduce Development of Drug-Resistant Bacteria

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

Important Safety Information

CONTRAINDICATIONS

BLUJEPA is contraindicated in patients with a history of severe hypersensitivity to BLUJEPA.

WARNINGS AND PRECAUTIONS

QTc Prolongation

  • A dose and concentration-dependent prolongation of the QTc interval has been observed with BLUJEPA. Avoid use of BLUJEPA in patients with a history of QTc prolongation or with relevant pre-existing cardiac disease, patients taking antiarrhythmic agents, and in patients receiving drugs that prolong the QT interval. Due to an increase in BLUJEPA exposure, avoid concomitant administration of BLUJEPA with strong CYP3A4 inhibitors, in patients with severe hepatic impairment (Child-Pugh Class C), and in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min).

Acetylcholinesterase Inhibition

  • Dysarthria and other adverse reactions potentially attributed to acetylcholinesterase inhibition have been reported with BLUJEPA, an acetylcholinesterase inhibitor. Increased cholinergic effects can be associated with severe adverse effects, including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope. Monitor patients with underlying medical conditions that may be exacerbated by acetylcholinesterase inhibition and patients receiving succinylcholine-type neuromuscular blocking agents, systemic anticholinergic medications, or non-depolarizing neuromuscular blocking agents.

Hypersensitivity Reactions

  • Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving BLUJEPA. If an allergic reaction to BLUJEPA occurs, discontinue the drug and institute appropriate supportive measures.

Clostridioides difficile-Associated Diarrhea

  • Clostridioides difficile infection (CDI) has been reported with nearly all systemic antibacterial agents, including BLUJEPA. Evaluate patients who develop diarrhea.
ADVERSE REACTIONS
  • The most common adverse reactions occurring in ≥1% of patients are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis.
DRUG INTERACTIONS
  • CYP3A4 Inhibitors: Avoid coadministration of BLUJEPA with strong CYP3A4 inhibitors due to increased gepotidacin exposure.
  • CYP3A4 Inducers: Avoid coadministration of BLUJEPA with strong CYP3A4 inducers due to decreased gepotidacin exposure.
  • CYP3A4 Substrates: Avoid coadministration of BLUJEPA with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic window.
  • Digoxin: Due to an increase in digoxin exposures, consider monitoring digoxin serum concentration, as appropriate, with concomitant administration of BLUJEPA.
USE IN SPECIFIC POPULATIONS
  • Renal Impairment: Avoid use of BLUJEPA in patients with severe renal impairment with eGFR <30 mL/min, including those receiving dialysis.
  • Hepatic Impairment: Avoid use of BLUJEPA in patients with severe hepatic impairment (Child-Pugh Class C).

Please see accompanying Prescribing Information, including Medication Guide, for BLUJEPA. 

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. Fromer DL, Luck ME, Cheng WY, et al. Risk factors for treatment failure in US female outpatients with uncomplicated urinary tract infection: an observational study. J Gen Intern Med. 2024. doi:10.1007/s11606-024-09029-6

  2. Trautner BW, Kaye KS, Gupta V, et al. Risk factors associated with antimicrobial resistance and adverse short-term health outcomes among adult and adolescent female outpatients with uncomplicated urinary tract infection. Open Forum Infect Dis. 2022;9(12):ofac623. doi:10.1093/ofid/ofac623

  3. Aydin A, Ahmed K, Zaman I, Khan MS, Dasgupta P. Recurrent urinary tract infections in women. Int Urogynecol J. 2015;26(6):795-804. doi:10.1007/s00192-014-2569-5

  4. Sihra N, Goodman A, Zakri R, Sahai A, Malde S. Nonantibiotic prevention and management of recurrent urinary tract infection. Nat Rev Urol. 2018;15(12):750-776. doi:10.1038/s41585-018-0106-x

  5. Patel R, Gupta V, Preib MT, et al. Impact of extended-spectrum β-lactamase-positivity in urine isolates on outcomes in female patients with uncomplicated urinary tract infection. Poster presented at: 33rd European Congress of Clinical Microbiology & Infectious Diseases 2023; April 15-18, 2023; Copenhagen, Denmark.

  6. Kaye KS, Gupta V, Mulgirigama A, et al. Antimicrobial resistance trends in urine Escherichia coli isolates from adult and adolescent females in the United States from 2011 to 2019: rising ESBL strains and impact on patient management. Clin Infect Dis. 2021;73(11):1992-1999. doi:10.1093/cid/ciab560