Is it okay to continue Empagliflozin (Empagliflozin) in a patient with urosepsis?

Empagliflozin Should Be Discontinued in Urosepsis from CAUTI

Empagliflozin must be stopped immediately in a patient with urosepsis from catheter-associated urinary tract infection (CAUTI). The FDA label explicitly warns about urosepsis and pyelonephritis as serious complications requiring prompt evaluation and treatment, and the drug's mechanism of increasing urinary glucose creates an optimal environment for bacterial proliferation during an active severe infection 1.

Primary Rationale for Discontinuation

FDA-Mandated Warning on Urosepsis

• The FDA prescribing information for empagliflozin specifically lists "Urosepsis and Pyelonephritis" as a boxed warning, stating clinicians must "evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated" 1.
• Postmarketing surveillance identified urosepsis and pyelonephritis as serious adverse reactions requiring drug discontinuation 1.
• At least one documented case of septic shock from pyelonephritis and bacteremia occurred in a patient taking empagliflozin, requiring ICU admission and drug discontinuation 2.

Mechanism-Based Concerns in Active Infection

• SGLT2 inhibitors like empagliflozin increase urinary glucose excretion by design, creating a glucose-rich urinary environment that promotes bacterial growth during active UTI 1.
• In urosepsis, achieving "optimal pharmacodynamic exposure to antimicrobials both in blood and in the urinary tract" is critical for survival 3, 4.
• Continuing empagliflozin during active urosepsis directly contradicts the goal of eliminating the nutrient-rich environment bacteria require 5.

Acute Kidney Injury Risk in Sepsis

Volume Depletion and Hemodynamic Instability

• The FDA label warns that empagliflozin causes volume depletion through osmotic diuresis, requiring assessment and correction of volume status before initiation, particularly in patients with renal impairment or those on diuretics 1.
• Urosepsis presents with hemodynamic instability (systolic BP ≤100 mmHg per qSOFA criteria), making the volume-depleting effects of empagliflozin particularly dangerous 6.
• The FDA specifically recommends "temporarily discontinuing in settings of reduced oral intake or fluid losses" and states "if acute kidney injury occurs, discontinue and promptly treat" 1.

Renal Function Monitoring Requirements

• The FDA mandates discontinuation if eGFR falls persistently below 45 mL/min/1.73 m² 1.
• Sepsis-associated acute kidney injury is common in urosepsis, with mortality rates of approximately 10% for catheter-associated bacteremia 6.
• Diabetes is identified as a high-risk factor for CAUTI development, and these patients are already at baseline higher risk for renal complications 6.

Management of CAUTI-Associated Urosepsis

Immediate Treatment Priorities

• Catheter management: Replace or remove the indwelling catheter before starting antimicrobial therapy per strong EAU recommendations 6.
• Empirical antibiotics: Initiate IV third-generation cephalosporin plus aminoglycoside, or amoxicillin plus aminoglycoside within the first hour 6.
• Source control: Early identification and control of urinary tract obstruction is critical, as catheterization duration is the most important risk factor for CAUTI development 6.

Antibiotic Considerations

• Treat symptomatic CAUTI according to complicated UTI recommendations with 7-14 days of therapy (14 days for men when prostatitis cannot be excluded) 6.
• Urine and blood cultures must be obtained before antibiotic initiation 6.
• Avoid fluoroquinolones for empirical treatment in urology patients or those who used fluoroquinolones in the last 6 months 6.

When to Consider Restarting Empagliflozin

Post-Resolution Criteria

• Only consider restarting after complete resolution of infection, documented by clinical improvement (afebrile >48 hours, hemodynamic stability) and negative cultures 6.
• Ensure eGFR has recovered to >45 mL/min/1.73 m² and volume status is optimized 1.
• Reassess the risk-benefit ratio given the patient's documented susceptibility to serious UTI on this medication 2.

Alternative Diabetes Management During Acute Illness

• Transition to insulin-based regimens during acute sepsis, as glycemic control remains essential but empagliflozin's risks outweigh benefits in this setting 6.
• Monitor for hypoglycemia if continuing other diabetes medications, as sepsis alters glucose metabolism 1.

Critical Pitfalls to Avoid

• Do not continue empagliflozin based solely on good prior glycemic control—the mortality risk from untreated or inadequately treated urosepsis (30-40% in severe sepsis/septic shock) far exceeds any glycemic benefit 4.
• Do not delay discontinuation pending culture results—the FDA warning is based on mechanism of action and postmarketing cases, not culture-dependent 1.
• Do not restart prematurely before confirming infection resolution and renal function recovery, as recurrent serious UTI has been documented after empagliflozin continuation 2.