Is Meropenem (Merrem)-Vaborbactam approved in India for the treatment of complicated urinary tract infections?

Meropenem-Vaborbactam Approval Status in India for Complicated UTIs

Meropenem-vaborbactam is not currently approved in India for the treatment of complicated urinary tract infections. While this combination antibiotic has received approval from the U.S. FDA in August 2017 for complicated UTIs, there is no evidence in the provided literature indicating its approval or availability in India 1.

Background on Meropenem-Vaborbactam

Meropenem-vaborbactam is a combination of:

• A carbapenem antibiotic (meropenem)
• A novel β-lactamase inhibitor (vaborbactam) with activity against class A carbapenemases, particularly KPC 2, 3

Global Approval Status and Indications

• Approved by the U.S. FDA in August 2017 specifically for complicated UTIs including pyelonephritis 1, 2
• Demonstrated efficacy in the TANGO-I and TANGO-II clinical trials 1, 4
• Recommended dosage is 4g (2g meropenem-2g vaborbactam) IV every 8 hours 1

Clinical Evidence Supporting Its Use

• In the TANGO-I trial, meropenem-vaborbactam showed:

  • Non-inferiority and statistical superiority compared to piperacillin-tazobactam for complicated UTIs 4
  • Overall success rate of 98.4% versus 94.0% with piperacillin-tazobactam 4

• In the TANGO-II trial, it demonstrated:

  • Efficacy against carbapenem-resistant Enterobacteriaceae (CRE) infections 2
  • Decreased 28-day mortality compared to best available therapy 2

Recommendations for CRE-UTIs in Guidelines

Current guidelines for treating CRE-UTIs recommend:

• Meropenem-vaborbactam 4g IV q8h for complicated UTIs caused by CRE (Weak recommendation, low quality of evidence) 1
• Alternative options include:
  • Ceftazidime-avibactam 2.5g IV q8h (Weak recommendation, very low quality of evidence) 1
  • Imipenem-cilastatin-relebactam 1.25g IV q6h (Weak recommendation, low quality of evidence) 1
  • Plazomicin 15 mg/kg IV q12h (Weak recommendation, very low quality of evidence) 1

Safety Profile

• Generally well-tolerated with adverse events reported in 39.0% of patients (compared to 35.5% with piperacillin-tazobactam) 4
• Common side effects include:
  • Elevated liver enzymes (ALT, AST) 5
  • Infusion site phlebitis 5
• Important drug interactions:
  • Competes with probenecid in renal tubular secretion 5
  • Reduces valproic acid blood levels, potentially increasing seizure risk 5

Clinical Implications for Practice in India

• For treating complicated UTIs caused by CRE in India, clinicians must rely on other approved alternatives 1
• The European Association of Urology guidelines (2024) list meropenem-vaborbactam as an option only for patients with multidrug-resistant organisms, not for routine use 1
• For patients in India requiring treatment for CRE infections, consultation with infectious disease specialists is warranted to determine the most appropriate available alternatives 1

Conclusion

While meropenem-vaborbactam represents an important addition to the antimicrobial arsenal against CRE infections, particularly for complicated UTIs, it is not currently approved for use in India. Clinicians in India must rely on other available treatment options for managing complicated UTIs, including those caused by resistant pathogens 1.