Is meropenem (carbapenem antibiotic) nephrotoxic?

Meropenem and Nephrotoxicity

Meropenem is not considered nephrotoxic and has an excellent renal safety profile compared to many other antibiotics. 1, 2

Safety Profile of Meropenem

• Meropenem demonstrates minimal nephrotoxicity, making it suitable for use in patients with renal impairment when dosage is appropriately adjusted 2
• Unlike imipenem, meropenem is relatively stable to hydrolysis by dehydropeptidase I (DHP-I), eliminating the need for co-administration with cilastatin (a renal enzyme inhibitor), which contributes to its favorable renal safety profile 1, 2
• When meropenem was used in cystic fibrosis patients, only transient elevations of serum transaminases were reported, with no significant renal adverse effects 3
• Studies specifically examining meropenem in elderly and renally impaired patients showed no clinically significant mean change in indicators of renal function between baseline and end of treatment 4

Comparison with Other Antimicrobials

• Aminoglycosides and polymyxins (colistin) are known to be significantly more nephrotoxic than carbapenems like meropenem 3
• In a before-after retrospective study comparing colistin and polymyxin B among critically ill patients, colistin showed higher RIFLE-defined nephrotoxicity (adjusted HR 2.27,95% CI 1.35-3.82) compared to polymyxin B, while carbapenems like meropenem were not associated with such nephrotoxicity 3
• In a retrospective cohort study comparing ceftolozane-tazobactam with polymyxins or aminoglycosides for MDR/XDR Pseudomonas aeruginosa infections, nephrotoxicity was significantly lower with ceftolozane-tazobactam (adjusted OR 0.08,95% CI 0.03-0.22) 3

Renal Considerations and Dosing

• Approximately 70% of meropenem is excreted via the kidneys, necessitating dosage adjustments in patients with renal impairment 1, 5
• The half-life of meropenem (approximately 1 hour in healthy volunteers) is prolonged up to 13.7 hours in anuric patients with end-stage renal disease, requiring appropriate dosage modification 5
• Both standard dosages of meropenem (0.5 and 1.0 g, IV every 8 h) are generally well tolerated even in elderly and/or renally impaired patients 4

Clinical Implications

• Meropenem is often recommended in guidelines for serious infections, including nosocomial pneumonia and complicated urinary tract infections, partly due to its favorable safety profile 3
• When treating severe infections caused by carbapenem-resistant organisms, meropenem-vaborbactam is suggested as a preferred option, with nephrotoxicity not being a significant concern 3
• European guidelines for treatment of multidrug-resistant gram-negative bacilli infections recommend meropenem-containing regimens without specific nephrotoxicity warnings, unlike recommendations for aminoglycosides or polymyxins 3

Monitoring Considerations

• While meropenem itself is not nephrotoxic, standard monitoring of renal function is still recommended during therapy, especially in critically ill patients or those receiving other potentially nephrotoxic medications 5
• Unlike aminoglycosides or vancomycin, therapeutic drug monitoring is not routinely required for meropenem solely for nephrotoxicity concerns 3

In conclusion, meropenem has a favorable renal safety profile compared to many other antibiotics used for serious infections, particularly aminoglycosides and polymyxins, making it a suitable option for patients with or at risk for renal impairment when dosed appropriately.