What is the risk of additive nephrotoxicity when vancomycin and meropenem (Merrem) are coadministered, potentially leading to Impaired renal function?

From the Guidelines

Coadministration of vancomycin and meropenem does not typically cause additive nephrotoxicity requiring dose adjustments in patients with normal renal function. While vancomycin alone carries a risk of nephrotoxicity (approximately 5-25% depending on dosing and patient factors) [ 1 ], meropenem has minimal nephrotoxic potential. When using these antibiotics together, standard monitoring of renal function is sufficient rather than special precautions. For vancomycin, target trough levels of 10-15 mg/L for most infections or 15-20 mg/L for severe infections like endocarditis or osteomyelitis are recommended, with dose adjustments based on these levels and renal function [ 1 ]. Meropenem is typically dosed at 1g IV every 8 hours for most severe infections, with adjustments for renal impairment. The combination is commonly used for empiric coverage of severe infections where both gram-positive (including MRSA) and gram-negative pathogens are suspected. While not synergistically nephrotoxic, patients with risk factors such as pre-existing renal disease, advanced age, or concomitant use of other nephrotoxic agents should be monitored more closely with regular assessment of renal function (BUN, creatinine) every 2-3 days during therapy. It's also worth noting that the use of vancomycin with other nephrotoxic agents, such as gentamicin, can increase the risk of nephrotoxicity [ 1 ]. However, the combination of vancomycin and meropenem is not specifically mentioned as having increased nephrotoxicity risk in the provided evidence. Therefore, the focus should be on standard monitoring and dose adjustments based on renal function and vancomycin trough levels.

From the FDA Drug Label

Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Additional risk factors for AKI in patients receiving vancomycin include receipt of concomitant drugs known to be nephrotoxic, in patients with pre-existing renal impairment, or with co-morbidities that predispose to renal impairment

The coadministration of vancomycin and meropenem may increase the risk of additive nephrotoxicity, potentially leading to impaired renal function, as vancomycin and other nephrotoxic drugs can increase the risk of acute kidney injury (AKI) when used concomitantly 2.

• Key risk factors for AKI in patients receiving vancomycin include:
  • Receipt of concomitant drugs known to be nephrotoxic
  • Pre-existing renal impairment
  • Co-morbidities that predispose to renal impairment It is essential to monitor renal function closely when coadministering vancomycin and meropenem.

From the Research

Risk of Additive Nephrotoxicity

The coadministration of vancomycin and meropenem may increase the risk of additive nephrotoxicity, potentially leading to impaired renal function.

• A case report study 3 found that coadministering vancomycin with high-dose meropenem (6.0 g/day) caused acute kidney injury (AKI), whereas no AKI occurred when vancomycin was administered alone or with a low dose of meropenem (1.5 or 3.0 g/day).
• A comparative study 4 found that vancomycin-associated nephrotoxicity developed less frequently when vancomycin was combined with imipenem-cilastatin than when combined with meropenem.
• A retrospective study 5 found that the incidence of AKI was higher with vancomycin + meropenem (VM) than with vancomycin + cefepime (VC) in trauma patients.
• Another study 6 found that the incidence of AKI was lower in patients receiving vancomycin + meropenem (VM) compared to those receiving vancomycin + piperacillin-tazobactam (VPT).
• A retrospective analysis 7 found that the use of meropenem with vancomycin may be safer than using imipenem-cilastatin sodium with vancomycin, and that careful monitoring of renal function and timely dose adjustment may reduce the occurrence of nephrotoxicity.

Factors Influencing Nephrotoxicity Risk

Several factors may influence the risk of nephrotoxicity when vancomycin and meropenem are coadministered, including:

• Dose of meropenem: High-dose meropenem (6.0 g/day) may increase the risk of AKI 3.
• Combination with other antimicrobials: The use of multiple antimicrobials, including vancomycin and meropenem, may increase the risk of nephrotoxicity 7.
• Patient characteristics: Factors such as diabetes mellitus, obesity, and pre-existing renal disease may increase the risk of nephrotoxicity 5, 7.
• Monitoring and dose adjustment: Regular monitoring of renal function and timely dose adjustment may reduce the risk of nephrotoxicity 7.