Antibiotic Combo Raises Kidney Injury Risk in the ICU

A commonly used antibiotic combination was significantly associated with increased risk of acute kidney injury among ICU patients, based on data from more than 35,000 individuals.

Concomitant vancomycin and piperacillin/tazobactam (VPT) remain widely used for the initial management of ICU patients with suspected infections, but it has been linked to acute kidney injury in general medical studies, wrote Alyssa Y. Chen, an MD/MPH candidate at the University of Texas Southwestern Medical Center, Dallas, and colleagues.

However, previous studies of ICU patients in particular have been inconclusive and lacking in comparison with other treatments, they said.

In a study published in the journal Chest, the researchers reviewed data from 35,654 adults admitted to ICUs at 335 hospitals between 2010 and 2015. Of these, 27,459 received VPT; 6371 received vancomycin and cefepime (VC); and 1824 received vancomycin and meropenem (VM). Acute kidney injury (AKI) was defined as stages 2 or 3 on the Kidney Disease: Improving Global Outcomes (KDIGO) scale. The primary outcome was AKI; secondary outcomes included initiation of dialysis, dialysis-free survival, and in-hospital mortality.

In a propensity scoring matched analysis, patients treated with VPT had a significantly higher risk of AKI compared with both VC and VM, with odds ratios (OR) of 1.37 and 1.27, respectively. VPT also was associated with increased risk for dialysis compared with both VC and VM, (OR, 1.28 and 1.56, respectively). However, VPT also was associated with increased odds of dialysis-free survival compared with both VC and VM (OR, 1.14 and 1.28, respectively). Mortality rates were similar among the three groups.

In a subgroup analysis of treatment duration and baseline renal function, patients without renal insufficiency at baseline and those who underwent longer treatments (48 hours or longer) with VPT had the highest risk of AKI.

The findings were limited by several factors including the retrospective design and the inability to analyze urine output, and randomized trials that include urine output are needed to support the results, the researchers noted.

In addition, "multi-center, large-scale studies with kidney functional and stress biomarkers in addition to kidney biopsy results are needed to better distinguish the nephrotoxic potential of VPT compared to VC and VM," they wrote in their discussion.

However, the results were strengthened by the large sample size, diverse study population, and use of propensity score matching, the researchers said. Antibiotic decisions should involve consideration of patient-specific factors including history and clinical condition, local antibiotic resistance patterns, risk of neurotoxicity and Clostridium difficile infection, allergy profiles, and colonization with multidrug-resistant organisms, but the current study supports consideration of VM or VC over VPT to reduce nephrotoxicity risk and the risk for adverse clinical outcomes, they concluded.

The study received no outside funding. The researchers report no relevant financial relationships.  

CHEST. Published April 9, 2023. Abstract.

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Cite this: Antibiotic Combo Raises Kidney Injury Risk in the ICU - Medscape - Apr 26, 2023.