Nephrotoxicity associated with piperacillin-tazobactam (PT) combined with vancomycin (V) has been increasingly reported1,2, with some recommending that an alternative to V be used when PT is also on board 2. However, there are several reasons why the nephrotoxic potential of PT either alone or with antibiotics other than V also deserves further study before such recommendations can be widely embraced3.
First, most studies of VPT combination do not include comparative V or PT alone arms making it difficult to assess the relative contribution of these 2 antibiotics to kidney injury when used in combination. A small study that did include a PT-only arm reported a similar rate of acute kidney injury (AKI) in PT and VPT arms ( 15.4% and 18.8% , respectively), both significantly higher that than of V-only group (4%).4
Other reasons not to readily dismiss PT as a cause of nephrotoxicity include the lack of association between higher V trough levels and AKI in patients receiving VPT2, the association of PT with lower rates of renal function recovery in critically ill patients when compared to other selected β-lactams5, and higher magnesium and potassium renal tubular loss with the use of PT compared to selected cephalosporins and ciprofloxacin6. As with other penicillins, PT-associated acute interstitial nephritis may also occur7-8.
In short, even in the absence of V, nephrotoxic potential of PT should not be automatically dismissed.
Update: Since the original posting of this pearl, an in-depth article on the subject was published in 2021 (https://www.karger.com/Article/Pdf/513742)
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- Hammond DA, Smith MN, Chenghui Li, et al. Systematic review and meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam. Clin Infect Dis 2017;64:666-74.
- Navalkele B, Pogue JM, Karino S, et al. Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime. Clin Infect Dis 2017;64:116-123.
- Manian FA. Should we revisit the nephrotoxic potential of piperacillin-tazobactam as well? Clin Infect Dis 2017; https://doi.org/10.1093/cid/cix321
- Kim T, Kandiah S, Patel M, et al. Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. BMC Res Notes 2015;8:579.
- Jensen J-U S, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomized trial. BMJ Open 2012;2:e000635. http://bmjopen.bmj.com/content/2/2/e000635
- Polderman KH, Girbes ARJ. Piperacillin-induced magnesium and potassium loss in intensive care unit patients. Intensive Care Med 2002;28:530-522.
- Muriithi AK, Leung N, Valeri AM, et al. Clinical characteristics, causes and outcomes of acute interstitial nephritis in the elderly. Kidney International 2015;87:458-464.
- Soto J, Bosch JM, Alsar Ortiz MJ, et al. Piperacillin-induced acute interstitial nephritis. Nephron 1993;65:154-155.
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