Association of vancomycin plus piperacillin–tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study

Miano, Todd A.; Hennessy, Sean; Yang, Wei; Dunn, Thomas; Weisman, A.R.; Oniyide, Oluwatosin; Agyekum, R.S.; Turner, Alexandra P.; Ittner, C.A.G.; Anderson, Brian J.; Wilson, F. Perry; Townsend, Raymond R.; Reilly, John P.; Giannini, H.M.; Cosgriff, Christopher V.; Jones, T.K.; Meyer, Nuala J.; Shashaty, Michael G. S.

doi:10.1007/s00134-022-06811-0

Cited by 56 publications

(42 citation statements)

References 49 publications

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“…Despite epidemiological data showing an association of AKI with beta-lactam administration, direct causality can be found only rarely. A possible increase in AKI related to the combination of antibiotics, for example, the most frequently used piperacillin and vancomycin, is not based on evidence of causality [ 86 ]. Surprisingly, data suggesting the protective role of a combination of piperacillin and vancomycin exist [ 87 , 88 ].…”

Section: Beta-lactam Toxicitymentioning

confidence: 99%

“…They bind with higher affinity to renal transporters mediating creatinine secretion and, consequently, serum creatinine levels increase. Thus, the association with AKI defined by creatinine levels should be called pseudotoxicity, rather than defined as a real toxic effect [ 86 ]. As already mentioned, using a single creatinine level in estimating GFR in a critically ill patient is not appropriate, and other approaches, such as measuring cystatin levels or four-hour creatinine clearance, should be prioritized [ 90 , 91 ].…”

Section: Beta-lactam Toxicitymentioning

confidence: 99%

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Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review

et al. 2023

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Beta-lactam antibiotics remain one of the most preferred groups of antibiotics in critical care due to their excellent safety profiles and their activity against a wide spectrum of pathogens. The cornerstone of appropriate therapy with beta-lactams is to achieve an adequate plasmatic concentration of a given antibiotic, which is derived primarily from the minimum inhibitory concentration (MIC) of the specific pathogen. In a critically ill patient, the plasmatic levels of drugs could be affected by many significant changes in the patient’s physiology, such as hypoalbuminemia, endothelial dysfunction with the leakage of intravascular fluid into interstitial space and acute kidney injury. Predicting antibiotic concentration from models based on non-critically ill populations may be misleading. Therapeutic drug monitoring (TDM) has been shown to be effective in achieving adequate concentrations of many drugs, including beta-lactam antibiotics. Reliable methods, such as high-performance liquid chromatography, provide the accurate testing of a wide range of beta-lactam antibiotics. Long turnaround times remain the main drawback limiting their widespread use, although progress has been made recently in the implementation of different novel methods of antibiotic testing. However, whether the TDM approach can effectively improve clinically relevant patient outcomes must be proved in future clinical trials.

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Section: Beta-lactam Toxicitymentioning

confidence: 99%

Section: Beta-lactam Toxicitymentioning

confidence: 99%

Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review

et al. 2023

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“…Notably, in animal models, piperacillin has been shown to impair tubular secretion of creatinine without causing tubular damage ( Pais et al, 2020 ). A recent prospective study in adults has shown that use piperacillin-tazobactam over cefepime is associated with higher rates AKI as defined by changes in serum creatinine but without concurrent changes in blood urea nitrogen or cystatin C ( Miano et al, 2022 ). Therefore, ideally these pediatric studies would include non-creatinine markers of kidney function such as cystatin C and kidney injury-specific urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to distinguish between pseudo-nephrotoxicity from impaired tubular secretion of creatinine and true kidney injury.…”

Section: Who Might Benefit From β-Lactam Precision Dosing?mentioning

confidence: 99%

β-lactam precision dosing in critically ill children: Current state and knowledge gaps

et al. 2022

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There has been emerging interest in implementing therapeutic drug monitoring and model-informed precision dosing of β-lactam antibiotics in critically ill patients, including children. Despite a position paper endorsed by multiple international societies that support these efforts in critically ill adults, implementation of β-lactam precision dosing has not been widely adopted. In this review, we highlight what is known about β-lactam antibiotic pharmacokinetics and pharmacodynamics in critically ill children. We also define the knowledge gaps that present barriers to acceptance and implementation of precision dosing of β-lactam antibiotics in critically ill children: a lack of consensus on which subpopulations would benefit most from precision dosing and the uncertainty of how precision dosing changes outcomes. We conclude with opportunities for further research to close these knowledge gaps.

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“…4 The mechanism of AKI in patients on VPT therapy is not well understood; proposed mechanisms include acute interstitial nephritis (AIN), acute tubular necrosis (ATN), pseudo-nephrotoxicity, and intratubular crystal obstruction. 1,5…”

Section: Introductionmentioning

confidence: 99%

Acute Kidney Injury Incidence With Bayesian Dosing Software Versus 2-Level First-Order Area Under the Curve–Based Dosing of Vancomycin With Piperacillin-Tazobactam

Bellamy

Covington

2023

Journal of Pharmacy Technology

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Background: Two methods of area under the curve (AUC) dosing are recommended in vancomycin consensus guidelines: first-order calculations utilizing 2 vancomycin concentrations or a Bayesian approach. It is unknown if there is a difference in acute kidney injury (AKI) between the 2 dosing strategies for patients receiving concomitant piperacillin-tazobactam and vancomycin (VPT). Objective: The objective of this study was to compare incidence of AKI in patients being administered VPT with first-order calculations versus model-informed precision dosing (MIPD)/Bayesian dosing. Methods: This was a single-center, retrospective, observational study at a community hospital. Patients who received VPT therapy for at least 48 hours were included. The primary outcome was overall incidence of AKI. Secondary outcomes included percentage target attainment with initial regimen, average serum creatinine increase, time to AKI, usable vancomycin levels, and need for temporary dialysis or intensive care unit admission. Results: There were 100 patients included (50 in the first-order group and 50 in the MIPD/Bayesian group). The overall incidence of AKI was lower in the MIPD/Bayesian group (12% vs 28%, P = 0.046). There was no difference in average serum creatinine increase, time to AKI, need for temporary dialysis, or intensive care unit admission. Patients in the MIPD/Bayesian group had a higher percentage of target attainment (46% vs 18%, P = 0.003) and usable vancomycin levels (98% vs 60%, P < 0.001). Conclusion and Relevance: In patients receiving VPT, model-informed precision dosing with Bayesian modeling resulted in a lower rate of AKI, higher target attainment, and more usable vancomycin levels compared with first-order AUC dosing. The small sample and retrospective nature of this study reinforces the need for additional data.

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Association of vancomycin plus piperacillin–tazobactam with early changes in creatinine versus cystatin C in critically ill adults: a prospective cohort study

Cited by 56 publications

References 49 publications

Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review

Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review

β-lactam precision dosing in critically ill children: Current state and knowledge gaps

Acute Kidney Injury Incidence With Bayesian Dosing Software Versus 2-Level First-Order Area Under the Curve–Based Dosing of Vancomycin With Piperacillin-Tazobactam

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