Editing Vancomycin (section)

====Nephrotoxicity====
The extent of nephrotoxicity for vancomycin remains controversial.<ref name="pmid6219616-2"/> In 1980s, vancomycin with a purity >&nbsp;90% was available, and kidney toxicity defined by an increase in serum creatinine of at least 0.5&nbsp;mg/dL occurred in only about 5% of patients.<ref name="pmid6219616-2">{{cite journal | vauthors = Farber BF, Moellering RC Jr | title = Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. | journal = Antimicrob Agents Chemother | volume = 1 | pages = 138–41 | date = 1983 | issue = 1 | doi = 10.1128/AAC.23.1.138 | pmid = 6219616 | pmc = 184631 }}</ref> But dosing guidelines from the 1980s until 2008 recommended vancomycin trough concentrations between 5 and 15&nbsp;μg/mL.<ref name="Rybak 2009 p.">{{cite journal | vauthors = Rybak MJ, Lomaestro BM, Rotschafer JC, et al. | title = Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. | journal = Clin Infect Dis | volume = 49 |  pages = 325–7 | date = 2009 | issue = 3 | doi = 10.1086/600877 | pmid = 19569969 | s2cid = 32585259 | doi-access = free }}</ref> Concern for treatment failures prompted recommendations for higher dosing (troughs 15 to 20 μg/mL) for serious infection, and acute kidney injury (AKI) rates attributable to the vancomycin increased.<ref name="Pais 2020 p.">{{cite journal | vauthors = Pais GM, Liu J, Zepcan S, Avedissian SN, Rhodes NJ, Downes KJ, Moorthy GS, Scheetz MH | title = Vancomycin-Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention | journal = Pharmacotherapy | volume = 40 | issue = 5 | pages = 438–454 | date = 2020 | doi = 10.1002/phar.2388 | pmid = 32239518 | pmc = 7331087 }}</ref>

Importantly, the risk of AKI increases with co-administration of other known nephrotoxins, in particular aminoglycosides. Furthermore, the sort of infections treated with vancomycin may also cause AKI, and sepsis is the most common cause of AKI in critically ill patients. Finally, studies in humans are mainly associations studies, where the cause of AKI is usually multifacotorial.<ref>{{cite journal | url=https://link.springer.com/article/10.1007/s00134-017-4799-8 | doi=10.1007/s00134-017-4799-8 | title=Diagnostic work-up and specific causes of acute kidney injury | date=2017 | journal=Intensive Care Medicine | volume=43 | issue=6 | pages=829–840 | pmid=28444409 | vauthors = Darmon M, Ostermann M, Cerda J, Dimopoulos MA, Forni L, Hoste E, Legrand M, Lerolle N, Rondeau E, Schneider A, Souweine B, Schetz M }}</ref><ref>{{cite journal | doi=10.3389/fmed.2021.678434 | doi-access=free | title=Clinical Characteristics and Risk Factors Associated with Acute Kidney Injury Inpatient with Exertional Heatstroke: An over 10-Year Intensive Care Survey | date=2021 | journal=Frontiers in Medicine | volume=8 | pmid=34095181 | pmc=8170299 | vauthors = Wu M, Wang C, Liu Z, Zhong L, Yu B, Cheng B, Liu Z }}</ref><ref>{{cite journal | doi=10.1007/s00134-021-06454-7 | title=Acute kidney injury in the critically ill: An updated review on pathophysiology and management | date=2021 | journal=Intensive Care Medicine | volume=47 | issue=8 | pages=835–850 | pmid=34213593 | vauthors = Pickkers P, Darmon M, Hoste E, Joannidis M, Legrand M, Ostermann M, Prowle JR, Schneider A, Schetz M | pmc=8249842 }}</ref><ref>{{cite journal | doi=10.1186/s13613-024-01360-9 | doi-access=free | title=Biomarkers in acute kidney injury | date=2024 | journal=Annals of Intensive Care | volume=14 | issue=1 | page=145 | pmid=39279017 | pmc=11402890 | vauthors = Ostermann M, Legrand M, Meersch M, Srisawat N, Zarbock A, Kellum JA }}</ref>

Animal studies have demonstrated that higher doses and longer duration of vancomycin exposure correlates with increased histopathologic damage and elevations in urinary biomarkers of AKI.37-38<ref name="Fuchs 2012 p.">{{cite journal | vauthors = Fuchs TC, Frick K, Emde B, Czasch S, von Landenberg F, Hewitt P | title = Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials.  | journal = Toxicol Pathol | volume = 40 | pages = 1031–48 | date = 2012  | issue = 7 | doi = 10.1177/0192623312444618 | pmid = 22581810 | s2cid = 45358082 }}</ref> Damage is most prevalent at the proximal tubule, which is further supported by urinary biomarkers, such as kidney injury molecule-1 (KIM-1), clusterin, and osteopontin (OPN).<ref name="Pais 2019 p.">{{cite journal | vauthors = Pais GM, Avedissian SN, ODonnell JN et al.  | title = Comparative performance of urinary biomarkers for vancomycin-induced kidney injury according to timeline of injury. | journal = Antimicrob Agents Chemother | year = 2019 | volume = 63 | issue = 7 | pages = e00079–19 | doi = 10.1128/AAC.00079-19 | pmid = 30988153 | pmc = 6591602 }}</ref> In humans, insulin-like growth factor binding protein 7 (IGFBP7) as part of the nephrocheck test.<ref name="Ostermann 2018 p.">{{cite journal | vauthors = Ostermann M, McCullough PA, Forni LG | title = Kinetics of Urinary Cell Cycle Arrest Markers for Acute Kidney Injury Following Exposure to Potential Renal Insults. | journal = Crit Care Med | volume = 46 | issue = 3 | pages = 375–383 | date = 2018 | doi = 10.1097/CCM.0000000000002847 | pmid = 29189343 | pmc = 5821475 }}</ref>

The mechanisms underlying the pathogenesis of vancomycin nephrotoxicity are multifactorial but include interstitial nephritis, tubular injury due to oxidative stress, and cast formation.<ref name="Pais 2020 p."/>

[[Therapeutic drug monitoring]] can be used during vancomycin therapy to minimize the risk of nephrotoxicity associated with excessive drug exposure. Immunoassays are commonly utilized for measuring vancomycin levels.<ref name="pmid38304144"/>

In children, concomitant administration of vancomycin and [[piperacillin/tazobactam]] has been associated with an elevated incidence of AKI relative to other antibiotic regimens.<ref name="pmid38279799">{{cite journal |vauthors=Zhang M, Huang L, Zhu Y, Zeng L, Jia ZJ, Cheng G, Li H, Zhang L |title=Epidemiology of Vancomycin in Combination With Piperacillin/Tazobactam-Associated Acute Kidney Injury in Children: A Systematic Review and Meta-analysis |journal=Ann Pharmacother |volume= 58|pages=1034–1044 |date=January 2024 |issue=10 |pmid=38279799 |doi=10.1177/10600280231220379 |s2cid=267300725 |url=}}</ref>