Case Presentation: This patient is a 74-year old male with CAD, HFpEF, HTN, Type 2 DM, CKD3, and obesity admitted for sepsis secondary to bilateral lower extremity purulent cellulitis, complicated by acute decompensated heart failure. He was started on cefepime 2 g twice daily and on vancomycin (vanco), dosed daily by level. After receiving only two doses of vanco 1g, the patient was found to have persistently elevated vanco levels > 100ug/mL complicated by acute kidney injury (AKI) (Cr 2.28;2.0-2.2) presumed due to vanco-induced nephrotoxicity. The patient’s AKI resolved and his clinical status improved, with no hemodialysis (HD), within five days of admission. However, vanco levels remained persistently elevated > 75ug/mL even nine days after initial vanco administration and remained persistently elevated post-discharge. Three-week levels were 62 ug/mL and one-month levels were still 29.9 ug/mL.
Discussion: Vanco was first approved by the FDA in 1958 and is the first-line treatment for methicillin-resistant Staph Aureus (MRSA) infections. It is notorious for being difficult to administer, especially in those with kidney disease. Recommendations to prevent AKI include monitoring drug levels, renal dosing, and withdrawing the drug as early as possible. There are 13 biopsy-proven cases of vanco-induced AKI in the literature. Most AKI’s lasted for three days to four weeks. Only one case report took a longer time (two months) for renal function to improve. ATN-induced cases were rarer (3/13) compared to AIN (8/13) or both (2/13). In all cases, either HD (in the case of acute tubular necrosis (ATN)) or steroids (in the case of acute interstitial nephritis (AIN) was required for the treatment of AKI.[1] This patient had ATN-induced AKI. To our knowledge, this is the first reported case of severe vanco-induced nephrotoxicity that resolved without steroids or HD. In addition, this patient’s vanco levels remained significantly elevated even after SCr levels returned to baseline, suggesting that this patient may have a polymorphism predisposing him to impaired vanco clearance. Further studies exploring the genetics of vanco clearance would be helpful in identifying patients with increased sensitivity. Finally, risk factors for vanco-induced AKI include high BMI, low eGFR, and the combination of vanco with piperacillin-tazobactam (OR, 3.40; 95% CI, 2.57 – 4.50), cefepime, or carbapenem (OR 2.68; 95% CI, 1.83 – 3.91), as in this patient. To address the limitations of using trough concentration as a proxy for measuring the actual AUC value, Bayesian computer software programs have been proposed to estimate the “true” vanco AUC value. Additionally, a number of new anti-MRSA drugs are in development, including novel dalbavancin, telavancin, oritavancin, ceftobiprole and iclaprim.
Conclusions: Vanco is the first-line for the treatment of hospital-acquired MRSA infections in the United States, but monitoring levels has been a complication of its use. This is a unique case of a patient with severe, persistently elevated vanco levels with transient AKI not requiring HD. This patient may have a polymorphism, thus prompting further studies to identify patients with increased predisposition to vanco-induced nephrotoxicity. Risk factors for AKI should be considered, including obesity and concurrent use of other antibiotics. As new measurements and treatments become more widely available, patients with genetic or comorbid risk factors should be offered alternative agents to vanco before beginning treatment.