A 62-year-old male patient, weighing 85 kg, was initially admitted for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia complicated by acute respiratory distress syndrome, warranting mechanical ventilation. Initial kidney function was normal (plasma creatinine, 70 μmol/L; estimated glomerular filtration rate, 94 ml/min). On weening from mechanical ventilation, Enterococcus faecium together with Pseudomonas aeruginosa pneumonia prompted treatment with piperacillin-tazobactam therapy and vancomycin (2500 mg, 2 daily i.v. administrations). Thirty-six hours following antibiotic therapy initiation, the patient developed abrupt oliguric stage 3 acute kidney injury with a peak plasma creatinine level of 570 μmol/L. On admission, the patient was mildly hypertensive, with an otherwise unremarkable clinical assessment. Kidney ultrasound examination was normal. Urine investigations were consistent with tubular injury by disclosing mild proteinuria (urine protein-to-creatinine ratio, 0.1 g/mmol) composed of albuminuria at low levels (urine albumin-to-creatinine ratio, 34 mg/mmol) and elevated retinol-binding protein levels: 3.29 mg/L (normal range, <0.01 mg/L). The vancomycin trough level was found to be greatly elevated (41 mg/L). The day following his admission, urinalysis was ordered. Microscopic examination revealed vitreous casts on light microscopy, devoid of refringence after polarization. A pellet of urine was spread on a slide, and immunostaining performed with a specific antivancomycin antibody (Abbot 6E-4421; 1:1000) confirmed the presence of vancomycin casts, a finding further substantiated by infrared spectrum imaging (Figure 1 and Supplementary Figures S1 and S2). Immunostaining was negative in control urine samples containing proteins or crystals. Vancomycin therapy was discontinued, and the patient fully recovered his baseline kidney function within 10 days. Combined piperacillin-tazobactam and vancomycin may have enhanced the risk for acute kidney injury. Recent studies have evidenced vancomycin cast intratubular formation on kidney pathology examination in the setting of high trough levels. Yet, as vancomycin-associated tubular injury typically resolves with supportive care, urinalysis combined with specific immunostaining may offer a welcome noninvasive alternative diagnostic tool to kidney biopsy.