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Emphysematous pyelonephritis (EPN) is a rare condition that typically occurs in patients with diabetes mellitus, urinary tract obstruction, or immunosuppression such as solid organ transplant recipients. It has high mortality and frequently requires nephrectomy to achieve cure, although percutaneous drainage has been reported to be successful in some patients. We report a renal transplant recipient with underlying diabetes mellitus who developed iatrogenic EPN. The patient initially presented with dyspnea and was admitted for cardiac evaluation. There was no evidence of urinary tract infection at the time of admission. The patient developed high-grade fever 3 days after admission. Despite intravenous (IV) antibiotic therapy, the patient developed acute renal failure requiring hemodialysis. Studies revealed Klebsiella bacteremia and EPN. We believe that urinary tract infection was precipitated by urinary bladder catheterization performed on the day of admission. Despite 2 weeks of IV antibiotic therapy, infection persisted with progressive extension of gas into the perinephric space on repeat imaging. The patient underwent a transplant nephrectomy with subsequent clinical recovery. This case illustrates that antibiotics alone are often inadequate to cure and preserve renal function in EPN despite immediate therapy. Furthermore, this patient underscores the risk of serious infection precipitated by urinary bladder catheterization in immunocompromised patients.