Multiple drugs

Abstract

Various toxicities: case report A 55-year-old man developed acute kidney injury (AKI) during treatment with carfilzomib and secondary to vancomycin intoxication following overdose. In addition, he developed encephalopathy during treatment with lenalidomide and cefepime. Further, he did not respond to cefazolin for the treatment of Klebsiella pneumoniae infection [routes not stated; not all dosages stated]. The man, whose medical history was significant for a previously treated plasmacytoma, was hospitalised due to its recurrence. On day 8 of admission, he developed pyelonephritis with bacteraemia; hence, he started receiving ceftazidime. Thereafter, his body temperature decreased on days 9 and 10; however, it rose on day 11. Therefore, he started receiving cefepime 4g daily. Subsequently, the causative organism was identified as Klebsiella pneumoniae sensitive to cefazolin; therefore, he started receiving cefazolin on day 16. However, his body temperature rose again on day 21 and did not decrease in spite of repeated escalation of antibiotics, including cefepime 4g daily. On the same day, the results of further analyses raised suspicions for a urinary tract infection secondary to Enterococcus faecium; hence, he started receiving vancomycin on day 24, in addition to the ongoing cefepime. Subsequently, follow-up analyses for his underlying condition revealed progression of plasmacytoma. Therefore, on day 25, he started receiving carfilzomib, lenalidomide and dexamethasone. However, the following day (day 26) he developed AKI, and on day 29, the AKI aggravated, with high serum levels of vancomycin. Therefore, the man’s treatment with vancomycin was stopped on day 29. Cefepime was also discontinued on the same day, and he started receiving crystalloid. On day 30, he developed a consciousness disorder. He was referred to the nephrology department. Analyses of his vital signs revealed the following: BP 100/62 mmHg, HR 80 bpm, temperature 37.2°C, RR 16 bpm and oxygen saturation 98%. His Glasgow Coma Scale was E4V4M5. Physical examination showed abdominal distention. Laboratory analyses revealed pancytopenia, hypoalbuminaemia, renal dysfunction, high urinary levels of β2-microglobulin (53 948 μg/L) and N-acetylbeta-D-glucosaminidase (141.4 U/L), and high serum levels of vancomycin (47.1 μg/mL). Based on these findings, and after ruling out all other possible aetiologies, it was suspected that his AKI was due to vancomycin intoxication and the kidney myeloma. At the same time, it was also suspected that his consciousness disorder developed secondary to cefepime-induced encephalopathy, since he had received a large amount of cefepime in the background of renal dysfunction. Electroencephalography (EEG) revealed triphasic waves but not epileptic waves, confirming drug-induced encephalopathy. However, in spite of discontinuing vancomycin and cefepime, his serum levels of vancomycin did not decrease, and his consciousness did not improve. Therefore, on day 32, he started undergoing online haemodiafiltration. Ascites examination demonstrated accumulation of vancomycin and cefepime into massive ascites. Therefore, abdominal drainage was performed along with online haemodiafiltration. Thereafter, his serum levels of vancomycin decreased, and his consciousness recovered (day 37). However, his underlying plasmacytoma progressed; therefore, he started receiving bortezomib, doxorubicin and dexamethasone on day 40. However, his renal dysfunction and low urine output persisted, leading to hypoxia secondary to pleural effusion, which did not respond to unspecified diuretics. Therefore, he started undergoing weekly haemodialysis. However, on day 43, he developed cytomegalovirus viraemia; therefore, he started receiving ganciclovir, which was continued until resolution of the infection. The development of AKI was thus attributed to vancomycin intoxication following overdose, with carfilzomib being a contributing factor, while the encephalopathy was attributed to cefepime, with lenalidomide being a contributing factor [not all times to reactions onsets clearly stated].