79 year old female who had peripheral vascular issues particularly with her left lower extremity. Had a fempop in July of 2022. She was seen by her vascular surgeon in Florida in December of 2022 who recommended to go to ER to receive antibiotics for potential cellulitis to the area of concern. Upon arrival they ruled out DVT and ultrasound revealed minor seroma and fluid collection. There were no signs of sepsis or neurological issues. Should be noted that she has a history of stage 3 kidney disease, cad, hypertension. Hospital note on day 3:
"followed Dr. *** for stage IIIb/IV CKD with baseline creatinine 1.77”
She was immediately started on cefepime and vancomycin. She was admitted with an initial creatinine level of 1.11 with a GFR 57. Nephrology notated that this was "better than it normally is" and saw no issue with her receiving the medication that she was. She was receiving cefepime every 8 hours for approximately 12 days.
They were attempting to set up for discharge approximately 7 days later with a peripheral angiogram and TEE. However, family was notifying the providers that she was slowly becoming more altered. 5 days later, PC was difficult to arouse multiple times throughout the day. They were attempting to do physical therapy but she was unable to weakness and AMS. They ordered a CT of her head which showed no acute illness. Multiple notations about using caution with contrast during CTs due to baseline CKD.
EEG was done and was consistent with metabolic encephalopathy. A geriatric consult was placed admit day +14 and it was around this time that the cefepime was finally discontinued.
They did not perform an MRI until admit +20 which showed ischemic changes. MRI was delayed due delays in getting EEG started and clearance for AKI and dental hardware in mouth? No clear notes on this.
PC was intubated and on continuous anti-seizure medication. Due to her lack of her overall progress, the facility wish to transfer her to long-term ICU care to attempt to wean her off the ventilator. This took multiple days to make happen, however was eventually D/C to LTICU.
PC did not improve and passed away on Jan 2023.
CREATININE: started at 1.11 however began to climb for multiple days, peaking at 3.15, 3.3 and 2.8 on consecutive days.
Infectious disease and internal medicine were following the PC and there is concern that the Cefepime was contraindicated for multiple reasons. We have full records for reference if this appears to the contributing factor in PC's rapid decline.
I have included some excerpts from the chart below:
(These are from about 2 weeks post admission)
Encephalopathy could be metabolic (hypoxia from fluid overload and respiratory failure) vs toxic (cefepime could be contributing?).
EEG reading seizure and started on Keppra and valproate by neurologist.
Renal function had been worsening for four days in a row, today with minimal change but there has been recorded improvement in urine output. Patient has been off antibiotics. Upon reviewing providers notes, vital signs, lab results, and performing physical exam, I found no evidence of different infectious process. Leukocytosis possibly impacted by systemic steroid and kidney injury (ATN?).
Daughter had questions for me today that I answered to the best of my ability. She had specific questions about the use of cefepime and whether a different antibiotic would have been preferred. I answered that the initial concern was a potentially serious infection on deep tissue (endovascular graft), situation that until patient required transfer to ICU and intubation, was still under evaluation by Vascular Surgery, and cefepime would provide effective treatment for organisms of concern to be involved in this type of infections. That includes Pseudomonas (not covered by ceftriaxone or ertapenem) and AmpC producer organisms (not covered by ceftriaxone). I think the cefepime is a possible cause or contributor to the patient's encephalopathy, but it is difficult to tell with certainty; overall the neurotoxicity seems to be considered a rare side effect from the cefepime when dosed within appropriate range. Looking at
the daily trend in her creatinine/creatinine clearance during this hospitalization, the dose of cefepime seemed appropriate/in range for the targeted infectious process and suspected organism(s).
Assessment and Plan:
Patient is a 79-year-old female with a past medical history as mentioned above including atrial fibrillation on Xarelto, presenting with left lower extremity cellulitis. Patient with progressive altered mental status during this admission. Patient had EEG which was concerning for nonconvulsive status epilepticus. There was some question of this was metabolic and toxic associated provoking her situation. Patient had been receiving cefepime for cellulitis. This has since been discontinued. Requiring multiple antiepileptic regimen and propofol. Propofol has been off now since Thursday. No clear electrographic seizure appreciated. At times triphasic waves with increased frequency seen. Consistent with metabolic encephalopathy. Patient has had a slow improvement in renal function over the last several days. She also seems to be getting slightly more reactive each day but very slow progression. I discussed with patient's husband that she may not make a full recovery, and that time would only tell. Defer to them on how aggressive they would like to be with her recovery.
Recommendations:
Continue Keppra 1500 mg IV every 12 hours, currently weaning off Vimpat. Will receive about 50 mg twice daily today, followed by 50 mg daily x2 days followed by discontinuation. Depakote has been discontinued.
Defer to infectious disease regarding increasing leukocytosis, defer to nephrology regarding renal impairment. Both seem to be improving.
Repeat EEG completed Monday was consistent with a severe encephalopathy. Overall
improvement as there was no clear triphasic waves appreciated. MRI brain without contrast reviewed. Very small punctate infarct which is felt to be an incidental
finding. No other recommendations from neurology at this point. I will plan to sign off today but certainly available should any other neurological questions or concerns arise.
Files:
No questions yet!
Do you believe there might have been medical error?
Dose of cefepime was appropriate for the significant infection and the neurotoxicity from cefepime is very rare. Patient had other comorbidities to explain her worsening clinical syndrome and mental status changes
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
You cannot say cefepime caused her altered mental status without measuring cefepime levels in CSF. Patient had also other risk factors to have worsening renal failure which may cause per se metabolic encephalopathy
What makes you a good expert for this case?
I see these patients every day with cefepime, and i practice ID in high-complex cases for the last 20 years
How often do you encounter cases similar to this one in your practice?
I see these cases on a daily basis
Do you believe there might have been medical error?
While cefepime may lower the seizure threshold and predispose to encephalopathy and non-convulsive status epilepticus, the choice of cefepime in this case seems to have been appropriate, and, per the given text, the dose was correct. The excerpts also contain a thoughtful rationale for why this antibiotic was chosen, which seems reasonable. It should be noted that other antibiotics may also lower the seizure threshold. I think an argument for medical error could be made if the cefepime dose was too high, but that does not seem to have been the case.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
As stated above, I do not see evidence of a medical error in the given text. Furthermore, cefepime-induced encephalopathy typically resolves after cessation of the drug, so there may have been other factors that contributed to her lack of improvement and eventual death.
What makes you a good expert for this case?
I am a practicing infectious diseases physician with over 10 years of experience caring for inpatients with severe infections, including critically ill patients admitted to the ICU. I have prescribed cefepime thousands of times in these settings, and I have personally cared for patients with presumed neurologic toxicity from cefepime and other antibiotics.
How often do you encounter cases similar to this one in your practice?
I encounter cases similar to this patient's initial presentation at least once per week.
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