A 41 y.o. female patient with history of CKD presents to the emergency room on July 11, 2022 with complaints of four days of RLQ abdominal pain and constipation. She also reports nausea, vomiting and decreased PO intake. Her initial vitals are as follows: T-99.5, BP- 186/100, P- 116, RR-20. Her initial labs drawn at 1251 revealed the following: WBC- 22.14, Hgb- 10.8, Neutrophil %- 87.8. Her BMP reflected the creatinine to be 2.25 and EGFR 27. Please note that the her baseline creatinine ran in the 2.22 range and her EGFR was around 28.
An ultrasound of the abdomen was completed and was interpreted as showing cholelithiasis with gallbladder thickening and a dilated common bile duct. The patient was started on 4.5g of Zosyn at 200ml/hr at 1550. A surgical consultation was completed at 1606. The surgeon recommended a CT scan of the abdomen and pelvis along with a sepsis workup. Please note that blood cultures were obtained after the Zosyn was started. Blood cultures had no growth. A lactic acid drawn at 1637 was normal at 1.2.
The surgeon did not feel acute surgical intervention was indicated at that time. However, she did recommend broad spectrum antibiotics to include MRSA and GNR anaerobes. The CT was competed at 1731 and was interpreted as showing evidence of cholelithiasis with gallbladder wall thickening, distension and adjacent fat stranding concerning for superimposed acute cholecystitis.
The patient was seen by the admitting hospitalist at 1725. Given the recommendation for broad spectrum antibiotic coverage, the hospitalist ordered 2000 mg IV vancomycin every Q12H. The pharmacist signed off on the order. The Zosyn was alos ordered at 4.5 mg at a rate of 25ml/hr Q8H.
The vancomycin was started at 2038 followed by another dose of Zosyn at 2254. The Zosyn was given again at 0458 on July 12, 2022. The labs drawn at 0350 on July 12th showed a decrease of the WBC to 14.92. The Hgb was 9.9 and neutrophil percentage was 84. The BMP revealed an increase of the Creatinine to 3.47 and decrease of the EFGR to 16.
The patient was seen by the Hospitalist at 0900 on July 12th. His plan was to hold the Vancomycin. At that point, one 2000mg dose had been given. He also ordered a routine consult with nephrology. The surgeon saw the patient at 1146 and continued with her plan of non-operative management with bowel rest and antibiotics. Zosyn was given at 1427 and 2116. It was also given at 0504 on July 13th.
The July 13th labs drawn at 0503 showed a WBC of 9.91 and neutrophil percentage of 80.3%. The creatinine increased to 5.18 and the EGFR was 10.
The surgeon saw the patient at 0914 and noted that nephrotoxic agents were to be avoided. The nephrology consultation was competed at 1223. The nephrologist noted AKI on CKD. He further charted that the AKI was likely secondary to IVVD and possible medication induced AIN from simultaneous use of vancomycin and PiP/Tazo. He also noted that since admission that the patient had received multiple doses of PiP/Tazo and Vancomycin as well as IVF of NaCL and LR. She continued on LR at 125 ml/hr. Finally, he charted that the patient had been on an NPO diet since admission but had advanced that morning to clear liquids. His plan included obtaining a renal US and that the patient was to avoid nephrotoxic medications. As such, the Zosyn was discontinued and switched to Cefepime and Flagyl.
The renal ultrasound was completed that same day. The right kidney measured at 4.9 x 10.8 x 4.9 cm with increased cortical echogenicity. There was no hydronephrosis, focal renal mass lesion or shadowing stone. The left kidney measured at 6.2 x 12.5 x 4.1 cm with normal cortical echogenicity. However, the radiologist’s impression states bilateral echogenic kidneys which may reflect medical renal disease.
The creatinine continued to increase thereafter as follows: 7/14- 6.12, 7/15- 6.82, 7/16- 7.24, 7/17- 7.29. Hemodialysis was started on July 15th. The patient was also transitioned to PO antibiotics on that date. However, it only ran for 13 minutes as the patient had difficulties and discomfort at the venous site. In fact the RIJ Udall was not working on July 16th and leaking. She was then transferred to the downtown hospital location for IR to place a tunneled catheter. It was subsequently placed on 7/18. The nephrology note on July 17th reflects an assessment of acute kidney injury from questionable vancomycin nephrotoxicity.
The patient’s creatinine from the July 18 1622 draw was 5.86 with an EGFR of 9. She continued with inpatient hemodialysis until her discharge on July 25th. Her creatinine on that date was 4.67 and her EGFR was 11.
Following her discharge, the patient has required ongoing dialysis three days a week with each session lasting 4.5 hours. Her labs in April 2023 showed KT/V1 .28, urea reduction ratio 72%, Hgb 11.9, albumin 3.8, calcium 9.2, phosphorus 3.4 and intact PTH 3427. Her creatinine in July 2023 was 4.79. Her treating nephrologist has noted that a kidney biopsy has not been done due to the patient’s morbid obesity and body habitus. The patient is also not a candidate for kidney transplantation due to her morbid obesity.
I am looking for an opinion related to the cause of the patient's kidney deterioration. As stated, her creatinine and EGFR were 2.2 and 28 respectively before this hospital admission. In other words, was the insult to the kidneys that led to the advancement of her disease more likely than not due to the administration of vancomycin and PiP/Tazo? Also, a nephrologist was not consulted before vanco was added to the PiP/Tazo. I am interested in how a nephrologist should address the proposed vanco/PiP/Tazo combination had a consult been requested regarding antibiotic choice on July 11th.
Files:
Q: Ct scan with contrast? Urine studies? Other medications? Did Nephro review sediment?
A: CT was without contrast. Urine drawn on 7/13 showed creatinine at 209, sodium 26, albumin 66.1, Pr. 185. Urinalysis on 7/13- no bacteria, WBC 7, specific gravity 1.0. No Sed rate obtained. Also, she weighed 341 lb.
Do you believe there might have been medical error?
Renal toxicity has been found with the combination of vancomycin and pip/tazo, but it is very controversial - other studies suggest it does not increase the risk of renal failure. Vancomycin levels should be monitored if continuing after the first dose in patients with advanced renal failure - we check a trough level before the next dose to ensure the level is therapeutic but not too high. I did not see a weight in the description, but based on the comment that the patient is morbidly obese, the first dose may have been appropriate (usually something like 15-20mg/kg as an initial vanc dose). Since no further doses were given, no need for checking levels. The pip/tazo dose given was high. Typically 4.5g is only given in certain patients with pneumonia with normal renal function (and that is given every 6 hours, not every 8 as it was written above). The correct dose would usually be 2.25g q6 hours according to the drug's package dosing chart. However, there is some argument to be made that a different dose was appropriate based on the patient's weight, again depending on the actual weight of the patient, and that perhaps a higher dose was justified for some reason. No reason to wait for a nephrologist opinion before giving these antibiotics in general.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
See above. Likely justifiable use of antibiotics. Most likely this patient required dialysis due to her sepsis and volume depletion causing AKI. Her baseline CKD stage 4 makes an AKI of any type likely to result in the need for dialysis.
What makes you a good expert for this case?
I am a full time practicing nephrologist with over 10 years in general nehprology and interventional nephrology. I have thousands of visits with hospitalized patients each year, any many similar to this case. I have been providing expert witness services for one year, working with both plaintiff and defense. I have a Florida expert medical witness certificate.
How often do you encounter cases similar to this one in your practice?
Very often. This case covers many topics that I see on a regular basis in my practice.
Do you believe there might have been medical error?
I see no evidence of any medical error in this case. The use of Vancomycin and Zosyn is within standard of care.
Do you believe there might have been causation (i.e. the medical error resulted in an injury)?
Simultaneous use of vancomycin and piperacillin-tazobactam is within standard of care. While there may have been vancomycin toxicity in this case (and this remains uncertain), the dosing seems appropriate for the patient's size. The rapid increase in creatinine makes Zosyn AIN unlikely as you would expect this to start after a few days of exposure and THEN worsen slowly thereafter. The dosing of the Zosyn appears appropriate for the stated GFR.. I do NOT see a medical error contributing to the injury.
What makes you a good expert for this case?
This is a bread and butter case that can be handled by most nephrologists who see AKI and have a basic understanding of vancomycin related toxicity and the controversies surrounding piperacillin-tazobactam "nephrotoxicity." I use quotes because whether piperacillin tazobactam is uniquely toxic is under debate (including at the most recent ASN). I've practiced at a large single specialty nephrology practice for the past ten years. We cover a tertiary care center that sees many surgical patients like the one described above. I've been voted Top Doc in Delaware multiple times, including most recently in 2023 by Delaware Today. This is voted by peers in the state.
How often do you encounter cases similar to this one in your practice?
Frequently. I see consults like this on a daily basis.
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