# Acute Cholecystitis Caused by Ceftriaxone Stones in an Adult

Authors: Christian D. Becker; Robert A. Fischer
Journal: Case Reports in Medicine
 (2009)

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## Abstract

Acute cholecystitis is a major health problem. There are multiple etiologies to be considered and early recognition of the condition is important to optimize management and outcome. We report the first case in the medical literature of symptomatic acute cholecystitis triggered by ceftriaxone-associated gallbladder sludge formation and, importantly, solid ceftriaxone gallstone formation in an adult patient with underlying mineral and pigment cholecystolithiasis, necessitating cholecystectomy. This case serves as a reminder for physicians to keep this uncommon cause of cholecystolithiasis and cholecystitis in mind in patients who receive prolonged ceftriaxone therapy. These patients should be cautioned to promptly report to their physicians any signs or symptoms of cholecystitis in order to ensure timely and appropriate evaluation.


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## Body

## 1. Background

Acute cholecystitis is a major health problem. There are multiple etiologies to be considered and early recognition of the condition is important to optimize management and outcome.


## 2. Case Report

A-68-year-old African-American male was admitted for 2 days of worsening right
upper quadrant abdominal pain. The pain was constant, noncolicky,
nonradiating, 6–8/10 in intensity, accompanied by nausea and vomiting with
attempted food intake. No fevers or chills were present.9
weeks prior to admission the patient underwent craniotomy for drainage of
multiple brain abscesses. Cultures were negative. Long-term empiric therapy
with high doses of ceftriaxone (2 gm i.v. q12 hours), caspofungin (50 mg i.v.
q24 hours), metronidazole (500 mg p.o. q8 hours), and corticosteroids was initiated
at that time.Physical
examination revealed marked right upper quadrant tenderness and a positive
Murphy’s sign. Laboratory data showed a normal white blood cell count of 5400/mm3,
hemoglobin of 10.3 g/dL, normal blood chemistry values except a blood glucose
of 157 mg/dL. The total bilirubin was normal at 0.2 mg/dL, the alkaline
phosphatase was slightly elevated at 177 IU/L. The transaminases were normal
(AST 21 IU/L, ALT 14 IU/L).A CT  scan revealed gallbladder wall thickening, pericholecystic
fluid, and multiple gallstones in the gallbladder.The
patient underwent cholecystectomy on the day of admission. The gallbladder
contained numerous green-yellow gallstones of various sizes (see Figure1),
which were soft and easily compressible.Figure 1
Surgical
specimen (gallbladder, with resection clips) showing a large number of greenish-brownish gallstones of various sizes and “crumbly” consistency.The
patient experienced an uncomplicated postoperative course.The
prolonged treatment with high doses of ceftriaxone and peculiar consistency of
the gallstones resulted in the clinical suspicion of ceftriaxone-associated
gallstones. Therefore, a gallstone sample was analyzed by high-pressure liquid
chromatography [1]. The
sample contained 70.4% minerals, 7.5% pigments, and 0.1% cholesterol as well as
significant amounts of ceftriaxone calcium salt (mean of 22%, with 3 separate measurements
of 20.97%, 23.43%, and 21.59%).


## 3. Discussion

Ceftriaxone
is 10–40% hepatically eliminated [2] and is known to induce reversible
precipitates of ceftriaxone calcium in the gallbladder [3].
Ultrasonographically, these precipitates resemble gallbladder sludge, but the
ultrasound-morphologic similarity to gallstones as well as the rapid
disappearance after discontinuation of ceftriaxone has resulted in the term
“ceftriaxone pseudolithiasis.”The
phenomena of ceftriaxone-associated sludge formation and ceftriaxone-associated
cholelithiasis are well documented in the pediatric literature and have resulted
in unnecessary cholecystectomies in pediatric patients. The incidence of
ceftriaxone sludge formation in patients treated with ceftriaxone ranges from
25% to 46%, but only a minority of these patients become symptomatic [4].A
Medline search with the terms (“ceftriaxone” AND (“acute
cholecystitis” OR “cholecystolithiasis”)) from 1980 to 2008 revealed
one report of ceftriaxone-associated cholecystolithiasis leading to acute
gallstone pancreatitis in a 42-year-old male [5], but no reports of
ceftriaxone-associated cholecystolithiasis with acute cholecystitis in adults.However,
there are several reports of coexisting cholecystolithiasis in patients with
ceftriaxone-associated gallbladder sludge formation. There are three mechanisms
by which a patient receiving ceftriaxone can develop acute cholecystitis:
ceftriaxone-associated sludge can trigger existing gallstones to become
symptomatic, ceftriaxone pseudolithiasis can transform into ceftriaxone
gallstones, or the patient can become symptomatic from preexisting
cholecystolithiasis unrelated to ceftriaxone therapy.Because
of the unusual appearance and consistency of the stones in our patient and the
analysis showing that ceftriaxone was incorporated into the stones in
significant amounts, we believe that ceftriaxone therapy was responsible for
the development of acute cholecystitis in our patient.


## 4. Conclusion

We
report the first case in the medical literature of symptomatic acute
cholecystitis triggered by ceftriaxone-associated gallbladder sludge formation
and, importantly, solid ceftriaxone gallstone formation in an adult patient
with underlying mineral and pigment cholecystolithiasis, necessitating
cholecystectomy.This
case serves as a reminder for physicians to keep this uncommon cause of
cholecystolithiasis and cholecystitis in mind in patients who receive prolonged
ceftriaxone therapy. These patients should be cautioned to promptly report to
their physicians any signs or symptoms of cholecystitis in order to ensure
timely and appropriate evaluation.



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*Source: 132452-2009-04-26.xml*