Ceftriaxone-induced Cholelithiasis

Lopez, Alvaro J.; O’Keefe, Paul; Morrissey, Marilynn; Pickleman, Jack

doi:10.7326/0003-4819-115-9-712

Cited by 61 publications

(30 citation statements)

References 10 publications

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“…This patient was managed conservatively, her symptoms resolved, and the gallstones dissolved spontaneously. Other reported complications of biliary pseudolithiasis are choledocholithiasis [26,32] and gallstone pancreatitis [15,16]. The gallbladders of the patients with gallstone pancreatitis showed histology consistent with chronic cholecystitis [15,16].…”

Section: Discussionmentioning

confidence: 95%

Acute necrotizing cholecystitis: a rare complication of ceftriaxone-associated pseudolithiasis

2006

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A 16-year-old male patient (59 kg) who presented to his primary care physician with a 3 week history of lethargy and myalgias. His physical examination was notable for a 5-cm bullseye lesion on his right foot, which was thought to be a spider bite. This resolved without treatment after 1 week. He developed a similar lesion on his left forearm, which also resolved on its own after 1 week. Four weeks after his symptoms began, he presented to our institution with a headache, jaw stiffness, and left-sided facial weakness (Bell's Palsy). He had a white blood cell count of 32,000 (normal 4,000-10,000). Lyme titers were positive. A lumbar puncture was performed and he was diagnosed with Lyme meningitis. He was treated with ceftriaxone 2 g intravenously twice a day for 4 weeks.The patient developed right upper quadrant pain 1 week after completing his treatment. The pain was intermittent and gradually became more severe over the next 2 weeks. He was seen again at our institution and an abdominal ultrasound was performed. It showed multiple gallstones with one gallstone in the gallbladder neck and mild gallbladder wall thickening (4 mm). There was no pericholecystic fluid and the common bile duct appeared normal. Due to his persistent and worsening symptoms, he underwent a laparoscopic cholecystectomy. He had a significant amount of inflammation around the gallbladder with indiscernible anatomy, and thus we converted to an open procedure.The pathological analysis showed acute necrotizing cholecystitis with surface erosions. The stone analysis by polarization microscopy and infrared spectroscopy revealed that the stone composition was 100% ceftriaxone (Laboratory for Stone Research, Newton, MA, USA). DiscussionCeftriaxone is a parenteral broad-spectrum, semi-synthetic third generation cephalosporin. A b-lactam antibiotic, it exerts its antibacterial activity through the inhibition of bacterial cell-wall synthesis. Its spectrum of activity includes many gram-positive aerobic bacteria, gram-negative aerobic bacteria and some anerobes. It is resistant to degradation by most bacterial b-lactamases [6]. Ceftriaxone's pharmacokinetic properties are nonlinear and all basic pharmacokinetic parameters (e.g. absorption and distribution), with the exception of the elimination half-life, are dose dependent. Its long halflife of elimination (i.e. 5.4 -10.9 h) allows for once or twice daily dosing.Although it is largely excreted in the urine, 10-40% is excreted unmetabolized in bile [5,7,17,22,29]. It is reversibly bound to albumin, and the binding decreases with the increase in concentration, e.g. from 95% binding at plasma concentrations less than 100 mg/l to 85% binding at 300 mg/l [17]. Due to the lower albumin content in interstitial fluid, the percentage of free drug in interstitial fluid is correspondingly higher than in plasma. As a result, the levels of ceftriaxone in the bile is 20-150 times greater than in serum [25]. As an anion, it binds to calcium and forms an insoluble calcium-ceftriaxone salt in a 1:1 molar ratio that is...

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Section: Discussionmentioning

confidence: 95%

Acute necrotizing cholecystitis: a rare complication of ceftriaxone-associated pseudolithiasis

2006

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“…At the 21 st day of antibiotic course the patient developed gallbladder microlithiasis, transient pancreatitis and acute cholecystitis requiring mandatory surgery consisting of laparoscopic cholecystectomy (unpublished data). A Medline search from the last four decades revealed only three reports of ceftriaxoneassociated gallbladder lithiasis leading to acute pancreatitis in adults 11,13,21 . Furthermore, only few cases of acute cholecystitis caused by ceftriaxone were reported in adults 22 .…”

Section: ■ Discussionmentioning

confidence: 99%

“…Likewise, when complains are present the general belief, even in adult's patients, is that the diagnosis of pseudolithiasis (sometimes denominated as sediment, sludge, precipitate) outlines a transient situation which disappears when the drug is discontinued [23][24][25][26] . However, a careful revision of the medical literature has showed a high incidence of symptomatology, ranging from 22% to 100% of the cases 7,10,11,12,21,22,27,28 . Ettestad et al 29 described 25 patients with Lyme disease diagnosis treated with ceftriaxone, of whom 14 underwent surgery with histopathological evidence of cholecystitis and 172 were diagnosed with biliary calculi.…”

Section: Long-term Therapy With Intravenousmentioning

confidence: 99%

“…It is noteworthy that microlithiasis formation in the gallbladder resulting from the use of ceftriaxone associated with serious adverse events is generally neglected, especially in adult population. In the medical literature, there are few but worrisome reports of acute biliary pancreatitis, acute cholecystitis including necrotizing type and choledocholithiasis followed by cholangitis during long-term ceftriaxone therapy [9][10][11][12][13] . The authors performed a translational study in an original rabbit model, aiming to study the reliable incidence of and cholecystitis due to intravenous ceftriaxone use, seldom described in the medical literature.…”

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confidence: 99%

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Cholecystectomy during ceftriaxone therapy. A translational study with a new rabbit model

Vasconcellos

Cozer²,

Diniz³

et al. 2017

Acta Cir. Bras.

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Purpose: To evaluate the actual incidence of both microlithiasis and acute cholecystitis during treatment with intravenous ceftriaxone in a new rabbit model. Methods: New Zealand rabbits were treated with intravenous ceftriaxone or saline for 21 days. Ultrasound monitoring of the gallbladder was performed every seven days until the 21 st day when histopathology, immunohistochemistry for proliferating cell nuclear antigen (PCNA), pro-caspase-3 and CD68, liver enzyme biochemistry, and chromatography analysis of the bile and sediments were also performed. Results: All animals treated with ceftriaxone developed acute cholecystitis, confirmed by histopathology (P<0.05) and biliary microlithiasis, except one that exhibited sediment precipitation. In the group treated with ceftriaxone there was an increase in pro-caspase-3, gammaglutamyl transpeptidase concentration, PCNA expression and in the number of cells positive for anti-CD68 (P<0.05). In the ceftriaxone group, the cholesterol and lecithin concentrations increased in the bile and a high concentration of ceftriaxone was found in the microlithiasis. Conclusion: Ceftriaxone administered intravenously at therapeutic doses causes a high predisposition for lithogenic bile formation and the development of acute lithiasic cholecystitis.

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“…Biliary sludge was diagnosed by low-amplitude echoes within the lumen of gallbladder with no post-acustic shadows and gallstone was diagnosed by mobile hyperechogenic material with post-acustic shadows. Biliary sludge was detected in one patient, and gallstones were detected in three sludge and/or lithiasis, named as pseudolithiasis, have been reported in patients treated with ceftriaxone (Lopez et al 1991). Pseudolithiasis due to ceftriaxone can occur both in children and adults.…”

confidence: 99%

Pseudolithiasis due to Ceftriaxone Treatment for Meningitis in Children: Report of 8 Cases

Araz¹,

Okan

Demırcı

et al. 2007

Tohoku J. Exp. Med.

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Ceftriaxone-induced Cholelithiasis

Cited by 61 publications

References 10 publications

Acute necrotizing cholecystitis: a rare complication of ceftriaxone-associated pseudolithiasis

Acute necrotizing cholecystitis: a rare complication of ceftriaxone-associated pseudolithiasis

Cholecystectomy during ceftriaxone therapy. A translational study with a new rabbit model

Pseudolithiasis due to Ceftriaxone Treatment for Meningitis in Children: Report of 8 Cases

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