Incidence of ceftriaxone-associated gallbladder pseudolithiasis

Abstract

We prospectively evaluated the incidence of gallbladder pseudolithiasis in children treated with high doses of ceftriaxone for a variety of serious infections. We also monitored the time interval needed for this phenomenon to develop and resolve completely after initiation and cessation of treatment, respectively. Included in this study are 44 children treated with ceftriaxone 100 mg/kg/d divided into 2 equal intravenous doses and followed by serial abdominal sonography. Eleven children developed pseudolithiasis of gallbladder 2-9 d after initiation of ceftriaxone therapy. Six children (54.5%) developed this complication within the first 3 d. Lithiasis completely resolved 8-23 d after the end of treatment. In conclusion, pseudolithiasis of the gallbladder developed in 25% of sick children and completely resolved in all patients. Early development of this complication was not exceptional. It occurred in more than half of these children.

A case of ceftriaxone-associated biliary pseudolithiasis in an elderly patient with renal dysfunction

“…Onset of pseudobiliary stones varies from 2 to 22 days after starting treatment with ceftriaxone [2], [4], [10], [11], [12]. Kimura reported that stones appeared on day 30 after the end of 12 days of ceftriaxone administration [5].…”

“…Kimura reported that stones appeared on day 30 after the end of 12 days of ceftriaxone administration [5]. Generally, spontaneous exclusion (or disappearance) of the stones occurs relatively quickly after stopping ceftriaxone administration, but the period varies from 2 days to 5 months after the discontinuation of ceftriaxone administration [3], [4], [5], [8], [10], [12], [13]. In an in vitro study, at doses of ceftriaxone greater than or equal to 2 g, precipitation of ceftriaxone could occur, and the development of ceftriaxone-induced biliary sludge could be because of poor solubility that occurs in patients receiving a high-dose treatment (greater than or equal to 2 g) [6].…”

Treatment Options for Gram-Positive and Gram-Negative Bacteria: Focus on Ceftriaxone

“…In adults, biliary pseudolithiasis may occur 4-22 days after the start of high-dose (more than 2 g/day) ceftriaxone therapy, at a cumulative dose of approximately 28 g, and may resolve 3-63 days after the discontinuation of therapy. [148][149][150] Previous studies have shown that biliary pseudolithiasis, which was diagnosed by abdominal ultrasonography, was observed in 12 to 43% of adolescents and children and 21% and 25% of adults treated with intravenous ceftriaxone. 4 Three of 29 patients with streptococcal endocarditis treatment with intravenous ceftriaxone developed biliary pseudolithiasis.…”

Biliary pseudolithiasis secondary to ceftriaxone therapy

“…[4] In subsequent reports, biliary sludge or biliary pseudolithiasis has frequently been reported with this antibiotic. [5] Ceftriaxone is mainly excreted in the urine and a significant proportion (40%) is also secreted in the bile and then eliminated via the gastrointestinal tract. [2] It is secreted unmetabolized into bile in concentrations 20–150-times that of serum concentrations and is further concentrated in the gall bladder as a calcium salt.…”

“…described 25% of children on high-dose ceftriaxone therapy (>100 mg/kg per day) developing pseudolithiasis, with only 4% having right-upper quadrant pain in association with these ultrasonographic changes. [5] Precipitates form after 4–22 days (mean, 9 days) of treatment and resolve within 2–63 days (mean, 15 days) after cessation of therapy. [8] Risk factors for biliary pseudolithiasis formation include age greater than 24 months, gram-negative sepsis, high doses of ceftriaxone (≥2 g/day), increased calcium secretion into bile (e.g., hypercalcemia), post surgery, decreased bile flow (e.g., fasting or total parenteral nutrition) and increased ceftriaxone excretion in bile (e.g., renal failure or long-term treatment with ceftriaxone).…”