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      Ceftriaxone pseudolithiasis detected by computed tomography and followed up until resolution

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          Abstract

          Introduction: Ceftriaxone is a third-generation cephalosporin antibiotic that has been widely used to treat various infectious diseases. We report a case of ceftriaxone pseudolithiasis that was detected by computed tomography (CT) and followed up until it was resolved.

          Case: A 76-year-old woman with diabetes mellitus and renal impairment, but no history of gallstones, was diagnosed with septic shock due to renal and lung abscesses and treated with ceftriaxone. On day 22 after admission, abdominal CT revealed a gallstone, which increased in size up to day 50. Ceftriaxone was stopped on day 50, and the gallstone resolved completely after 10 weeks.

          Conclusion: Ceftriaxone pseudolithiasis should be cautiously considered, specifically in a patient with renal impairment and a prolonged treatment period.

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          Most cited references14

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          A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

          J Wedgwood, R Auckenthaler, J J Cheseaux … (1990)
          To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.
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            Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility.

            Sophie E. Moore, Ashley B Keith, M Shiffman (1990)
            Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone-associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone-induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying.
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              Sonographic assessment of ceftriaxone-associated biliary pseudolithiasis in children.

              N Guler, N Salman, E Tonguç … (2000)
              Ceftriaxone is a widely used third-generation cephalosporin. In this prospective study, we used sonography to investigate the incidence and outcome of biliary complications in children receiving ceftriaxone therapy. Ceftriaxone was administered intravenously at a dosage of 100 mg/kg/day for 1-3 weeks to 118 children hospitalized for severe infection. Serial gallbladder sonograms were obtained on days 1, 5-7, and 10-14 of therapy and the day after therapy ended if it had lasted more than 2 weeks. When sonographic abnormalities were found, additional sonograms were obtained every 3 days until the abnormalities had completely resolved. Twenty patients (17%), all asymptomatic, demonstrated sonographic abnormalities: 8 had gallbladder sludge, defined as echogenic material without associated acoustic shadowing, and 12 had pseudolithiasis, defined as echogenic material with acoustic shadowing. These abnormalities spontaneously resolved within 2 weeks of stopping the ceftriaxone (mean time to disappearance, 8.2 +/- 3.4 days). No significant differences were found between patients with normal versus abnormal sonographic findings in sex, age, duration of treatment, or other risk factors for drug precipitation. Ceftriaxone-associated biliary pseudolithiasis is usually asymptomatic and was rapidly reversible after cessation of therapy in this group of Turkish children. Copyright 2000 John Wiley & Sons, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Rural Med
                Journal ID (publisher-id): JRM
                Title: Journal of Rural Medicine : JRM
                Publisher: The Japanese Association of Rural Medicine
                ISSN (Print): 1880-487X
                ISSN (Electronic): 1880-4888
                Publication date (Electronic): 1 October 2020
                Publication date (Print): October 2020
                Volume: 15
                Issue: 4
                Pages: 230-233
                Affiliations
                [1 ]Department of General Medicine, Mito Kyodo General Hospital, Japan
                [2 ]Department of Gastroenterology, Mito Kyodo General Hospital, Japan
                Article
                Publisher ID: 2020-020
                DOI: 10.2185/jrm.2020-020
                PMC ID: 7530589
                SO-VID: 4f74b9ba-2d2c-4348-9108-7855642dc5c8
                Copyright © ©2020 The Japanese Association of Rural Medicine
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

                History
                Date received : 27 April 2020
                Date accepted : 11 June 2020
                Categories
                Subject: Case Report

                Keywords: ceftriaxone,pseudolithiasis,gallstone
                Data availability:
                Keywords: ceftriaxone, pseudolithiasis, gallstone

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