14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biliary pseudolithiasis secondary to ceftriaxone therapy

      letter
      ,
      Indian Journal of Pharmacology
      Medknow Publications

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sir, Ceftriaxone is a third-generation cephalosporin widely used for the treatment of a variety of bacterial infections in children.[1] It has a broad-spectrum antibacterial activity with a long plasma half-life that permits reduced dosing schedules as compared to other cephalosporins and penicillins.[2] These factors have lead to its increased use in public hospitals in developing countries. As this antibiotic becomes more commonly prescribed, practitioners should be aware of the potential adverse-effects of the drug, especially if the adverse-event can lead to medically inappropriate interventions. We herein report nine cases of biliary pseudolithiasis secondary to ceftriaxone therapy seen at our institution. There were nine children admitted between January to October 2009 who developed biliary pseudolithiasis after starting ceftriaxone therapy. The clinical and demographic characteristics of the patients are shown in Table 1. None of the patients had hemolytic anemia, renal or liver failure, cystic fibrosis or malignancy or had received total parenteral nutrition. None of them were taking other drugs known to be associated with biliary sludge and/or lithiasis. Complete blood count, reticulocyte count, serum calcium, liver and renal function tests were normal in these children. Their family and past history was unremarkable. All patients had received intravenous ceftriaxone (100 mg/kg/day) in two divided doses. Six patients developed abdominal pain within 1 week of starting ceftriaxone therapy and three patients developed abdominal pain after completion of their therapy, i.e. after 10 days. The abdominal pain was colicky, in the right hypochondriac region and without any aggravating or relieving factors. Ultrasonography of the abdomen was performed in all these symptomatic patients [Table 2]. Patients who developed biliary pseudolithiasis before completion of treatment were shifted to alternative therapy. All the patients responded within 1 week of stopping ceftriaxone therapy, with the ultrasonography showing no evidence of pseudolithiasis. Rechallenge with ceftriaxone was not carried out in our patients due to ethical constraints. This can be labelled as a type A class of adverse-effect. It can be considered as probable/likely adverse drug reaction as per causality assessment of suspected adverse drug reaction.[3] Table 1 Clinical and demographic characteristics of patients Patient Age (years) Sex Weight (kg) Diagnosis on admission A 7.5 M 20 Typhoid fever B 7.8 M 21 Typhoid fever C 8.2 M 20 Meningitis D 9.4 M 22.1 Typhoid fever E 10 M 24.2 Urinary tract infection F 10.6 F 21.2 Meningitis G 11 F 27.8 Meningitis H 12 F 25.6 Urinary tract infection I 12 F 24.3 Meningitis Table 2 Duration of ceftriaxone therapy and ultrasonographic findings of the patients Patient Duration of ceftriaxone therapy Abdominal pain FirstUSG Follow-up USG after 7 days A 6 On 6th day of admission 1.6 * 0.8 cm gall stone Normal B 6 On 6th day of admission 1.2 * 1 cm gall stone Normal C 10 On 12th day of admission 1.8 * 1.6 cm gall stone Normal D 6 On 6th day of admission 1.1 * 1.5 cm gall stone Normal E 5 On 5th day of admission 1 * 1.9 cm gall stone Normal F 10 On 13th day of admission 1.2 * 1.6 cm gall stone Normal G 10 On 11th day of admission 1.3 * 0.4 cm gall stone Normal H 5 On 5th day of admission 1.3 * 1.3 cm gall stone Normal I 6 On 6th day of admission 1.3 * 1.4 cm gall stone Normal The first sonographic demonstration of precipitates forming in the gallbladder during ceftriaxone therapy was reported by Schaad et al. in 1986.[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.[6] When the solubility of the drug exceeds, it leads to the formation of calcium–ceftriaxone salt precipitates that mimic gallstone on ultrasonography. With discontinuation of the drug, these “stones” resolve spontaneously, a phenomenon termed “reversible ceftriaxone biliary pseudolithiasis.”[7] The incidence of pseudolithiasis in children treated with ceftriaxone is up to 25%, but only a minority of these patients become symptomatic.[2] Papadopoulou et al. 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).[2 6] Conservative management of ceftriaxone-associated “pseudolithiasis” is suggested in managing this clinical entity with serial ultrasounds until complete resolution of “stone” formation.[2] In conclusion, patients receiving a high dose of ceftriaxone and developing colicky abdominal pain should be considered for ultrasound and a change in antibiotic if appropriate. Recognition of this complication will prevent unnecessary surgical interventions.

          Related collections

          Most cited references7

          • Record: found
          • Abstract: found
          • Article: not found

          Reversible ceftriaxone-associated biliary pseudolithiasis in children.

          Serial abdominal ultrasonography was performed in 37 children being treated with ceftriaxone for serious infections. Biliary concrements developed in 16 patients, causing symptoms in 3, one of whom also had urolithiasis with renal colic and obstructive ureteropyelectasia. After cessation of ceftriaxone treatment, ultrasound abnormalities and symptoms gradually disappeared, with complete sonographic resolution after 2 to 63 days.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Incidence of ceftriaxone-associated gallbladder pseudolithiasis.

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis.

              Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. In addition to biliary sludge formation occasional reports of ceftriaxone-induced nephrolithiasis have been published. In general, these adverse effects will develop after seven to ten days of treatment. We report on a seven-year-old boy with ceftriaxone-associated biliary pseudolithiasis and nephrolithiasis four days after initiation of treatment. Patients receiving a high dose of ceftriaxone and developing colicky abdominal pain should be considered for ultrasound and a change in antibiotic therapy if appropriate.
                Bookmark

                Author and article information

                Journal
                Indian J Pharmacol
                IJPharm
                Indian Journal of Pharmacology
                Medknow Publications (India )
                0253-7613
                1998-3751
                June 2010
                : 42
                : 3
                : 193-194
                Affiliations
                Department of Pediatrics, Lokmanya Tilak Municipal General Hospital, Mumbai, India
                Author notes
                Correspondence to: Syed Ahmed Zaki E-mail: drzakisyed@ 123456gmail.com
                Article
                IJPharm-42-193
                10.4103/0253-7613.66847
                2937325
                20871775
                a3e00a84-d1de-44b7-8c68-58161a61b4b0
                © Indian Journal of Pharmacology

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Letters to Editor

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

                Comments

                Comment on this article