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      Gallbladder pseudolithiasis caused by ceftriaxone in young adult

      case-report

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          Abstract

          Ceftriaxone is a commonly used antibiotic due to some of its advantages. Reversible gallbladder (GB) sludge or stone has been reported after ceftriaxone therapy. Most of these patients have no symptom, but the GB sludge or stone can sometimes cause cholecystitis. We experienced two patients who had newly developed GB stones after ceftriaxone therapy for diverticulitis and pneumonia, and this resolved spontaneously 1 month after discontinuation of the drug. Awareness of this complication could help to prevent unnecessary cholecystectomy.

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          Ceftriaxone. A review of its antibacterial activity, pharmacological properties and therapeutic use.

          Ceftriaxone is a new 'third generation' semisynthetic cephalosporin with a long half-life which has resulted in a recommended once daily administration schedule. It is administered intravenously or intramuscularly and has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria. The activity of ceftriaxone is generally greater than that of the 'first' and 'second generation' cephalosporins against Gram-negative bacteria, but less than that of the earlier generations of cephalosporins against many Gram-positive bacteria. Although ceftriaxone has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy in pseudomonal infections. Ceftriaxone has been effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae. Ceftriaxone was effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms. In most of these types of infections once-daily administration appears efficacious. Results were also encouraging in a few patients with ear, nose and throat, intra-abdominal, obstetric and gynaecological infections, and adult meningitis, but conclusions are not yet possible as to the efficacy of the drug in these indications due to limited experience. A single intramuscular dose of ceftriaxone has been compared with standard therapy for gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae and shown to be highly effective. In a few small trials the comparative efficacy of ceftriaxone and other antibacterials has been assessed in other types of infections and in perioperative prophylaxis in patients undergoing surgery. Few significant differences in response rates were found between therapeutic groups in these comparative studies, but larger well-designed studies are needed to more clearly assess the comparative efficacy of ceftriaxone and other antimicrobials, especially the aminoglycosides and other 'third generation' cephalosporins, and to confirm the apparent lack of serious side effects with ceftriaxone. If more widespread use confirms the safety and efficacy of ceftriaxone, it will offer an important alternative, particularly for the treatment of serious infections due to multidrug-resistant Gram-negative bacteria and in situations where the long half-life of the drug could result in worthwhile convenience and cost benefits.
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            A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

            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.

              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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                Author and article information

                Journal
                J Korean Surg Soc
                JKSS
                Journal of the Korean Surgical Society
                The Korean Surgical Society
                2233-7903
                2093-0488
                December 2011
                25 November 2011
                : 81
                : 6
                : 423-426
                Affiliations
                [1 ]Department of Surgery, The Armed Forces Gangneung Hospital, Gangneung, Korea.
                [2 ]Department of Internal Medicine, The Armed Forces Gangneung Hospital, Gangneung, Korea.
                [3 ]Department of Radiology, The Armed Forces Capital Hospital, Seongnam, Korea.
                [4 ]Department of Internal Medicine, The Armed Forces Pusan Hospital, Busan, Korea.
                [5 ]Department of Surgery, Soonchunhyang University College of Medicine, Seoul, Korea.
                Author notes
                Correspondence to: Kyung Yul Hur. Department of Surgery, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, 657 Hannam-dong, Yongsan-gu, Seoul 140-743, Korea. Tel: +82-2-709-9499, Fax: +82-2-749-0449, hurusa@ 123456hanmail.net
                Article
                10.4174/jkss.2011.81.6.423
                3243861
                22200045
                bfa27814-dc1a-4c3c-958a-1f8a7ac1bec2
                Copyright © 2011, the Korean Surgical Society

                Journal of the Korean Surgical Society is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 December 2010
                : 07 February 2011
                : 24 February 2011
                Categories
                Case Report

                Surgery
                cholecystolithiasis,gallstones,ceftriaxone
                Surgery
                cholecystolithiasis, gallstones, ceftriaxone

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