Ceftriaxone induced gallbladder lithiasis in children

Transcription

1 Ceftriaxone induced gallbladder lithiasis in children Poster No.: C-1329 Congress: ECR 2014 Type: Authors: Keywords: DOI: Educational Exhibit L. N. Santos 1, M. A. Olivier Barbosa 1, A. Lupi Benavides 2 ; 1 Mexico city, DF/MX, 2 Mexico/MX Calcifications / Calculi, Treatment effects, Ultrasound, Pediatric, Gastrointestinal tract, Biliary Tract / Gallbladder, Drugs / Reactions /ecr2014/C-1329 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 8

2 Learning objectives Describe the pathophysiology of gallstone disease as a side effect from the use of ceftriaxone. Characterize gallstones by ultrasound in children under antibiotic ceftriaxone treatment. Background Gallstones in children occurs secondary to predisposing factors such as hemolytic anemia, hepatobiliary disease, total parenteral nutrition, sepsis, intestinal resection, or as a side effect of drugs such as ceftriaxone, octreotide or furosemide. Ceftriaxone is one of the most commonly used third generation parenteral cephalosporins because it has wide spectrum of anti-microbial activity, a long plasma half-life that allows once-daily administration and it can even penetrate the blood brain barrier (Table 1). Ceftriaxone could have potential complications and these are biliary sludge or biliary lithiasis, and even urinary tract precipitation, because up to 40% of the drug is excreted unchanged into the bile and subsequent precipitation as insoluble calcium salt., Numerous studies have tried to clarify the underlying pathogenesis of ceftriaxone induced pseudolithiasis. Beginning with the chemical composition of fine lithogenic precipitations, it should be stated that they are mainly consisted of cholesterol monohydrate and calcium bilirubinate. It is also known that cholesterol precipitates when the cholesterol-solubilizing power of bile acid mixed micelles and phospholipid vesicles is overwhelmed. In addition, bilirubin is excreted as a soluble diglucuronide and deconjugation, either by nonenzymatic hydrolysis or by P-glucuronidase, results in free bilirubin. When the solubility product of calcium and unconjugated bilirubin is exceeded, calcium bilirubinate precipitates. These complication may be reversible upon discontinuation of ceftriaxone; and usually there are no complications unless there are comorbidities such as immunodeficiencies or hemolytic anemia, although there are other side effects (Table 2). Usually it is an incidental ultrasound finding in children who are studied by abdominal pain from other cause. Ceftriaxone associated pseudolithiasis is fairly frequent in children, but rarely taken into account. It occurs in 15% to 57% of children as early as the second day of tratment, and in most cases is asymptomatic and disappears in less tha 2 months. Various terms, such as "pseudolithiasis" or "reversible lithiasis", have been used. Not clear the pathogenesis of this disease, although in the cases reported in the literature, is necessarily an infectious process requiring administration of ceftriaxone. It has been found in genomic data matched patients with this condition, including the A(TA)7TAA Page 2 of 8

3 polymorphism of the UGT1A1 gene. UGT1A1 encodes UDP-glucuronosyltransferase (UDPG), an enzyme engaged in the glucuronidation pathway that transforms small lipophilic molecules, (i.e., steroids, bilirubin, hormones, and drugs) into water-soluble, excretable metabolites. A broad-spectrum with a very long half-life and high penetrability to meninges, eyes and inner ears. For the treatment of the infections caused by S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph The bactericidal activity of Ceftriaxone results from the inhibition of cell wall synthesis and is mediated through Ceftriaxone binding to penicillin binding proteins (PBPs). Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. Table 1. Pharmacological properties of ceftriaxone Eosinophilia Thrombocytosis Leukopenia Hypersensitivity Reactions Gastrointestinal Effects Table 2. Adverse effects associated with the use of ceftriaxone. PRESENTATION OF THE DISEASE All the patients usually receive (100 mg / kg / day), developed gallbladder pseudolithiasis with typical sonographic appearance: intense, mobile, echogenic material with acoustic shadow (Figure 1, 2). Laboratory investigation revealed normal blood cell count without overt hemolysis, liver and renal function tests within normal limits, as well as serum lipids and electrolytes. Patients may have abdominal pain from other causes and to perform ultrasound assessment are evident gallstones. When it is diagnosed pseudolitiasis ceftriaxone should be discontinued and monthly ultrasound monitoring is recommended until the resolution (Figure 3). Page 3 of 8

4 Images for this section: Fig. 1: Female patient 1 year of age with severe abdominal pain and intolerance to oral history ceftriaxone treatment. Gallstones than 1 cm in diameter, located in the neck is shown. Page 4 of 8

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6 Fig. 2: Using color Doppler mode demonstrates hyperemia wall Fig. 3: Fifteen days after the drug suspended, gallbladder without echoes observed inside and thin wall. Page 6 of 8

7 Findings and procedure details Ultrasound with transducer MHz is the method for the study of abdominal pain in children since it does not emit radiation and is accessible. When the infant is placed supine cooperative situation and is reviewed with convex or linear multifrequency transducer, if it is required it can hold in their arms to facilitate exploration. Gallbladder is scanned, it shows its size, wall thickness, if thickening, color Doppler mode is applied to determine probable hyperemia, the most important is to mobilize the patient for the vesicular content, when the stone was located, characterized. It is also important to assess the caliber of the common bile duct. After stopping the medication is recommended to repeat the study to determine if the stone has disappeared. Conclusion Cholelithiasis is a rare side effect of ceftriaxone and complete resolution to discontinue the drug, so it does not require surgical treatment. In the pathogenesis of this disease has been found in genomic data matched patients with this condition, including the A(TA) 7 TAA polymorphism of the UGT1A1 gene. UGT1A1 encodes UDPglucuronosyltransferase (UDPG), an enzyme engaged in the glucuronidation pathway that transforms small lipophilic molecules, (i.e., steroids, bilirubin, hormones, and drugs) into water-soluble, excretable metabolites. Personal information References 1. Meng D. Sonographic assessment of ceftriaxone associated biliary pseudolithiasis in Chinese children. J Int Med Res ; 38(6): Soysal A. Biliary precipitation during ceftriaxone therapy: frequency and risk factors. - Turk J Pediatr 2007; 49(4): Dinleyici EC. Ceftriaxone associated cholelithiasis: 30 min drip infusion versus bolus injection. Pediatr Int ; 52(6): Jeffrey S. Ceftriaxone associated nephrolithiasis and biliary pseudolithiasis in a child. Pediatric Radiology. 2003: 33 (9) Betul Biner MD. Ceftriaxone associated biliary pseudolithiasis in children. Journal of Clinical Ultrasound. Vol 34, Issue Page 7 of 8

8 6. A. Ozturk, Ultrasonographic Findings in Ceftriaxone: Associated Biliary Sludge and Pseudolithiasis in Children. Harran University Of Medicine. 2005; 46 (1): Page 8 of 8