Gallbladder and urinary tract precipitations associated with ceftriaxone therapy in children: a prospective study

Acun, Ceyda; Erdem, L. Oktay; Söğüt, Ayhan; Erdem, C. Zuhal; Tomaç, Nazan; Gündoğdu, Sadi; Cavuldak, S.

doi:10.1179/027249304225013349

Cited by 15 publications

(25 citation statements)

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“…While various researchers have drawn a connection between high doses (>100 mg/kg daily) during extended treatment periods with the development of urinary stones [1,5,12], this problem also occurs at normal dose levels [6,8]. In agreement with these findings, we failed to show a strong relationship between ceftriaxone dose and the uCa/ Cr.…”

Section: Discussioncontrasting

confidence: 61%

“…As an anion, ceftriaxone readily forms an insoluble salt with calcium in a 1:1 molar ratio that is capable of precipitation once the solubility of the salt is exceeded [6,[10][11][12]. These biochemical characteristics of ceftriaxone treatment frequently cause biliary sludge or pseudolithiasis, a well-known side effect in children [2][3][4][5]. This complication may develop after 2-16 days of treatment initiation [4-6, 13, 14] and is characterized by asymptomatic biliary changes; in most cases, it is reversible [3,13].…”

Section: Discussionmentioning

confidence: 98%

“…It has been well established that the administration of ceftriaxone administration is associated with biliary pseudolithiasis in children [2][3][4][5]. Although the development of urolithiasis or sludge in the urinary tract was believed to be rare [1,6], recent observations have revealed that the prevalence of both is higher than previously thought [5,7,8]. Despite several trials, the mechanism(s) underlying the formation of ceftriaxone-associated urolithiasis remain unclear [7,8].…”

Section: Introductionmentioning

confidence: 95%

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Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis

et al. 2011

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The administration of ceftriaxone is known to be associated with biliary pseudolithiasis, although the development of urolithiasis has only rarely been reported. We treated a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt, which prompted us to study whether ceftriaxone administration predisposes children to the formation of urinary precipitates. The case-control study reported here included 83 children with bacterial pneumonia aged from 3 months to 8.9 years. The children were divided into one group of 43 children who received ceftriaxone (group A) and a second group of 40 children who received amoxicillin (group B). Paired samples of serum and urine before and after treatment were obtained from the patients in each group. There were no significant differences in demographic characteristics and blood biochemistry between the groups. However, the mean urinary calcium to creatinine ratio (uCa/Cr; mg/mg) was significantly higher in group A patients than in group B patients after treatment (0.19 vs. 0.09, respectively; p < 0.001), and analysis of the paired urine samples revealed that the uCa/Cr significantly increased after treatment only in group A patients(p < 0.001). There was a weak but non-significant relationship between the dose of ceftriaxone and the uCa/Cr in group A (p = 0.10, r = 0.24). Our results are the first to demonstrate that ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. We therefore suggest that it is worthwhile monitoring the uCa/Cr levels in patients on ceftriaxone as they may be at greater risk for developing large stones and renal damage.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 95%

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Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis

et al. 2011

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“…Contrary to biliary pseudolithiasis caused by cephtriaxone treatment, the pathogenesis of urinary stones of the same origin has still remained far less satisfactorily explained [2][3][4][5][6][7]. Some investigations point to possible association with increased urinary calcium excretion, although majority of reports declare unclear results.…”

Section: Introductionmentioning

confidence: 99%

Urine saturation and promoter/inhibitor parameters and ratios in renal stone disease caused by ceftriaxone

et al. 2013

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AbstractDuring ceftriaxone treatment of subdural empyema caused by Streptococcus intermedius urinary and biliary stones were noticed. Increased levels of urinary calcium excretion were detected during ongoing treatment in comparison with 2 months check-up. There were no significant changes in the promoter/inhibitor urolithiasis parameters, oxalate, citrate, urate, cistine, glycosaminoglycans or their ratios. Urine saturation was calculated using EQUIL 2 computer programme (calcium oxalate, brushite) and it was normal. Probable trigger for the ceftriaxone/calcium hydroxy carbonate phosphate mixture of stones was a critical boost of solubility products caused by ceftriaxone treatment and phospnate urine content with a subsequent large-scale spontaneous precipitation of crystals.

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“…All stones were small (2 mm) and disappeared spontaneously in three cases. Arcun et al, in their series of 35 children treated with CTX, demonstrated gallbladder precipitation in five children; only one of these had associated urinary bladder sludge [3].Risk factors for CTX-induced urolithiasis are positive familiar history, high CTX dose, rapid infusion rate, dehydration and combination with nephrotoxic drugs [1,8,9,10,11]. Although biliary and urinary tract CTX precipitations are mainly asymptomatic and reversible, patients at risk should have routine ultrasound examination during CTX therapy.…”

mentioning

confidence: 97%

Nephrolithiasis in a child with acute pyelonephritis: Answer

Tasic

Sofijanova

Avramoski³

2005

Pediatr Nephrol

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AnswerCeftriaxone-induced nephrolithiasis and biliary pseudolithiasis. Infrared spectroscopy revealed that the stone was composed of calcium ceftriaxonate. CommentaryNephrolithiasis in children is principally caused by metabolic factors, obstruction and urinary tract infection. In our case there was no anatomical abnormality of the urinary tract. Urinary tract infection, which was caused by E. coli, had a very favorable clinical course. Appearance of echogenic material in the gallbladder and urinary tract is very suggestive of ceftriaxone (CTX)-induced precipitates. Clinical studies have demonstrated that CTX can induce reversible precipitations in gallbladder with posterior acoustic shadowing, which mimics cholelithiasis [1,2,3,4,5,6]. This complication is termed "biliary pseudolithiasis" or "reversible cholelithiasis". Gallbladder sludge is defined as echogenic material without associated acoustic shadowing. Most patients are asymptomatic, but in a few cases right upper quadrant pain, nausea, vomiting, and even cholecystitis may develop. Clinicians should be aware of these phenomena in order to save patients from unnecessary interventions.Risk factors for CTX-induced gallbladder precipitations are: high-dose CTX therapy (>2 g/day), increased calcium secretion into the bile (hypercalcaemia), decreased bile flow (such fasting or total parenteral nutrition), renal failure and gallbladder stasis after major surgical operations. Although high-dose, long-term CTX therapy is incriminated for this complication, Blais and Duperval reported a case where 48 h of therapy were sufficient for biliary pseudolithiasis to develop [7].There are only a few reports on ceftriaxone-induced nephrolithiasis [1,8,9,10,11]. Among the patients from the original series of Shaad et al, who first reported on CTX-induced biliary pesudolithiasis in 1988 [1], one child was found to have renal colic and obstruction caused by multiple stones. The clinical symptoms were transitory and impairment of renal function resolved after cessation of CTX therapy. Prince and Senac reported a case of both ceftriaxone-induced biliary pseudolithiasis and nephrolithiasis [8]. Their patient presented with acute renal failure due to bilateral ureteral obstruction with calculi, which necessitated placement of ureteral stents. De Moor et al reported a seven-year-old boy who developed biliary pseudolithiasis and nephrolithiasis four days after initiation of treatment with CTX [9]. Avci et al prospectively followed 51 children with various infections who were treated with CTX, and found that 4 (7.8%) developed nephrolithiasis [10]. All stones were small (2 mm) and disappeared spontaneously in three cases. Arcun et al, in their series of 35 children treated with CTX, demonstrated gallbladder precipitation in five children; only one of these had associated urinary bladder sludge [3].Risk factors for CTX-induced urolithiasis are positive familiar history, high CTX dose, rapid infusion rate, dehydration and combination with nephrotoxic drugs [1,8,9,10,11]. Although bilia...

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Gallbladder and urinary tract precipitations associated with ceftriaxone therapy in children: a prospective study

Cited by 15 publications

References 15 publications

Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis

Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis

Urine saturation and promoter/inhibitor parameters and ratios in renal stone disease caused by ceftriaxone

Nephrolithiasis in a child with acute pyelonephritis: Answer

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