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Ceftriaxone‐associated cholelithiasis: 30 min drip infusion versus bolus injection

Ceftriaxone, a third-generation cephalosporin, is still the preferred antimicrobial for treating infection during childhood in both ambulatory and hospital settings. Previously we published a prospective, open-label study on ceftriaxone in 2004. We prospectively evaluated 38 children aged between 1 month and 17 years who were evaluated on ultrasound at the initiation of ceftriaxone therapy and on the 10th day of therapy, consecutively. Abnormal gallbladder sonograms were demonstrated in 36.8% of patients on the 10th day of therapy and cholelithiasis was detected in 28.9% of patients and biliary sludge was detected in 7.9%. Two children still had cholelithiasis on the 30th day after therapy, and cholelithiasis disappeared at 90th day. Schaad et al. reported that i.v. drip infusion of ceftriaxone is better than bolus injection. In the present study we conducted a prospective, open label investigation of sonographic evaluation of 30 min drip infusion of ceftriaxone therapy in children, with the intention of comparing the results with those of the previous study. Thirty-two consecutive hospitalized children (18 boys, 14 girls, aged 6 months–16 years) in the Pediatric Unit in the Faculty of Medicine, Eskisehir Osmangazi University, Turkey, were included. The study was approved by the institutional ethics comities and parents gave written consent. They received ceftriaxone therapy for bacterial meningitis (n = 14), urinary tract infections (n = 11) and community-acquired pneumonia (n = 7). All the patients received 100 mg/kg ceftriaxone daily and two equal doses of drip infusion during 30 min. Children who had a history of total parenteral nutrition or drugs that caused stone formation were excluded. Abdominal sonography was performed before the first day of therapy and on the 10th day of therapy. If abnormal, scans were repeated every month until abnormalities disappeared. All ultrasound examinations were performed after 8 h of fasting, except during infancy when fasting was 4-6 h. Sonography was performed using a Toshiba 270 SSA (Toshiba, Japan) with 3.75 mHz convex-air transducer, on an empty stomach, in the morning. Statistical analysis was performed using SPSS for Windows 17.0 (SPSS, Chicago, IL, USA). At initiation of therapy all sonograms were normal. Abnormal gallbladder sonograms were demonstrated in 28.1% (n = 9) of patients on the 10th day of therapy. Cholelithiasis was detected in 9.3% (n = 3) of patients and biliary sludge was detected in 18.7% (n = 6). Cholelithiasis still persisted on ultrasound in one 7-year-old boy with bacterial meningitis (3.1%) and disappeared on the 60th day of therapy. When we compare the present study results with those of the previous study, demographic and clinical findings were similar between the study groups; the presence of abnormal gallbladder sonograms including biliary sludge and cholelithiasis were lower in the 30 min infusion group (28.1%) than the previous bolus injection group (36.8%), without statistical difference (P > 0.05). When we compared the incidence of cholelithiasis between the drip infusion group and bolus injection group, the incidence of cholelithiasis was lower in the drip infusion group (9.3%) than in the bolus injection group (28.9%; 3/32 children in drip infusion group vs 11/38 children in the bolus injection group; Fisher’s exact test, P = 0.07; two-sided test). Ceftriaxone-associated pseudocholelithiasis is a very well known, benign and recovering condition and clinical signs are usually absent. The present study was a prospective cohort study on the comparison of bolus versus drip infusion of ceftriaxone in children, and there are few previous reports evaluating the incidence between these two groups. Schaad et al. reported that cholelithiasis was confirmed in 55% of patients who received 3-5 min injections and in 29% who received 30 min injections. The present results on the occurrence of abnormal biliary sonograms with 30 min infusion of ceftriaxone are similar to those of the Schaad et al. study, while the present results also indicate that occurrence of cholelithiasis was low in the 30 min infusion group (9.3% vs 28.9%, P = 0.07), without statistical difference. According to the results, bolus drip infusion of ceftriaxone therapy is safer than bolus injection. The present sample size was small, so further randomized controlled trials are needed on pharmacodynamic profile, efficacy and other adverse events associated with infusion therapy of ceftriaxone in large cohorts.