Safety of ceftriaxone in paediatrics: a systematic review

ObjectiveTo determine the safety of ceftriaxone in paediatric patients and systematically evaluate the categories and incidences of adverse drug reactions (ADRs) of ceftriaxone in paediatric patients.MethodsWe performed a systematic search in Medline, PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, International Pharmaceutical Abstracts and bibliographies of relevant articles up to December 2018 for all types of studies that assessed the safety of ceftriaxone in paediatric patients aged ≤18 years.Results112 studies met the inclusion criteria involving 5717 paediatric patients who received ceftriaxone and reported 1136 ADRs. The most frequent ADRs reported in prospective studies were gastrointestinal (GI) disorders (37.4 %, 292/780), followed by hepatobiliary disorders (24.6%, 192/780). Serious ADRs leading to withdrawal or discontinuation of ceftriaxone were reported in 86 paediatric patients. Immune haemolytic anaemia (34.9%, 30/86) and biliary pseudolithiasis (26.7%, 23/86) were the two major causes. Haemolytic anaemia following intravenous ceftriaxone led to death in 11 children whose primary disease was sickle cell disease. Almost all biliary pseudolithiasis are reversible. However, the incidence was high affecting one in five paediatric patients (20.7%).ConclusionsGI ADRs are the most common toxicity of ceftriaxone in paediatric patients. Immune haemolytic anaemia and biliary pseudolithiasis are the most serious ADRs and the major reasons for discontinuation of ceftriaxone. Immune haemolytic anaemia is more likely in children with sickle cell disease and may cause death. Ceftriaxone should be used with caution in children with sickle cell disease.Trial registration numberCRD42017055428

Symptomatic Biliary Pseudolithiasis in Adult Patients Treated with Parenteral Ceftriaxone: A Prospective Study

Introduction: Ceftriaxone is a frequently used antibiotic in inpatients treated for a number of bacterial infections. Biliary calculi formation called pseudolithiasis is a well-known asymptomatic and reversible complication of this drug. However, a percentage of patients do present with new onset of abdominal symptoms which can be attributable to presence of pseudoliths. Aim: To evaluate incidence of pseudolithiasis in inpatients treated with parenteral Ceftriaxone, to assess resolution of pseudoliths and development of abdominal symptoms attributable to pseudolithiasis on long term follow-up over one year. Materials and Methods: A prospective observational cohort study including all patients admitted at our centre and started on Ceftriaxone. These patients were subjected to sonographic examination on day 1 and day 7 of treatment. Patients who developed pseudolithiasis were prospectively followed-up at one month, three months, six months and one year to assess for resolution or whenever they presented with symptoms. Incidence of pseudolithiasis and complications in patients who developed pseudolithiasis was calculated using standard formulae. Descriptive statistics in terms of numbers and percentages were used. Results: A total of 1490 patients were included in the study from August 2016 till July 2017 and followed for a period of one year (June 2018). The incidence of pseudolithiasis in inpatients treated with parenteral ceftriaxone was 8.7% (131 patients) as observed on Sonographic examination performed on day 7 of therapy. Ten (7.6%) patients had pseudoliths at one month and 1 (0.76%) patient out of these had persistent pseudoliths at all subsequent reviews till one year after diagnosis of the condition. Eleven (8.3%) patients who developed pseudolithiasis during therapy with Ceftriaxone had presented with upper abdominal symptoms suggestive of biliary colic before resolution of pseudolithiasis. Conclusion: Biliary pseudolithiasis is a common side effect of ceftriaxone therapy, occurring in approximately 10% of patients. Biliary colic, cholecystitis and pancreatitis may also result due to these pseudoliths complicating the course of primary illness. Further consultations and interventions like cholecystectomy can be reserved not only to symptomatic individuals but also for those with persistent pseudoliths.