Haematological and hepatic adverse effects of ceftriaxone in ambulatory care: a dual-centre retrospective observational analysis of standard vs high dose

Background: European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients.

Method: Adult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher's exact test used to identify statistical significance.

Results: Incidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87-2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36-10.92), p 0.655).

Conclusions: Increased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable-monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.