Haematological and hepatic adverse effects of ceftriaxone in ambulatory care: a dual-centre retrospective observational analysis of standard vs high dose
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Author(s)
Type
Journal Article
Abstract
Background
European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4g/day) rather than standard dose (2g/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 2g group vs 6/39 (15.4%) in the 4g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2g and 4g groups respectively. Thrombocytopenia was observed in 0/47 in the 2g group compared with 3/39 (7.7%) in the 4g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2g and 4g 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 2g and 3/39 (7.7%) for 4g (OR 1.86 (95% CI 0.36 – 10.92), p 0.655).
Conclusions
Increased adverse effects with 4g (over 2g) 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.
European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4g/day) rather than standard dose (2g/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 2g group vs 6/39 (15.4%) in the 4g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2g and 4g groups respectively. Thrombocytopenia was observed in 0/47 in the 2g group compared with 3/39 (7.7%) in the 4g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2g and 4g 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 2g and 3/39 (7.7%) for 4g (OR 1.86 (95% CI 0.36 – 10.92), p 0.655).
Conclusions
Increased adverse effects with 4g (over 2g) 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.
Date Issued
2022-12-24
Date Acceptance
2022-12-06
Citation
BMC Infectious Diseases, 2022, 22
ISSN
1471-2334
Publisher
BioMed Central
Journal / Book Title
BMC Infectious Diseases
Volume
22
Copyright Statement
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Publication Status
Published
Article Number
ARTN 959