Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects

Area of Science:

• Pharmacology
• Critical Care Medicine
• Infectious Diseases

Background:

• Oxacillin and cloxacillin are primary treatments for severe methicillin-susceptible Staphylococcus aureus infections in ICUs.
• Current international guidelines do not recommend dosage adjustments for renal impairment.
• This study investigates overdose risks and side effects associated with these antibiotics in ICUs.

Purpose of the Study:

• To assess risk factors for oxacillin and cloxacillin overdosing in ICU patients.
• To identify and document side effects related to antibiotic overdosing.
• To evaluate the impact of renal function on antibiotic concentrations.

Main Methods:

• Therapeutic drug monitoring data for oxa- or cloxacillin from 2008-2014 were analyzed.
• Target trough concentration was defined as 20-50 mg/L.
• Logistic regression was used to identify factors associated with measured trough concentrations.

Main Results:

• A median trough plasma concentration of 134.3 mg/L was observed, significantly exceeding the target range.
• 83.9% of patients were overdosed, with only 16.1% achieving therapeutic levels.
• Neurological side effects, including coma and delirium, were reported in 17.7% of patients.
• Creatinine clearance <10 mL/min, with or without hemodialysis, was a significant risk factor for overdosing.

Conclusions:

• Standard dosing of oxacillin and cloxacillin (e.g., 12 g/day for cloxacillin) frequently leads to overdosing in ICU patients, particularly those with severe renal impairment.
• Observed neurological side effects highlight the need for dose monitoring and reduction, especially in patients undergoing renal replacement therapy.
• Accurate therapeutic drug monitoring and dose adjustment are crucial for optimizing treatment and minimizing adverse events in critically ill patients.