Antibiotic Administration Guidelines

Introduction to Antibiotic Administration

Antibiotics should be administered within 1 hour of recognizing septic shock, as recommended by the European Society of Intensive Care Medicine 1
Administering a full dose of broad-spectrum antibiotics, including a loading dose, is recommended in the first 24 hours of septic shock, regardless of renal function, to rapidly achieve therapeutic concentrations and optimize antimicrobial efficacy, as stated by the Critical Care Medicine and Intensive Care Medicine guidelines 2, 3

For patients with normal renal function, doripenem should be administered at 500 mg every 8 hours as a 1-hour infusion, while patients with impaired renal function require dose adjustments based on creatinine clearance 4, 5
Doripenem 500 mg every 8 hours is recommended for critically ill patients with intra-abdominal infections, particularly those at risk for infection with ESBL-producing Enterobacteriaceae 4, 5
Loading doses of antimicrobials should be administered at full dose to rapidly achieve therapeutic concentrations, regardless of renal function, as recommended by the Society of Critical Care Medicine 2
A loading dose of 25-30 mg/kg based on actual body weight is recommended for vancomycin, as suggested by the European Society of Intensive Care Medicine 3

Consider therapeutic drug monitoring in critically ill patients, especially those with fluctuating renal function 6
Target plasma trough concentration for intermittent administration and steady-state concentration for continuous administration 6
Perform monitoring 24-48 hours after treatment initiation, after dosage changes, or with significant changes in clinical condition 6
Therapeutic drug monitoring is strongly recommended for critically ill patients with sepsis and AKI, particularly for aminoglycosides, vancomycin, and β-lactams, as recommended by the European Society of Intensive Care Medicine 1
Measure peak and trough levels for aminoglycosides, monitor trough levels or steady-state concentration for vancomycin, and consider monitoring residual concentrations for β-lactams, as suggested by the European Society of Intensive Care Medicine 1

Residual renal function in patients on renal replacement therapy can significantly impact clearance and should be considered when determining dosage 6
For antibiotics with low volume of distribution, such as vancomycin, teicoplanin, and colistin, higher loading doses are particularly important, according to the European Society of Intensive Care Medicine 3
Septic patients with AKI have significant pathophysiological changes affecting drug disposition, including increased cardiac output, increased extracellular volume, variable kidney and hepatic perfusion, and altered drug binding due to reduced serum albumin, as described by the Society of Critical Care Medicine 3
Augmented renal clearance may occur in early sepsis despite AKI, as reported by the Society of Critical Care Medicine 2
Patients with sepsis present with physiological alterations that significantly affect antibiotic pharmacokinetics, including increased volume of distribution, altered renal and hepatic perfusion, decreased plasma proteins, and increased renal clearance, as reported by the Critical Care Medicine society 2

For β-lactams, target 100% time above MIC for optimal response in severe infections, as recommended by the Society of Critical Care Medicine 2
Consider extended or continuous infusions after initial bolus dose for β-lactams, as suggested by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine 2, 3
For aminoglycosides, optimize peak concentrations (5-7 mg/kg daily gentamicin equivalent) and consider once-daily dosing, as recommended by the European Society of Intensive Care Medicine 3
Imipenem is highly effective against a wide range of common pathogens in septic shock, including gram-negative aerobic bacteria, gram-positive bacteria, anaerobes, and Enterobacteriaceae producing ESBL, as stated by the World Journal of Emergency Surgery guideline 4

After the first 24 hours, the dose should be adjusted based on renal and hepatic function, culture and antibiogram results, clinical response, and serum level monitoring when available, as recommended by the Intensive Care Medicine and Critical Care Medicine societies 3, 2
Patients with renal insufficiency on hemodialysis are at risk of adverse effects, including seizures, nausea, and vomiting, as well as accumulation of cilastatin, a component of the imipenem formulation, and should be monitored closely for signs of toxicity, particularly neurotoxicity, as recommended by the Critical Care Medicine guidelines 4, 2
The antibiotic regimen should be reevaluated daily, considering extended infusion for beta-lactams, and using therapeutic monitoring when available, with a strength of evidence based on clinical guidelines, as recommended by the Intensive Care Medicine society 3, 2