Gentamicin dosing in critically ill patients

Abstract

Gentamicin is used worldwide in the treatment of serious infections in critically ill patients. The therapeutic efficacy of gentamicin is correlated to the peak serum concentration and the adverse effects to the trough concentrations. Information concerning the pharmacodynamics in critically ill patients is scarce, but pharmacokinetic data are available. A once-daily dosage regimen has replaced multiple dosing of gentamicin in most intensive care units. No studies evaluating the superiority of either of these dosage recommendations in critically ill patients have ever been conducted. Based on 8 meta-analyses performed addressing this issue on a wide range of patients and theoretical considerations, we consider a once-daily dosage regimen feasible in critically ill patients. In septic patients the volume of distribution is significantly increased compared to normal patients, implying that the initial dose should be increased in this patient population. Additionally a general trend towards using higher loading doses (5-7 mg/kg) has been observed in USA, and the appropriateness of this dosing strategy is based on a large descriptive American study. We recommend that the initial dosage of gentamicin in critically ill hyperdynamic septic patients should be 7 mg/kg. Optimal and appropriate monitoring of the treatment with gentamicin in the critically ill patient is still an issue for further investigation. The treatment period with gentamicin should be short (3-5 days), bearing the pharmacological properties of aminoglycosides (small volume of distribution and poor tissue penetration) in mind. In patients with reduced renal function the initial dose of gentamicin should also be increased and maintenance dose reduced preferentially by prolonging the dosing intervals. However, the use of aminoglycosides in a high dose regimen in oliguric or anuric patients or patients who present with a rapidly decreasing renal function needs further consideration.

Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis

“…1. This is contrary to what has been described with drugs such as aminoglycosides and vancomycin [4,[9][10][11][12]. Aminoglycosides and vancomycin distribute into extracellular fluids [13,14].…”

“…Aminoglycosides and vancomycin distribute into extracellular fluids [13,14]. The volume of distribution for these drugs may increase in the critically ill patient as a result of fluid shifts and, as a consequence, higher doses than those conventionally recommended may be needed to optimise plasma concentrations and to ensure clinical efficacy [4][5][6][9][10][11][12]. The volume of distribution of aminoglycosides and vancomycin therefore changes over the time-course of a severe infection [9,11].…”

Gentamicin Pharmacokinetics in Term Newborn Infants Receiving High-frequency Oscillatory Ventilation or Conventional Mechanical Ventilation: A Case-controlled Study

“…Based on their reported V d of 0.98±0.46 l/kg and K el of 0.081 þ 0.02/hour of patients in the HFOV group, the above regimen would result in serum peaks being substantially below 5 mg/l, which, for a population of extremely sick neonates, is decidedly unacceptable as the therapeutic efficacy of gentamicin is correlated to its peak concentration. 5 Given their results, a more appropriate recommendation for patients treated with HFOV might have been initiating therapy with 4 to 5 mg/kg/ dose every 24 hours as recommended by some, 6,7 and measuring both peak and trough levels after the first dose to arrive at optimal individualized dosing. An alternative and possibly better approach might be the use of a 5 to 7 mg/kg loading dose followed by once-daily dosing, 5,8 with appropriate serum level monitoring toDear Editor: The data presented by Drs.…”

“…5 Given their results, a more appropriate recommendation for patients treated with HFOV might have been initiating therapy with 4 to 5 mg/kg/ dose every 24 hours as recommended by some, 6,7 and measuring both peak and trough levels after the first dose to arrive at optimal individualized dosing. An alternative and possibly better approach might be the use of a 5 to 7 mg/kg loading dose followed by once-daily dosing, 5,8 with appropriate serum level monitoring toDear Editor: The data presented by Drs. Bhatt-Mehta and Donn have added to our knowledge of gentamicin pharmacokinetics in neonates undergoing high-frequency ventilation.…”

Community-acquired pneumonia: identification and evaluation of nonresponders

“…Furthermore, creatinine clearance, which generally correlates with clearance of several antibiotics [Lipman et al 2003], may also be increased, but commonly used formulas to compute it are useless [Baptista et al 2011]. Consequently, PK parameters measured in the healthy population may not correctly predict antibiotic concentrations in critically ill patients with sepsis, particularly at the early stages of severe pneumonia [Hansen et al 2001;Roberts and Lipman, 2006] and higher dosages may be needed [Pea and Viale, 2009]. Moreover, in critically ill patients with sepsis it has been suggested that larger antibiotic concentrations and time of exposure are necessary to achieve infection control [McKinnon et al 2008].…”