Optimising the administration of antibiotics in critically ill patients

Abstract

Optimal outcome and a reduction in the potential for resistance require that appropriate pharmacokinetic (PK) targets are achieved. Consequently, we need to target drug concentrations that are significantly higher than those conventionally presumed to be adequate.Drug exposure varies according to the molecular weight, degree of ionisation, protein binding and lipid solubility of each agent. In critically ill patients, hypoalbuminaemia increases the free fraction of hydrophilic drugs, which in turn increases the volume of distribution and clearance (CL), both of which result in reduced drug levels. Similarly, augmented renal clearance (ARC), defined as a creatinine clearance (CLcr) of >130 mL/min/1.73 m 2 , which occurs frequently in critically ill patients, particularly younger patients with normal or near-normal creatinine levels, may also significantly reduce drug exposure. Studies have demonstrated a greater mortality and lower cure with ARC, particularly with the additive effects of obesity, hypoalbuminaemia and increasing resistance, if conventional dosages are used. These concepts apply to antibiotics targeting Gram-negative and -positive organisms. Knowledge of PK and the resistance profiles of organisms in each environment is necessary to prescribe appropriately. This article discusses these issues and the doses that should be used.

Opportunities to optimise colistin stewardship in hospitalised patients in South Africa: Results of a multisite utilisation audit

“…This demonstrates a lack of understanding regarding the need for appropriate loading doses, which should be in the region of 9 -12 MU regardless of renal function. [9,19] The findings of our study further emphasise the importance of ensuring optimal dosing as, although Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were not available so that patients could be appropriately matched, higher loading doses appeared to be associated with shorter duration of treatment. Interestingly, there also appeared to be an association with the manner in which the maintenance doses were administered.…”

Usage of antibiotics in the intensive care units of an academic tertiary-level hospital

“…The rationale for higher doses is related to the lower than expected drug concentrations in critically ill patients. 20 Plasma concentrations of hydrophilic antibiotics may be decreased owing to the increased volume of distribution due to capillary leak, the reduced albumin (for highly protein bound drugs) and fluid overload. In addition augmented renal clearance (ARC) due to increased cardiac output from use of inotropes, and renal replacement therapy 21 may contribute.…”

“…Thursky et al 24 found that the implementation of a computerised system, incorporating the microbiology and a decision system, assisted in reducing the use of unnecessary broad-spectrum agents. Similarly, obtaining timeous and appropriate specimens prior to initiating antibiotic treatment is critical 20 in ensuring the correct antibiotic choice and facilitating de-escalation. In CMJAH future studies need to be cognisant of these fundamental principles.…”

Uji Aktivitas Antibakteri Ekstrak Kasar Umbi Sarang Semut (Myrmecodia pendens) Dibanding dengan Klorheksidin terhadap Streptococcus sanguinis

“…9 Efek antibakteri yang optimal dari antibakteri concentrationdependent bergantung pada luas area di bawah kurva penghambatan yang disederhanakan menjadi rasio antara konsentrasi optimal bila dibanding dengan MIC antibakteri tersebut. 10 Pada penelitian ini diketahui efek antibakteri paling optimal dihasilkan pada konsentrasi 39,06 ppm. Hal ini belum dapat dipastikan karena pada penelitian ini pengujian konsentrasi di atas 39,06 ppm, yaitu pada konsentrasi 78,13 ppm dipengaruhi oleh sifat kekeruhan yang dimiliki oleh ekstrak kasar sehingga perhitungan persentase kematian sel bakteri tidak dapat dilakukan.…”