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Ampicillin and Amoxicillin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Alasdair M. Geddes, Ian M. Gould, Jason A. Roberts, M. Lindsay Grayson, Sara E. Cosgrove
Some critically ill patients, such as those managed in the intensive care unit, can develop augmented renal clearance (defined as a creatinine clearance exceeding 130 mL/min), whereby renally cleared penicillins may be subject to higher than expected drug clearances and result in very low trough concentrations (Udy et al., 2012). In these patients, more frequent dosing of AMP–AMOX is suggested to ensure target concentrations are achieved, although there are no formal protocols to guide clinicians.
A nationwide evaluation of antibiotics consumption in Swedish intensive care units
Published in Infectious Diseases, 2022
Fredrik Sjövall, Morgan Edström, Sten Walther, Håkan Hanberger
DDD does not necessarily correspond to the prescribed daily dose. Individual patients, such as the obese or patients at risk of underdosing due to augmented renal clearance can be prescribed higher doses. Conversely, in patients with renal failure, the dose will be reduced to compensate for reduced clearance. We had no information regarding such adjustments. The DDD data were derived from deliveries from the pharmacies to the ICUs which is a proxy of consumption. The relationship between sales and consumption has previously been described as acceptable and can thus serve as an accessible marker for consumption [24,25]. Perioperative care is integrated to a greater or lesser extent in different ICUs and some of the variation seen in our results likely reflects not only antibiotics used for treatment but also for prophylaxis. Beta-lactamase resistant penicillins (J1CF) are most frequently used for prophylaxis in Sweden. As a sensitivity analysis, all results were calculated with and without the inclusion of J01CF which did not alter any of the main conclusions except that the most commonly used class was then penicillins with betalactamase inhibitors. We used hospital category and SAPS3 as indicators of case mix [26]. SAPS3 is well correlated with outcome and has been customised to Swedish ICUs [27]. Even so, SAPS3 does not cover all case mix factors which might influence the use of antibiotics.
Comparing the pharmacokinetics and organ/tissue distribution of anti-methicillin-resistant Staphylococcus aureus agents using a rat model of sepsis
Published in Xenobiotica, 2022
Shinji Kobuchi, Naoya Kanda, Taichi Okumi, Yuma Kano, Himawari Tachi, Yukako Ito, Toshiyuki Sakaeda
Sepsis is a major cause of death in critically ill patients (Fleischmann et al. 2016). The selection and dosage of antimicrobial agents for treating sepsis or septic shock in individual patients are important for achieving favourable clinical outcomes (Egi et al. 2021); however, sepsis-derived physiological changes make this process difficult. Fluid volume changes caused by capillary leakage, fluid therapy, hypoalbuminemia, and altered protein binding of drugs change the drug distribution volume. Moreover, augmented renal clearance caused by increased cardiac output and renal blood flow is well-documented (Roberts and Lipman 2009; Udy et al. 2011; Egi et al. 2021). These physiological changes are critical for the large inter-individual variations in the pharmacokinetics of antimicrobial agents.
Antimicrobial safety considerations in critically ill patients: part I: focused on acute kidney injury
Published in Expert Review of Clinical Pharmacology, 2022
Foroud Shahbazi, Lida Shojaei, Fakhrossadat Farvadi, Sara Kadivarian
Early initiation of appropriate antimicrobial agents at the correct dose is a challenging issue for critical ill patients. As the Vd of hydrophilic antibiotics is changed, no dose adjustment is required in the first 24 hours or inpatients with transient AKI. Pharmacodynamic target attainment is essential to increase the probability of clinical and microbiological cure and prevent resistance development. Although previous clinical trials have used Cmax/MIC of 40–60% for beta-lactams, but recent studies proposed a higher target. TDM of beta-lactam antibiotics with Cmax/MIC = 4–8 fT > 100% is proposed to optimize treatment and overcome resistance development. However, further prospective studies are needed to confirm these pharmacodynamic targets. The FDA-approved doses for some antibiotics may not be adequate to achieve pharmacodynamic targets, especially in patients with ARC. Monitoring of patients who have criteria for augmented renal clearance (including sepsis, trauma, surgery, febrile neutropenia, cystic fibrosis, pregnancy, burns, and young patients (<50 years)) is recommended in ICU patients. Some patients with transient AKI or those in stage 1 of AKI may have augmented renal clearance when measuring CrCl using 1–8 hours urine collection. Therefore, clinician should be aware about this population that may need higher antimicrobial doses to achieve the antibiotics target.