Inadequacy of standard aminoglycoside loading doses in acutely ill patients

Chelluri, Lakshmipathi; Jastremski, Michael S.

doi:10.1097/00003246-198712000-00015

Cited by 43 publications

(21 citation statements)

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“…In septic shock patients, inadequate serum concentrations for coverage of Pseudomonas during the first dosing interval have been shown for piperacillin–tazobactam, ceftazidime, cefepime, and meropenem using standard intermittent dosing 150 . Similarly, initial serum levels of aminoglycosides in septic patients are often inadequate resulting in inferior clinical outcomes 153 , 154 . Comparable finding have been reported for fluoroquinolones, 155 , 156 vancomycin, 152 , 157 teicoplanin, 158 and colistin 149 , 159 …”

Section: Loading Dosesmentioning

confidence: 98%

“…An emerging body of literature suggests that loading doses of some antimicrobials can potentially yield improved clinical outcomes 149 - 151 , 154 , 157 - 162 . Supportive data exists in severely ill patients including those with septic shock for aminoglycosides, 162 fluoroquinolones, 161 vancomycin, 152 , 157 teicoplanin, 158 and colistin 149 , 159 .…”

Section: Loading Dosesmentioning

confidence: 99%

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An alternate pathophysiologic paradigm of sepsis and septic shock

Kumar

2013

Virulence

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The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role.

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Section: Loading Dosesmentioning

confidence: 98%

Section: Loading Dosesmentioning

confidence: 99%

An alternate pathophysiologic paradigm of sepsis and septic shock

Kumar

2013

Virulence

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“…Perhaps most importantly with respect to initial empiric antimicrobial dosing is an increased volume of distribution for most antimicrobials, in part due to the rapid expansion of extracellular volume as a consequence of aggressive fluid resuscitation. This results in an unexpectedly high frequency of suboptimal drug levels with a variety of antimicrobials in patients with sepsis and septic shock [125][126][127][128]. Early attention to appropriate antimicrobial dosing is central to improving outcome given the marked increase in mortality and other adverse outcomes if there is a failure of rapid initiation of effective therapy.…”

mentioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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“…Dosage recommendations and microbiologic determination of the susceptibility of a bacterial strain to particular antibiotics are based on the assumption that the pharmacokinetics of the drug correspond to those of a "normal patient. " However, the distribution and elimination capacity of various antibiotic groups is highly variable in sepsis patents, and difficult to predict [189][190][191][192][193][194][195][196]. Although specialist societies such as the Paul Ehrlich Gesellschaft (PEG) or IDSA allow for this in their recommendations [153,178,183], these facts are still paid too little attention in clinical routine-with the effect of increased mortality in seriously ill patients [104,[197][198][199][200].…”

Section: Pharmacokinetic Conceptsmentioning

confidence: 99%