Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

Shah, Snehal; Barton, Greg; Fischer, Andréas

doi:10.1177/1751143714564816

Cited by 58 publications

(50 citation statements)

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“…The misuse of antimicrobial medicines accelerates the natural evolution of resistant strains and encourages the spread of AMR. Previous studies have reported that therapeutic failure and negative clinical outcomes emanate from subtherapeutic doses of antibiotics, which leads to the development of antibiotic resistance if suitable adjustments to the dose are not made (Shah et al, 2015, Roberts et al, 2008. In today's clinical trials, biochemical and genetic mechanisms of resistance are demonstrated by most bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

Munyeza

Shobo

Baijnath

et al. 2015

Biomedical Chromatography

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Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 µm) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright © 2015 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

Munyeza

Shobo

Baijnath

et al. 2015

Biomedical Chromatography

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“…Antibiotic target sites[8].Pharmacokinetics (PK) refers to the study of concentration changes of a drug over a period of time. After the administration of a drug, drugs undergoes ADME (absorption, distribution, metabolism and excretion) processes that condition the kinetics of the drug and the concentration-time profile, which may be characterized by the PK parameters, such as total body clearance, volume of distribution, protein binding or bioavailability[30,31].Pharmacokinetics of antibioticsAminoglycosides route of administered is majorly via parenteralexcept cases of intestinal infections or indication for decontamination. aminoglycosides upon absorption into the bloodstream, they have low volume of distribution (<0.3 L/kg) thus aminoglycosides are mainly distributed in blood plasma.…”

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confidence: 99%

Antibiotics and Drug Pharmacology

Adefegha¹

2019

Act Scie Pharma

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Drugs are chemicals which when administered to living organisms produce a biological effect. The term antibiotic was derived from the word "antibiosis", which literally means "against life". Antibiotics, in the past, were considered to be organic compounds produced by one microorganism which are toxic to other microorganisms by selectively killing or inhibiting the growth of other microorganisms [1]. In modern terms, this definition includes antimicrobials produced through synthetic means partly (semi-synthetic) or wholly (synthetic) [2]. Some antibiotics are able to kill bacteria completely while some only inhibit their growth. Bactericidal are those that kill bacteria while bacteriostatic are those that inhibit bacterial growth [3]. In September 1928, the first antibiotics (Penicillin) was accidentally discovered from a soil inhabiting fungus Penicillium notatum by late Sir Alexander Fleming, an English Bacteriologist, but its discovery was first reported in 1929 [4], it was purified in 1940 by Florey and Chain, who purified it by freeze drying and a Nobel prize was won in 1945. Clinical trials were first conducted on humans in 1940 and during World War II, penicillin saved 12-15% of lives [1,5]. Selman Waksman discovered Streptomycin in 1943 which is active against all Gram-negatives and it is the first antibiotic active against Mycobacterium tuberculosis. Most severe infections are caused by gram-negatives and Mycobacterium tuberculosis.

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“…34,35 Therefore, obese individuals may have poorer peripheral perfusion, resulting in lower subcutaneous adipose tissue concentrations of antimicrobials. 35 Oedema combined with fluid resuscitation in critically ill obese patients can further increase the Vd of different antimicrobials 14 (Figure 2-2).…”

Section: Effects Of Obesity On Drug Distributionmentioning

confidence: 99%

“…7 [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] (n = 38) Of interest, the statistical significance of obesity for affecting PK/PD target attainment for piperacillin in the univariate analysis was not found to be significant in the logistic regression (Table 3 -5). The factors associated with achieving the lower PK/PD target, 100% fT>MIC, for both antibiotics included use of prolonged infusion, a lower CLCR defined as ≤ 100 mL/min and increasing age.…”

Section: Clcr > 50 To ≤ 100mentioning

confidence: 99%

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An investigation of the pharmacokinetics of piperacillin, meropenem and fluconazole in critically ill obese patients

Alobaid¹

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The increasing numbers of critically ill obese patients in the intensive care unit (ICU) and the high frequency of antimicrobial prescription in these patients present a challenge for prescribing effective antimicrobial doses. Critically ill obese patients have greater infectionrelated morbidity and mortality than their non-obese counterparts. The underlying explanation for these inferior outcomes remains unclear, although sub-optimal antimicrobial dosing may be a contributing factor. Unfortunately there is a paucity of research and no recognised guidelines to assist clinicians with dosing antimicrobials in these patients who commonly develop dramatic physiological changes that can lead to significantly altered drug concentrations, and therefore, sub-optimal treatment.Critical illness pathologies, such as sepsis and septic shock are reported to alter the pharmacokinetics of many antimicrobials, including piperacillin, meropenem and fluconazole. Along with the alterations in the pharmacokinetics of these agents caused by obesity, sub-therapeutic concentrations of these drugs are likely in critically ill obese patients.This Thesis addresses the limitations of current knowledge by describing the plasma pharmacokinetics of piperacillin, meropenem and fluconazole in critically ill non-obese, obese and morbidly obese patients. The Thesis then provides dosing recommendations which can be used for more effective antibiotic dosing.Firstly a structured review of the effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients was performed. The review concluded that the presence of obesity augments the pharmacokinetic changes of antimicrobials in critical illness. Furthermore, this chapter also provides suggested dosing regimens for use in critically ill obese patients based on the published literature.To investigate the effect of obesity on antimicrobial trough concentrations and achievement of target exposures in obese and non-obese critically ill patients, a large retrospective study (n = 1400) of therapeutic drug monitoring data of piperacillin and meropenem was performed. This study found that piperacillin concentrations were significantly affected by the presence of obesity, with no significant differences evident for meropenem. IIITo further explore the effect of obesity using a more descriptive approach, prospective pharmacokinetic studies were conducted with piperacillin/ tazobactam (n=37), meropenem (n=19) and fluconazole (n=21) in critically ill patients across different body mass index (BMI) classifications including non-obese (BMI 18.5 -29.9 kg/m 2 ), obese kg/m 2 ), and morbidly-obese (BMI ≥ 40 kg/m 2 ). The included patients had widely varying BMIs, but typical age and sex distributions as encountered in ICUs. Using a population pharmacokinetic modelling approach, it was concluded that BMI only had a small effect on antimicrobial volume of distribution, whilst measured creatinine clearance had a significant effect on drug clearance. Using Monte Carlo dosing simulations, it...

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Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

Cited by 58 publications

References 27 publications

Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

Development and validation of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the quantification of tigecycline in rat brain tissues

Antibiotics and Drug Pharmacology

An investigation of the pharmacokinetics of piperacillin, meropenem and fluconazole in critically ill obese patients

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