Improving antibiotic dosing in special situations in the ICU

Jamal, Janattul-Ain; Economou, Caleb J.P.; Lipman, Jeffrey; Roberts, Jason A.

doi:10.1097/mcc.0b013e32835685ad

Cited by 90 publications

(21 citation statements)

References 71 publications

(73 reference statements)

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“…CRRT is by far the most common form of RRT in critically ill patients, although hybrid forms of RRT are increasingly common. The principles of antibiotic dosing during RRT and factors that need to be considered have been discussed in significant detail previously 56, 57 . In general, drugs with a high V d (> 1 L/kg), lipophilic drugs, and/or drugs with high protein binding (>80%) are poorly eliminated by RRT 56 .…”

Section: Challenge 1: the Effect Of Critical Illness Pathophysiology mentioning

confidence: 99%

Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions

Roberts

Abdul‐Aziz

Lipman

et al. 2014

The Lancet Infectious Diseases

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793

681

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Summary Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in sub-optimal outcomes. In this paper, we review the patient- and pathogen-related challenges that contribute to inadequate antibiotic dosing and discuss how a process for individualised antibiotic therapy, that increases the accuracy of dosing, can be implemented to further optimise care for the critically ill patient. The process for optimised antibiotic dosing firstly requires determination of the physiological derangements in the patient that can alter antibiotic concentrations including altered fluid status, microvascular failure, serum albumin concentrations as well as altered renal and hepatic function. Secondly, knowledge of the susceptibility of the infecting pathogen should be determined through liaison with the microbiology laboratory. The patient and pathogen challenges can then be solved by combining susceptibility data with measured antibiotic concentration data (where possible) into a clinical dosing software. Such software uses pharmacokinetic-pharmacodynamic (PK/PD) models from critically ill patients to accurately predict the dosing requirements for the individual patient with the aim of optimising antibiotic exposure and maximising effectiveness.

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Section: Challenge 1: the Effect Of Critical Illness Pathophysiology mentioning

confidence: 99%

Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions

Roberts

Abdul‐Aziz

Lipman

et al. 2014

The Lancet Infectious Diseases

Self Cite

793

681

View full text Add to dashboard Cite

show abstract

“…It is highly unlikely that this "one dose fits all" strategy will maximize antibiotic effectiveness in all patients. Unpredictable drug concentrations in plasma and other body compartments due to altered volume of distribution and clearance may result from factors as diverse as acute pathophysiology during critical care admission (such as sepsis and immuno-suppression), obesity [10], early ages [11], advanced age, surgical prophylaxis for longer invasive procedures [12], cystic fibrosis [13], the use of techniques for organ replacement in case of organ failure (extracorporeal membrane oxygenation (ECMO)) and renal replacement therapy (RRT) [14,15]. To add to these significant alterations of PK in critically ill patients, the PD target might be different depending on the indications.…”

Section: Sub-optimal Antibiotic Exposure In High-risk Patient Groupsmentioning

confidence: 99%

Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

Mabilat

Gros

Nicolau

et al. 2019

Eur J Clin Microbiol Infect Dis

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Therapeutic drug monitoring (TDM) of antibiotics has been practiced for more than half a century, but it is still not widely applied for infected patients. It has a traditional focus on limiting toxicity of specific classes of antibiotics such as aminoglycosides and vancomycin. With more patients in critical care with higher levels of sickness severity and immunosuppression as well as an increasingly obese and ageing population, an increasing risk of suboptimal antibiotic exposure continues to escalate. As such, the value of TDM continues to expand, especially for beta-lactams which constitute the most frequently used antibiotic class. To date, the minimum inhibitory concentration (MIC) of infectious microbes rather than classification in terms of susceptible and resistant can be reported. In parallel, increasingly sophisticated TDM technology is becoming available ensuring that TDM is feasible and can deliver personalized antibiotic dosing schemes. There is an obvious need for extensive studies that will quantify the improvements in clinical outcome of individual TDM-guided dosing. We suggest that a broad diagnostic and medical investigation of the TDM arena, including market analyses and analytical technology assessment, is a current priority.

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“…Inadequate drug exposure is one of the primary reasons why the mortality rate in patients with sepsis or septic shock has not decreased significantly over the last 10 years [6]. In particular, hydrophilic drugs, such as beta-lactam antibiotics, show profound pharmacokinetic and pharmacodynamic variability in critical illness due to capillary leakage and altered physiological conditions [7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

et al. 2020

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Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

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Improving antibiotic dosing in special situations in the ICU

Abstract: In the context of such variable pharmacokinetics, a guideline approach to dosing remains elusive because of insufficient available data and, therefore, use of therapeutic drug monitoring should be considered advantageous where possible.

Cited by 90 publications

References 71 publications

Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions

Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions

Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

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