Publications (3) View all
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Article: Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review.
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ABSTRACT: The prevalence of invasive fungal infections (IFIs) caused by Candida spp. is increasing in critically ill patients. Recent development of new antifungal agents has significantly contributed to the successful treatment of IFIs. However, the pharmacokinetics of antifungal agents can be altered in a number of disease states, including critical illness. Therefore, doses established in healthy volunteers and other patient groups may not be appropriate for the critically ill. Moreover, inadequate dosing may contribute to treatment failure and the emergence of resistance. This systematic review provides a critical analysis of the pharmacokinetics of antifungal agents in the critically ill and their relevance to dosing requirements in clinical practice. Based on the limited data available, dosing of some antifungal agents may have to be adjusted in critically ill patients with conserved renal function as well as in those requiring renal replacement therapy. Further research to confirm the appropriateness of current dosing strategies to attain the appropriate pharmacodynamic targets is recommended.International journal of antimicrobial agents 09/2011; 39(1):1-10. · 3.03 Impact Factor -
Article: Pharmacokinetic evaluation of fluconazole in critically ill patients.
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ABSTRACT: INTRODUCTION: Invasive candidiasis has emerged over the last few decades as an increasingly important nosocomial problem for the critically ill, affecting around 2% of intensive care unit patients. Although poor outcomes associated with invasive candidiasis among critically ill patients may relate to severe underlying disease processes and delayed institution of antifungal therapy, inadequate dosing of antifungal agents may also contribute. AREAS COVERED: This drug evaluation provides a critical appraisal of the published literature pertaining to the pharmacokinetics of fluconazole in critically ill, obese or severely burned patients, including those receiving acute renal replacement therapy. The pharmacodynamics of fluconazole is also covered, as well as the likely clinical implications for optimal dosing and the toxicity of fluconazole. Last, variations in fluconazole susceptibility patterns of Candida spp. are also discussed. EXPERT OPINION: Recently, there has been an increased but geographically variable prevalence of non-albicans Candida spp., causing invasive candidiasis and an overall trend towards reduced fluconazole susceptibility. The pathophysiological changes of critical illness, coupled with a lack of dose finding studies, support the use of local susceptibility patterns to guide fluconazole dosing until such time as pharmacokinetic-pharmacodynamic information to guide optimal fluconazole dosing strategies and pharmacodynamic targets becomes available.Expert Opinion on Drug Metabolism & Toxicology 09/2011; 7(11):1431-40. · 3.12 Impact Factor -
Article: β-Lactam pharmacokinetics and pharmacodynamics in critically ill patients and strategies for dose optimization: a structured review.
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ABSTRACT: 1. Infections and related sepsis are two of the most prevalent issues in the care of critically ill patients, with mortality as high as 70%. Appropriate antibiotic selection, as well as adequate dosing, is important to improve the clinical outcome for these patients. 2. β-Lactams are the most common antibiotic class used in critically ill sepsis patients because of their broad spectrum of activity and high tolerability. β-Lactams exhibit time-dependent antibacterial activity. Therefore, concentrations need to be maintained above the minimum inhibitory concentration (MIC) of pathogenic bacteria. β-Lactams are hydrophilic antibiotics with small distribution volumes similar to extracellular water and are predominantly excreted through the renal system. 3. Critically ill patients experience a myriad of physiological changes that result in changes in the pharmacokinetics (PK) of hydrophilic drugs such as β-lactams. A different approach to dosing with β-lactams may increase the likelihood of positive outcomes considering the pharmacodynamics (PD) of β-lactams, as well as the changes in PK in critically ill patients. 4. The present review describes the strategies for dose optimization of β-lactams in critically ill patients in line with the PK and PD of these drugs.Clinical and Experimental Pharmacology and Physiology 04/2012; 39(6):489-96. · 1.85 Impact Factor
