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Purpose: This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients.Methods: Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes.Results: TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients.Conclusion: Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide. [ABSTRACT FROM AUTHOR]

Purpose: This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients.Methods: Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes.Results: TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients.Conclusion: Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide. [ABSTRACT FROM AUTHOR]

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria. [ABSTRACT FROM AUTHOR]

Purpose: Clinical application of an antibiotic's pharmacokinetic/pharmacodynamic (PK/PD) properties may improve the outcome of severe infections. No data are available on the use of linezolid (LNZ) continuous infusion in critically ill obese patients affected by ventilator-associated pneumonia (VAP). Methods: We conducted a prospective randomized controlled trial to compare LNZ concentrations in plasma and epithelial lining fluid (ELF), when administered by intermittent and continuous infusion (II, CI), in obese critically ill patients affected by VAP. Results: Twenty-two critically ill obese patients were enrolled. At the steady state, in the II group, mean ± SD total and unbound maximum-minimum concentrations ( C/ C − C/C) were 10 ± 3.7/6.8 ± 2.6 mg/L and 1.7 ± 1.1/1.2 ± 0.8 mg/L, respectively. In the CI group, the mean ± SD total and unbound plasma concentrations ( C and C) were 6.2 ± 2.3 and 4.3 ± 1.6 mg/L, respectively. Within a minimum inhibitory concentration (MIC) range of 1-4 mg/L, the median (IQR) time LNZ plasma concentration persisted above MIC (% T > MIC) was significantly higher in the CI than the II group [100 (100-100) vs 100 (89-100), p = 0.05; 100 (100-100) vs 82 (54.8-98.8), p = 0.009; 100 (74.2-100) vs 33 (30.2-78.5), p = 0.005; respectively]. Pulmonary penetration (%) was higher in the CI group, as confirmed by a Monte Carlo simulation [98.8 (IQR 93.8-104.3) vs 87.1 (IQR 78.7-95.4); p < 0.001]. Conclusions: In critically ill obese patients affected by VAP, LNZ CI may overcome the limits of standard administration but these advantages are less evident with difficult to treat pathogens (MIC = 4 mg/L). These data support the usefulness of LNZ continuous infusion, combined with therapeutic drug monitoring (TDM), in selected critically ill populations. [ABSTRACT FROM AUTHOR]

Objective: To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis. Design: Open and prospective. Setting: Tertiary referral multi-disciplinary ICU. Patients: Twenty patients (two groups – group A: 3 months–1 year; group B 1–5 years). Interventions: Timed blood samples were taken for pharmacokinetics after the first dose (D0), as well as day 2 (D2) and then between days 6–8. Measurements and results: Ciprofloxacin serum levels were measured by high performance liquid chromatograghy. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (Cmax) for group A were D0 6.1±1.2 mg/l, D2 9.0±1.8 mg/l and D7 5.8±1.3 mg/l and, for group B, 7.4±1.3 mg/l, 7.8±1.6 mg/l and 6.4±1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (Cmin) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6±1.3, 19.2±1.63 and 14.1±1.4 mg/h per l, and group B: 15.9±1.3, 18.0±1.7 and 13.2±1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. Cmax in these patients were higher than the average Cmax. The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease. Conclusions: There was no accumulation of drug even after 7 days of administration. Our Cmax and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100–150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms. [ABSTRACT FROM AUTHOR]