BACKGROUND: Antibiotic exposure in intensive care patients with sepsis is frequently inadequate and is associated with poorer outcomes. Antibiotic dosing is challenging in the intensive care, as critically ill patients have altered and fluctuating antibiotic pharmacokinetics that make current one-size-fits-all regimens unsatisfactory. Real-time bedside dosing software is not available yet, and therapeutic drug monitoring is typically used for few antibiotic classes and only allows for delayed dosing adaptation. Thus, adequate and timely antibiotic dosing continues to rely largely on the level of pharmacokinetic expertise in the ICU. Therefore, we set out to assess the level of knowledge on antibiotic pharmacokinetics among these intensive care professionals. METHODS: In May 2018, we carried out a cross-sectional study by sending out an online survey on antibiotic dosing to more than 20,000 intensive care professionals. Questions were designed to cover relevant topics in pharmacokinetics related to intensive care antibiotic dosing. The preliminary pass mark was set by members of the examination committee for the European Diploma of Intensive Care using a modified Angoff approach. The final pass mark was corrected for clinical relevance as assessed for each question by international experts on pharmacokinetics. RESULTS: A total of 1448 respondents completed the survey. Most of the respondents were intensivists (927 respondents, 64%) from 97 countries. Nearly all questions were considered clinically relevant by pharmacokinetic experts. The pass mark corrected for clinical relevance was 52.8 out of 93.7 points. Pass rates were 42.5% for intensivists, 36.1% for fellows, 24.8% for residents, and 5.8% for nurses. Scores without correction for clinical relevance were worse, indicating that respondents perform better on more relevant topics. Correct answers and concise clinical background are provided. CONCLUSIONS: Clinically relevant pharmacokinetic knowledge on antibiotic dosing among intensive care professionals is insufficient. This should be addressed given the importance of adequate antibiotic exposure in critically ill patients with sepsis. Solutions include improved education, intensified pharmacy support, therapeutic drug monitoring, or the use of real-time bedside dosing software. Questions may provide useful for teaching purposes.

Department of Anaesthesia and Intensive Care Medicine Kralovske Vinohrady University Hospital and The 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Clinical Pharmacology and Pharmacy Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Intensive Care Medicine Research VUmc Intensive Care Amsterdam UMC Location VUmc Vrije Universiteit Amsterdam Amsterdam The Netherlands

Intensive Care OLVG Amsterdam The Netherlands

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Fleischmann C, Scherag A, Adhikari NKJ, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med [Internet]. 2016 Feb 1 [cited 2018 Nov 22];193(3):259–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26414292. PubMed

Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States*. Crit Care Med [Internet]. 2013 May [cited 2018 Nov 22];41(5):1167–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23442987. PubMed

Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA [Internet]. 2014 Jul 2 [cited 2018 Nov 22];312(1):90. Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.5804 PubMed

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA [Internet]. 2016 Feb 23 [cited 2018 Nov 22];315(8):801. Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.0287 PubMed PMC

Asfar P, Meziani F, Hamel J-F, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med [Internet]. 2014 Apr 24 [cited 2018 Dec 5];370(17):1583–93. Available from: http://www.nejm.org/doi/10.1056/NEJMoa1312173 PubMed DOI

De Waele JJ, Lipman J, Akova M, Bassetti M, Dimopoulos G, Kaukonen M, et al. Risk factors for target non-attainment during empirical treatment with β-lactam antibiotics in critically ill patients. Intensive Care Med [Internet]. 2014 Sep 23 [cited 2018 Nov 22];40(9):1340–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25053248. PubMed

Abdul-Aziz MH, Lipman J, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, et al. Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort. J Antimicrob Chemother [Internet]. 2016 Jan [cited 2018 Nov 22];71(1):196–207. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26433783. PubMed

Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, et al. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis [Internet]. 2014 Apr 15 [cited 2018 Nov 22];58(8):1072–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24429437. PubMed

Ehmann L, Zoller M, Minichmayr IK, Scharf C, Maier B, Schmitt M V., et al. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study. Crit Care [Internet]. 2017 Dec 21 [cited 2018 Nov 26];21(1):263. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29058601. PubMed PMC

Zander J, Döbbeler G, Nagel D, Maier B, Scharf C, Huseyn-Zada M, et al. Piperacillin concentration in relation to therapeutic range in critically ill patients – a prospective observational study. Crit Care [Internet]. 2016 Dec 4 [cited 2018 Nov 26];20(1):79. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27039986. PubMed PMC

Khachman D, Conil J-M, Georges B, Saivin S, Houin G, Toutain P-L, et al. Optimizing ciprofloxacin dosing in intensive care unit patients through the use of population pharmacokinetic-pharmacodynamic analysis and Monte Carlo simulations. J Antimicrob Chemother [Internet]. 2011 Aug 1 [cited 2018 Nov 22];66(8):1798–809. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21653603. PubMed

van Zanten ARH, Polderman KH, van Geijlswijk IM, van der Meer GYG, Schouten MA, Girbes ARJ. Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study. J Crit Care [Internet]. 2008 Sep [cited 2018 Nov 22];23(3):422–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18725050. PubMed

Roberts JA, Abdul-Aziz H, Lipman JR, Mouton JW, Vinks AA, Felton TW, et al. Review Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis [Internet]. 2014 [cited 2018 Nov 22];14:498–509. Available from: http://dx.doi.org/10.1016/ PubMed PMC

Tabah A, De Waele J, Lipman J, Zahar JR, Cotta MO, Barton G, et al. The ADMIN-ICU survey: a survey on antimicrobial dosing and monitoring in ICUs. J Antimicrob Chemother [Internet]. 2015 Sep [cited 2019 Mar 29];70(9):2671–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26169558. PubMed

Roberts JA, Norris R, Paterson DL, Martin JH. Therapeutic drug monitoring of antimicrobials. Br J Clin Pharmacol [Internet]. 2012 Jan [cited 2018 Dec 4];73(1):27–36. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21831196. PubMed PMC

Ye Z-K, Tang H-L, Zhai S-D. Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis. Carvajal A, editor. PLoS One [Internet]. 2013 Oct 18 [cited 2018 Dec 4];8(10):e77169. Available from: https://dx.plos.org/10.1371/journal.pone.0077169 PubMed DOI PMC

Elbers PWG, Girbes A, Malbrain ML, Bosman R. Right dose, right now: using big data to optimize antibiotic dosing in the critically ill. Anestezjol Intens Ter [Internet]. 2014 Aug 4 [cited 2018 Nov 26];47(5):457–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26459228. PubMed

Wijnen-Meijer M, Burdick W, Alofs L, Burgers C, ten Cate O. Stages and transitions in medical education around the world: Clarifying structures and terminology. Med Teach [Internet]. 2013 Apr 29 [cited 2018 Nov 20];35(4):301–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23360484. PubMed

Bion J, Rothen HU. CRITICAL CARE PERSPECTIVE Models for intensive care training a European perspective. 2014 [cited 2018 Nov 20]; Available from: www.atsjournals.org PubMed

Gupta R, Zad O, Jimenez E. Analysis of the variations between Accreditation Council for Graduate Medical Education requirements for critical care training programs and their effects on the current critical care workforce. J Crit Care [Internet]. 2013 Dec [cited 2018 Nov 20];28(6):1042–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23890938. PubMed

CCSC Task Force on Critical Care Educational Pathways in Internal Medicine SM, Martin GS, Baumann MH, Curtis JR, Farmer JC, Fessler HE, et al. Training internists to meet critical care needs in the United States: a consensus statement from the Critical Care Societies Collaborative (CCSC). Crit Care Med [Internet]. 2014 May [cited 2018 Nov 20];42(5):1272–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24637881. PubMed PMC

I (Legislative acts) REGULATIONS Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation) (Text with EEA relevance) [Internet]. [cited 2019 Jan 6]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32016R0679&from=EN

Collaboration TC. Development of core competencies for an international training programme in intensive care medicine. Intensive Care Med [Internet]. 2006 Sep 14 [cited 2018 Nov 20];32(9):1371–83. Available from: http://link.springer.com/10.1007/s00134-006-0215-5 PubMed DOI

Berk RA. A consumer’s guide to setting performance standards on criterion-referenced tests [Internet]. Vol. 56, Hambleton & Eignor. Popham; 1986 [cited 2018 Nov 26]. Available from: https://journals.sagepub.com/doi/pdf/10.3102/00346543056001137 DOI

George S, Haque MS, Oyebode F. Standard setting: Comparison of two methods. BMC Med Educ [Internet]. 2006 Dec 14 [cited 2018 Nov 26];6(1):46. Available from: http://bmcmededuc.biomedcentral.com/articles/10.1186/1472-6920-6-46 PubMed DOI PMC

Jalili M, Hejri SM, Norcini JJ. Comparison of two methods of standard setting: the performance of the three-level Angoff method. Med Educ [Internet]. 2011 Dec 1 [cited 2018 Nov 26];45(12):1199–208. Available from: http://doi.wiley.com/10.1111/j.1365-2923.2011.04073.x PubMed DOI

Dwyer T, Wright S, Kulasegaram KM, Theodoropoulos J, Chahal J, Wasserstein D, et al. How to set the bar in competency-based medical education: standard setting after an Objective Structured Clinical Examination (OSCE). BMC Med Educ [Internet]. 2016 Dec 4 [cited 2018 Nov 26];16(1):1. Available from: http://www.biomedcentral.com/1472-6920/16/1 PubMed PMC

Shulruf B, Wilkinson T, Weller J, Jones P, Poole P. Insights into the Angoff method: results from a simulation study. BMC Med Educ [Internet]. 2016 May 4 [cited 2018 Nov 26];16:134. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27142788. PubMed PMC

PubMed PubReMiner: a tool for PubMed query building and literature mining [Internet]. [cited 2019 Jan 6]. Available from: https://hgserver2.amc.nl/cgi-bin/miner/miner2.cgi

Greenblatt DJ, Abourjaily PN. Core entrustables in clinical pharmacology: pearls for clinical practice pharmacokinetics and pharmacodynamics for medical students: a proposed course outline. J Clin Pharmacol [Internet]. 2016 [cited 2018 Dec 4];56(10):1180–95. Available from: https://accp1.onlinelibrary.wiley.com/doi/pdf/10.1002/jcph.732 PubMed DOI

Neuraz A, Guérin C, Payet C, Polazzi S, Aubrun F, Dailler F, et al. Patient mortality is associated with staff resources and workload in the ICU. Crit Care Med [Internet]. 2015 Aug [cited 2018 Dec 5];43(8):1587–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25867907. PubMed

Djulbegovic B, Guyatt GH. Progress in evidence-based medicine: a quarter century on. Lancet [Internet]. 2017 Jul 22 [cited 2018 Dec 5];390(10092):415–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28215660. PubMed

Syzdykova A, Malta A, Zolfo M, Diro E, Oliveira JL. Open-source electronic health record systems for low-resource settings: systematic review. JMIR Med Informatics [Internet]. 2017 Nov 13 [cited 2018 Dec 5];5(4):e44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29133283. PubMed PMC

Collier R. National Physician Survey: EMR use at 75%. Can Med Assoc J [Internet]. 2015 Jan 6 [cited 2018 Dec 5];187(1):E17–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25487665. PubMed PMC

Search - UpToDate [Internet]. [cited 2019 Jan 11]. Available from: https://www.uptodate.com/contents/search

Home | KNMP Kennisbank [Internet]. [cited 2019 Jan 11]. Available from: https://kennisbank.knmp.nl/

De Paepe P, Belpaire FM, Buylaert WA. Pharmacokinetic and pharmacodynamic considerations when treating patients with sepsis and septic shock. Clin Pharmacokinet [Internet]. 2002 [cited 2019 Jan 6];41(14):1135–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12405864. PubMed

Mahmoud SH, Shen C. Augmented renal clearance in critical illness: an important consideration in drug dosing. Pharmaceutics [Internet]. 2017 Sep 16 [cited 2019 Jan 6];9(3). Available from: http://www.ncbi.nlm.nih.gov/pubmed/28926966. PubMed PMC

Udy AA, Roberts JA, Shorr AF, Boots RJ, Lipman J. Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients. Crit Care [Internet]. 2013 Feb 28 [cited 2019 Jan 6];17(1):R35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23448570. PubMed PMC

Joynt GM, Lipman J, Gomersall CD, Young RJ, Wong ELY, Gin T. The pharmacokinetics of once-daily dosing of ceftriaxone in critically ill patients. J Antimicrob Chemother [Internet]. 2001 Apr 1 [cited 2019 Feb 6];47(4):421–9. Available from: https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/47.4.421 PubMed DOI