A global priority list of the TOp TEn resistant Microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis
Abstract
The World Health Organization (WHO) proposed a global priority pathogen list (PPL) of multidrug-resistant (MDR) bacteria. Our current objective was to provide global expert ranking of the most serious MDR bacteria present at intensive care units (ICU) that have become a threat in clinical practice. A proposal addressing a PPL for ICU, arising from the WHO Global PPL, was developed. Based on the supporting data, the pathogens were grouped in three priority tiers: critical, high, and medium. A multi-criteria decision analysis (MCDA) was used to identify the priority tiers. After MCDA, mortality, treatability, and cost of therapy were of highest concern (scores of 19/20, 19/20, and 15/20, respectively) while dealing with PPL, followed by healthcare burden and resistance prevalence. Carbapenem-resistant (CR) Acinetobacter baumannii, carbapenemase-expressing Klebsiella pneumoniae (KPC), and MDR Pseudomonas aeruginosa were identified as critical organisms. High-risk organisms were represented by CR Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae. Finally, ESBL Serratia marcescens, vancomycin-resistant Enterococci, and TMP-SMX-resistant Stenotrophomonas maltophilia were identified as medium priority. We conclude that education, investigation, funding, and development of new antimicrobials for ICU organisms should focus on carbapenem-resistant Gram-negative organisms.
Keywords
Multidrug-resistant bacteria Infection control Colonization Prevention Research Antimicrobials Intensive care SepsisNotes
Acknowledgements
We appreciate comments in the design from Nieves Larrosa, Barcelona, Spain. The study was developed in part from the Observership Programme, ESCMID, Basel, Switzerland (Vandana KE).
Funding
The study was funded in part by Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain, and Observership Programme from ESCMID, Basel, Switzerland.
Compliance with ethical standards
Competing interests
Dr. Rello served in the speaker’s bureau or consultant for Pfizer, Anchoagen, ROCHE. The remaining authors have no conflicts of interest to declare.
Ethical approval
Not required.
Supplementary material
References
- 1.De Waale J, Akova M, Antonelli M et al (2018) Antimicrobial resistance and antibiotic stewardship programs in the ICU: a position statement from ESICM/ESCMID/WAAAR round table on multidrug resistance. Intensive Care Med 44:189–196CrossRefGoogle Scholar
- 2.National efforts to combat antibiotic-resistant bacteria through science | NIH: National Institute of Allergy and Infectious Diseases n.d. https://www.niaid.nih.gov/news-events/national-efforts-combat-antibiotic-resistant-bacteria-through-science (Accessed Aug 2, 2018)
- 3.Tacconelli E, Carrara E, Savoldi A et al (2018) Discovery, research and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318–327CrossRefGoogle Scholar
- 4.Lucet JC, Koulenti D, Zahar JR (2014) Persistence of colonization with MDRO following discharge from the ICU. Intensive Care Med 40:603–605CrossRefGoogle Scholar
- 5.Sievert D, Ricks P, Edwards J, Schneider A, Patel J, Srinivasan A et al (2013) Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol 34:1–14CrossRefGoogle Scholar
- 6.Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281CrossRefGoogle Scholar
- 7.Otter JA, Mutters NT, Tacconelli E, Gikas A, Holmes AH (2015) Controversies in guidelines for the control of multidrug-resistant Gram-negative bacteria in EU countries. Clin Microbiol Infect 21:1057–1066CrossRefGoogle Scholar
- 8.WHO. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug resistant bacterial infections, including tuberculosis. Essent Med Heal Prod 2017:88. doi:WHO reference number: WHO/EMP/IAU/2017.12Google Scholar
- 9.Poulakou G, Matthaiou DK, Bassetti M, Erdem H, Dimopoulos G, Curcio DJ et al (2017) “Salvage treatment” for infections by extensively- and pan-drug-resistant pathogens is common and often sub-optimal. Intensive Care Med 43:1164–1166CrossRefGoogle Scholar
- 10.Zaragoza R, Ramirez P, Lopez-Pueyo MJ (2014) Nosocomial infections in intensive care units. Enferm Infecc Mircobiol Clin 32:320–327CrossRefGoogle Scholar
- 11.Borgatta B, Gattarello S, Mazo CA, Imbiscuso AT, Larrosa MN, Lujan M et al (2017) The clinical significance of pneumonia in patients with respiratory specimens harbouring multidrug-resistant Pseudomonas aeruginosa: a 5-year retrospective study following 5667 patients in four general ICUs. Eur J Clin Microbiol Infect Dis 36:2155–2163CrossRefGoogle Scholar
- 12.Grundmann H, Glasner C, Albiger B, Aanensen DM, Tomlinson CT, Andrasević AT et al (2017) Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis 17:153–163CrossRefGoogle Scholar
- 13.Kern WV (2018) Multidrug resistant bacteria: antibiotic prescription and antibiotics of last resort. DDtsch Med Wochenschr 143:643–650CrossRefGoogle Scholar
- 14.Micek ST, Wunderinck RG, Kollef MH et al (2015) An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care 19:219CrossRefGoogle Scholar
- 15.Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH (2014) Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care 18:596CrossRefGoogle Scholar
- 16.Paterson DL, Harris PNA (2015) Editorial Commentary: the new Acinetobacter equation: hypervirulence plus antibiotic resistance equals big trouble. Clin Infect Dis 61:155–156CrossRefGoogle Scholar
- 17.Health care-associated infections FACT SHEET. http://www.who.int/gpsc/country_work/gpsc_ccisc_fact_sheet_en.pdf. Accessed Nov 5th, 2018
- 18.Talaat M, El-Shokry M, El-Kholy J, Ismail G, Kotb S, Hafez S et al (2016) National surveillance of health care–associated infections in Egypt: developing a sustainable program in a resource-limited country. Am J Infect Control 44:1296–1301CrossRefGoogle Scholar
- 19.Lim C, Takahashi E, Hongsuwan M, Wuthiekanun V, Thamlikitkul V, Hinjoy S et al (2016) Epidemiology and burden of multidrug-resistant bacterial infection in a developing country. Elife 5. https://doi.org/10.7554/eLife.18082
- 20.Dondorp AM, Limmathurotsakul D, Ashley EA (2018) What’s wrong in the control of antimicrobial resistance in critically ill patients from low- and middle-income countries? Intensive Care Med 44:79–82CrossRefGoogle Scholar
- 21.Alp E, Damani N (2015) Healthcare-associated infections in intensive care units: epidemiology and infection control in low-to-middle income countries. J Infect Dev Ctries 9:1040–1045CrossRefGoogle Scholar
- 22.Iwuafor AA, Ogunsola FT, Oladele RO, Oduyebo OO, Desalu I, Egwuatu CC et al (2016) Incidence, clinical outcome and risk factors of intensive care unit infections in the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria. PLoS ONE 11:e0165242. https://doi.org/10.1371/journal.pone.0165242 CrossRefGoogle Scholar
- 23.Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH et al (1998) The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) study. EPIC international advisory committee. JAMA 274:639–644CrossRefGoogle Scholar
- 24.Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329. https://doi.org/10.1001/jama.2009.1754 CrossRefGoogle Scholar
- 25.Belton V, Stewart TJ (2002) Multiple criteria decision analysis: an integrated approach. Springer USGoogle Scholar