Semin Respir Crit Care Med 2022; 43(01): 141-149
DOI: 10.1055/s-0041-1741014
Review Article

Antibiotic Decision-Making in the ICU

Luis Parra-Rodriguez
1   Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
,
M. Cristina Vazquez Guillamet
1   Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
2   Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
› Author Affiliations

Abstract

It is well established that Intensive Care Units (ICUs) are a focal point in antimicrobial consumption with a major influence on the ecological consequences of antibiotic use. With the high prevalence and mortality of infections in critically ill patients, and the clinical challenges of treating patients with septic shock, the impact of real life clinical decisions made by intensivists becomes more significant. Both under- and over-treatment with unnecessarily broad spectrum antibiotics can lead to detrimental outcomes. Even though substantial progress has been made in developing rapid diagnostic tests that can help guide antibiotic use, there is still a time window when clinicians must decide the empiric antibiotic treatment with insufficient clinical data. The continuous streams of data available in the ICU environment make antimicrobial optimization an ongoing challenge for clinicians but at the same time can serve as the input for sophisticated models. In this review, we summarize the evidence to help guide antibiotic decision-making in the ICU. We focus on 1) deciding if to start antibiotics, 2) choosing the spectrum of the empiric agents to use, and 3) de-escalating the chosen empiric antibiotics. We provide a perspective on the role of machine learning and artificial intelligence models for clinical decision support systems that can be incorporated seamlessly into clinical practice in order to improve the antibiotic selection process and, more importantly, current and future patients' outcomes.



Publication History

Article published online:
16 February 2022

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  • References

  • 1 Vincent JL, Bihari DJ, Suter PM. et al; EPIC International Advisory Committee. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. JAMA 1995; 274 (08) 639-644
  • 2 Society of Critical Care Medicine. Critical Care Statistics. Accessed on October 15, 2021 at: https://www.sccm.org/Communications/Critical-Care-Statistics
  • 3 Rhee C, Jones TM, Hamad Y. et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals. JAMA Netw Open 2019; 2 (02) e187571
  • 4 Kadri SS, Rhee C, Strich JR. et al. Estimating ten-year trends in septic shock incidence and mortality in United States Academic Medical Centers using clinical data. Chest 2017; 151 (02) 278-285
  • 5 Rhodes A, Evans LE, Alhazzani W. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43 (03) 304-377
  • 6 Kalil AC, Metersky ML, Klompas M. et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63 (05) e61-e111
  • 7 Seymour CW, Gesten F, Prescott HC. et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376 (23) 2235-2244
  • 8 Kumar A, Roberts D, Wood KE. et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34 (06) 1589-1596
  • 9 Vazquez-Grande G, Kumar A. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy. Semin Respir Crit Care Med 2015; 36 (01) 154-166
  • 10 Versporten A, Zarb P, Caniaux I. et al; Global-PPS network. Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries: results of an internet-based global point prevalence survey. Lancet Glob Health 2018; 6 (06) e619-e629
  • 11 Timsit JF, Bassetti M, Cremer O. et al. Rationalizing antimicrobial therapy in the ICU: a narrative review. Intensive Care Med 2019; 45 (02) 172-189
  • 12 The review on antimicrobial resistance team chaired by O'Neil J. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Review on Antimicrobial Resistance 2014. Accessed on October 15, 2021 at: https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf
  • 13 CDC. Antibiotic resistance threats in the United States, 2019. Accessed on October 15, 2021 at: https://www.cdc.gov/drugresistance/biggest-threats.html
  • 14 Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother 2010; 54 (11) 4851-4863
  • 15 Vazquez-Guillamet C, Scolari M, Zilberberg MD, Shorr AF, Micek ST, Kollef M. Using the number needed to treat to assess appropriate antimicrobial therapy as a determinant of outcome in severe sepsis and septic shock. Crit Care Med 2014; 42 (11) 2342-2349
  • 16 Rhee C, Kadri SS, Dekker JP. et al; CDC Prevention Epicenters Program. Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use. JAMA Netw Open 2020; 3 (04) e202899
  • 17 Brown KA, Jones M, Daneman N. et al. Importation, antibiotics, and clostridium difficile infection in veteran long-term care: a multilevel case-control study. Ann Intern Med 2016; 164 (12) 787-794
  • 18 Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 2011; 53 (01) 42-48
  • 19 Rhee C, Kadri SS, Danner RL. et al. Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Crit Care 2016; 20: 89
  • 20 Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med 2015; 372 (17) 1629-1638
  • 21 Klein Klouwenberg PM, Cremer OL, van Vught LA. et al. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care 2015; 19 (01) 319
  • 22 Denny KJ, De Waele J, Laupland KB, Harris PNA, Lipman J. When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit. Clin Microbiol Infect 2020; 26 (01) 35-40
  • 23 Denny KJ, Cotta MO, Parker SL, Roberts JA, Lipman J. The use and risks of antibiotics in critically ill patients. Expert Opin Drug Saf 2016; 15 (05) 667-678
  • 24 Hranjec T, Rosenberger LH, Swenson B. et al. Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis 2012; 12 (10) 774-780
  • 25 Bauer KA, Perez KK, Forrest GN, Goff DA. Review of rapid diagnostic tests used by antimicrobial stewardship programs. Clin Infect Dis 2014; 59 (Suppl. 03) S134-S145
  • 26 Bostwick AD, Jones BE, Paine R, Goetz MB, Samore M, Jones M. Potential impact of hospital-acquired pneumonia guidelines on empiric antibiotics. an evaluation of 113 veterans affairs medical centers. Ann Am Thorac Soc 2019; 16 (11) 1392-1398
  • 27 Daneman N, Low DE, McGeer A, Green KA, Fisman DN. At the threshold: defining clinically meaningful resistance thresholds for antibiotic choice in community-acquired pneumonia. Clin Infect Dis 2008; 46 (08) 1131-1138
  • 28 Diamant M, Baruch S, Kassem E. et al. A game theoretic approach reveals that discretizing clinical information can reduce antibiotic misuse. Nat Commun 2021; 12 (01) 1148
  • 29 Shortliffe EH. Computer-Based Medical Consultation. MYCIN. New York, NY: Elsevier; 1976
  • 30 Viasus D, Puerta-Alcalde P, Cardozo C. et al. Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection. Clin Microbiol Infect 2020; 26 (03) 345-350
  • 31 Garcia-Vidal C, Cardozo-Espinola C, Puerta-Alcalde P. et al. Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance. PLoS One 2018; 13 (06) e0199531
  • 32 Goodman KE, Lessler J, Cosgrove SE. et al; Antibacterial Resistance Leadership Group. A clinical decision tree to predict whether a bacteremic patient is infected with an extended-spectrum β-lactamase-producing organism. Clin Infect Dis 2016; 63 (07) 896-903
  • 33 Vazquez-Guillamet MC, Vazquez R, Micek ST, Kollef MH. Predicting resistance to piperacillin-tazobactam, cefepime and meropenem in septic patients with bloodstream infection due to gram-negative bacteria. Clin Infect Dis 2017; 65 (10) 1607-1614
  • 34 MacFadden DR, Coburn B, Shah N. et al. Decision-support models for empiric antibiotic selection in gram-negative bloodstream infections. Clin Microbiol Infect 2019; 25 (01) 108.e1-108.e7
  • 35 Peiffer-Smadja N, Rawson TM, Ahmad R. et al. Machine learning for clinical decision support in infectious diseases: a narrative review of current applications. Clin Microbiol Infect 2020; 26 (05) 584-595
  • 36 Macesic N, Polubriaginof F, Tatonetti NP. Machine learning: novel bioinformatics approaches for combating antimicrobial resistance. Curr Opin Infect Dis 2017; 30 (06) 511-517
  • 37 Tsoukalas A, Albertson T, Tagkopoulos I. From data to optimal decision making: a data-driven, probabilistic machine learning approach to decision support for patients with sepsis. JMIR Med Inform 2015; 3 (01) e11
  • 38 Pyayt A, Khan R, Brzozowski R, Eswara P, Gubanov M. “Rapid Antibiotic Susceptibility Analysis Using Microscopy and Machine Learning.” Paper presented at: 2020 IEEE International Conference on Big Data (Big Data); 2020: 5804-5806
  • 39 Wolff RF, Moons KGM, Riley RD. et al; PROBAST Group†. PROBAST: a tool to assess the risk of bias and applicability of prediction model studies. Ann Intern Med 2019; 170 (01) 51-58
  • 40 Grobbee DE, Hoes AW. Clinical Epidemiology: Principles, Methods, and Applications for Clinical Research. London: Jones & Bartlett; 2009
  • 41 Begg CB, McNeil BJ. Assessment of radiologic tests: control of bias and other design considerations. Radiology 1988; 167 (02) 565-569
  • 42 Ragland DR. Dichotomizing continuous outcome variables: dependence of the magnitude of association and statistical power on the cutpoint. Epidemiology 1992; 3 (05) 434-440
  • 43 van der Ploeg T, Austin PC, Steyerberg EW. Modern modelling techniques are data hungry: a simulation study for predicting dichotomous endpoints. BMC Med Res Methodol 2014; 14: 137
  • 44 Moons KG, Altman DG, Vergouwe Y, Royston P. Prognosis and prognostic research: application and impact of prognostic models in clinical practice. BMJ 2009; 338: b606
  • 45 Colman AM, Krockow EM, Chattoe-Brown E, Tarrant C. Medical prescribing and antibiotic resistance: a game-theoretic analysis of a potentially catastrophic social dilemma. PLoS One 2019; 14 (04) e0215480
  • 46 Vazquez Guillamet C, Kollef MH. Acinetobacter pneumonia: improving outcomes with early identification and appropriate therapy. Clin Infect Dis 2018; 67 (09) 1455-1462
  • 47 Huang AM, Newton D, Kunapuli A. et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis 2013; 57 (09) 1237-1245
  • 48 Timbrook TT, Morton JB, McConeghy KW, Caffrey AR, Mylonakis E, LaPlante KL. The effect of molecular rapid diagnostic testing on clinical outcomes in bloodstream infections: a systematic review and meta-analysis. Clin Infect Dis 2017; 64 (01) 15-23
  • 49 Gomes Silva BN, Andriolo RB, Atallah AN, Salomão R. De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock. Cochrane Database Syst Rev 2010; 12 (12) CD007934
  • 50 Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A. et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 2014; 40 (01) 32-40
  • 51 De Bus L, Depuydt P, Steen J. et al; DIANA study group. Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study. Intensive Care Med 2020; 46 (07) 1404-1417
  • 52 de Jong E, van Oers JA, Beishuizen A. et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016; 16 (07) 819-827
  • 53 Huang HB, Peng JM, Weng L, Wang CY, Jiang W, Du B. Procalcitonin-guided antibiotic therapy in intensive care unit patients: a systematic review and meta-analysis. Ann Intensive Care 2017; 7 (01) 114
  • 54 Huang SS, Septimus E, Kleinman K. et al; CDC Prevention Epicenters Program, AHRQ DECIDE Network and Healthcare-Associated Infections Program. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 2013; 368 (24) 2255-2265
  • 55 Bradley CW, Wilkinson MA, Garvey MI. The effect of universal decolonization with screening in critical care to reduce MRSA across an entire hospital. Infect Control Hosp Epidemiol 2017; 38 (04) 430-435
  • 56 Huang SS, Septimus E, Avery TR. et al. Cost savings of universal decolonization to prevent intensive care unit infection: implications of the REDUCE MRSA trial. Infect Control Hosp Epidemiol 2014; 35 (Suppl. 03) S23-S31
  • 57 Davis KA, Stewart JJ, Crouch HK, Florez CE, Hospenthal DR. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection. Clin Infect Dis 2004; 39 (06) 776-782
  • 58 Dangerfield B, Chung A, Webb B, Seville MT. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother 2014; 58 (02) 859-864
  • 59 Mergenhagen KA, Starr KE, Wattengel BA, Lesse AJ, Sumon Z, Sellick JA. Determining the utility of methicillin-resistant Staphylococcus aureus nares screening in antimicrobial stewardship. Clin Infect Dis 2020; 71 (05) 1142-1148
  • 60 Sarikonda KV, Micek ST, Doherty JA, Reichley RM, Warren D, Kollef MH. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med 2010; 38 (10) 1991-1995
  • 61 Self WH, Wunderink RG, Williams DJ. et al. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomes. Clin Infect Dis 2016; 63 (03) 300-309
  • 62 Aliberti S, Reyes LF, Faverio P. et al; GLIMP investigators. Global initiative for methicillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study. Lancet Infect Dis 2016; 16 (12) 1364-1376
  • 63 Curtis CE, Al Bahar F, Marriott JF. The effectiveness of computerised decision support on antibiotic use in hospitals: a systematic review. PLoS One 2017; 12 (08) e0183062