Subscribe to RSS
DOI: 10.1055/s-0041-1741013
Life-Threatening Infections: Pulmonary and Systemic Infections





Infections are among the most common indications for hospitalization around the world to include admission to an intensive care unit (ICU) for life-threatening infections (LTIs). Increasingly the management of LTIs has become more complex due to the emergence of new infections not previously recognized, escalating antimicrobial resistance among pathogens causing LTIs, and host changes increasing the predisposition to and worsening the outcomes of LTIs due to either increasing immunosuppression or the application of artificial devices such as tunneled intravascular catheters, ventricular assist devices, and intracranial monitoring devices. The emergence of novel LTIs is of particular importance as difficulties in establishing the diagnosis of such infections and the lack of available therapies hinder effective treatment of these infections. Candida auris, Middle Eastern respiratory syndrome coronavirus, novel coronavirus (COVID-19, Wuhan, China), pan-resistant Escherichia coli, and Zika virus are recent examples of such infections that have resulted in significant morbidity and mortality.[1] [2] [3] [4] [5] [6] COVID-19 is a novel respiratory virus infection that already is estimated to have accounted for 7 million deaths globally.[7] Moreover, the recent COVID-19 pandemic has resulted in significant economic distress with the global economy contracting by 3.5% in 2020.[8]
Escalating resistance of pathogens to available antimicrobial agents is also of paramount importance, as the outcome of LTIs is generally most influenced by the timing of an appropriate antimicrobial regimen (i.e., an antimicrobial regimen that has activity against the causative pathogens based on in vitro susceptibility assessment). The administration of an inappropriate antimicrobial regimen can be associated with more than a doubling of the mortality risk especially for LTIs such as septic shock.[9] [10] [11] [12] [13] The Extended Study on Prevalence of Infection in Intensive Care III study found that among the 15,165 qualifying patients, 8,135 (54%) had at least one suspected or proven infection on the study day.[14] Interestingly, multilevel analysis demonstrated that infection with antibiotic-resistant pathogens including vancomycin-resistant Enterococcus, Klebsiella species resistant to β-lactam antibiotics, or carbapenem-resistant Acinetobacter species were associated with a higher risk of in-hospital death compared with infection with other microorganisms.[14] The concern over escalating antimicrobial resistance is present for all types of infections (bacterial, fungal, viral). The World Health Organization considers antimicrobial resistance to be a major threat to human health and a recent Wellcome Trust report suggests that nearly 300 million individuals will die over the next several decades as a direct result of antimicrobial resistance.[15] [16] Similarly, in the United States, antibiotic-resistant pathogens cause more than 2 million infections and 23,000 deaths per year as reported by the Centers for Disease Control and Prevention.[17] The IDSA launched a “10 by 20” initiative in 2010 to have at least 10 original antibiotics developed and approved for use by 2020.[18] Although this initiative succeeded, the IDSA working committee recently noted that antibiotic drug development might have peaked during the last decade for years to come and that without continued advances, the historical problem of antibiotic resistance is likely to intensify leading to future drug inadequacies.[19]
In this issue of Seminars in Respiratory and Critical Care Medicine, we have brought together an international group of authors to discuss the problem of LTIs. The goal of this seminar is to provide a succinct series of articles not only reviewing the most important LTIs as described by the World Health Organization ([Table 1]) but also describing updates in terms of their diagnosis and treatment.[20] As recent experience has shown, LTIs will continue to evolve over time posing serious threats to health and the global economy. Therefore, as a medical community we must maintain a state of preparedness to deal with current LTIs as well as novel threats in the future.
Publication History
Article published online:
16 February 2022
© 2022. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Eyre DW, Sheppard AE, Madder H. et al. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med 2018; 379 (14) 1322-1331
- 2 Spivak ES, Hanson KE. Candida auris: an emerging fungal pathogen. J Clin Microbiol 2018; 56 (02) e01588-e17
- 3 Li Q, Guan X, Wu P. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020; 382 (13) 1199-1207
- 4 McGann P, Snesrud E, Maybank R. et al. Escherichia coli harboring mcr-1 and blaCTX-M on a novel IncF plasmid: first report of mcr-1 in the United States. Antimicrob Agents Chemother 2016; 60 (07) 4420-4421
- 5 Arabi YM, Balkhy HH, Hayden FG. et al. Middle East respiratory syndrome. N Engl J Med 2017; 376 (06) 584-594
- 6 Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med 2016; 374 (16) 1552-1563
- 7 IHME – Measuring what matters. Accessed August 2, 2021 at: http://www.healthdata.org/news-release/covid-19-has-caused-69-million-deaths-globally-more-double-what-official-reports-show
- 8 Yeyati EL, Filipinni F. Social and economic impact of COVID-19. Accessed August 2, 2021 at: https://www.brookings.edu/wp-content/uploads/2021/06/Social-and-economic-impact-COVID.pdf
- 9 Kumar A, Ellis P, Arabi Y. et al; Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009; 136 (05) 1237-1248
- 10 Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999; 115 (02) 462-474
- 11 Zasowski EJ, Bassetti M, Blasi F. et al. A systematic review of the effect of delayed appropriate antibiotic treatment on the outcomes of patients with severe bacterial infections. Chest 2020; 158 (03) 929-938
- 12 Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54 (12) 1739-1746
- 13 Kadri SS, Lai YL, Warner S. et al; Forming the National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH-ARORI). Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals. Lancet Infect Dis 2021; 21 (02) 241-251
- 14 Vincent JL, Sakr Y, Singer M. et al; EPIC III Investigators. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020; 323 (15) 1478-1487
- 15 World Health Organization. 2020 Report on Antimicrobial Resistance. Accessed July 26, 2021 at: https://www.who.int/antimicrobial-resistance/interagency-coordination-group/final-report/en/
- 16 Wellcome Trust, United Kingdom Department of Health. 2014 Review on Antimicrobial Resistance. Accessed September 26, 2021 at: https://amr-review.org/
- 17 Centers for Disease Control and prevention. Antibiotic Resistance: A Global Threat. Accessed July 26, 2021 at: https://www.cdc.gov/drugresistance/solutions-initiative/stories/ar-global-threat.html
- 18 Infectious Diseases Society of America. The 10 × '20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 2020; 50: 1081-1083
- 19 Talbot GH, Jezek A, Murray BE. et al; Infectious Diseases Society of America. The Infectious Diseases Society of America's 10 × '20 Initiative (10 New Systemic Antibacterial Agents US Food and Drug Administration Approved by 2020): Is 20 × '20 a Possibility?. Clin Infect Dis 2019; 69 (01) 1-11
- 20 Bloom DE, Cadarette D. Infectious disease threats in the twenty-first century: strengthening the global response. Front Immunol 2019; 10: 549