Incidence, trends, and outcomes of infection sites among hospitalizations of sepsis: A nationwide study

Autoři: Eric H. Chou aff001;  Shaynna Mann aff001;  Tzu-Chun Hsu aff003;  Wan-Ting Hsu aff004;  Carolyn Chia-Yu Liu aff005;  Toral Bhakta aff002;  Dahlia M. Hassani aff002;  Chien-Chang Lee aff003
Působiště autorů: Department of Emergency Medicine, John Peter Smith Hospital, Fort Worth, Texas, United States of America aff001;  Department of Emergency Medicine, Baylor Scott and White All Saints Medical Center, Fort Worth, Texas, United States of America aff002;  Department of Emergency Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan aff003;  Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America aff004;  McTimoney College of Chiropractic, School of Health, BPP University, Abingdon, Oxfordshire, United Kingdom aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article



To determine the trends of infection sites and outcome of sepsis using a national population-based database.

Materials and methods

Using the Nationwide Inpatient Sample database of the US, adult sepsis hospitalizations and infection sites were identified using a validated approach that selects admissions with explicit ICD-9-CM codes for sepsis and diagnosis/procedure codes for acute organ dysfunctions. The primary outcome was the trend of incidence and in-hospital mortality of specific infection sites in sepsis patients. The secondary outcome was the impact of specific infection sites on in-hospital mortality.


During the 9-year period, we identified 7,860,687 admissions of adult sepsis. Genitourinary tract infection (36.7%), lower respiratory tract infection (36.6%), and systemic fungal infection (9.2%) were the leading three sites of infection in patients with sepsis. Intra-abdominal infection (30.7%), lower respiratory tract infection (27.7%), and biliary tract infection (25.5%) were associated with highest mortality rate. The incidences of all sites of infections were trending upward. Musculoskeletal infection (annual increase: 34.2%) and skin and skin structure infection (annual increase: 23.0%) had the steepest increase. Mortality from all sites of infection has decreased significantly (trend p<0.001). Skin and skin structure infection had the fastest declining rate (annual decrease: 5.5%) followed by primary bacteremia (annual decrease: 5.3%) and catheter related bloodstream infection (annual decrease: 4.8%).


The anatomic site of infection does have a differential impact on the mortality of septic patients. Intra-abdominal infection, lower respiratory tract infection, and biliary tract infection are associated with higher mortality in septic patients.

Klíčová slova:

Bacteremia – Bloodstream infections – Death rates – Fungal diseases – Genitourinary infections – Lower respiratory tract infections – Sepsis – Skin infections


1. Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med 2012; 40: 754–761. doi: 10.1097/CCM.0b013e318232db65 21963582

2. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med 2013; 41: 1167–1174. doi: 10.1097/CCM.0b013e31827c09f8 23442987

3. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000–2007). Chest 2011; 140: 1223–1231. doi: 10.1378/chest.11-0352 21852297

4. Torio CM, Andrews RM. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011: Statistical Brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006.

5. Vincent JL, Opal SM, Marshall JC, Tracey KJ. Sepsis definitions: time for change. Lancet (London, England) 2013; 381: 774–775.

6. Huggan PJ, Bell A, Waetford J, Obertova Z, Lawrenson R. Evidence of High Mortality and Increasing Burden of Sepsis in a Regional Sample of the New Zealand Population. Open forum infectious diseases 2017; 4: ofx106. doi: 10.1093/ofid/ofx106 28948175

7. 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 2016; 315: 801–810. doi: 10.1001/jama.2016.0287 26903338

8. Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence 2014; 5: 36–44. doi: 10.4161/viru.25436 23774844

9. Zahar JR, Timsit JF, Garrouste-Orgeas M, Francais A, Vesin A, Descorps-Declere A et al. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Crit Care Med 2011; 39: 1886–1895. doi: 10.1097/CCM.0b013e31821b827c 21516036

10. Jeganathan N, Yau S, Ahuja N, Otu D, Stein B, Fogg L et al. The characteristics and impact of source of infection on sepsis-related ICU outcomes. J Crit Care 2017; 41: 170–176. doi: 10.1016/j.jcrc.2017.05.019 28564621

11. Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A, Kumar A. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med 2014; 189: 1204–1213. doi: 10.1164/rccm.201310-1875OC 24635548

12. Motzkus CA, Luckmann R. Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis. J Intensive Care Med 2017; 32: 473–479. doi: 10.1177/0885066615627778 26880006

13. Whitney CG, Harper SA. Lower respiratory tract infections: prevention using vaccines. Infect Dis Clin North Am 2004; 18: 899–917. doi: 10.1016/j.idc.2004.07.008 15555831

14. Baldo V, Cocchio S, Gallo T, Furlan P, Romor P, Bertoncello C et al. Pneumococcal Conjugated Vaccine Reduces the High Mortality for Community-Acquired Pneumonia in the Elderly: an Italian Regional Experience. PloS One 2016; 11: e0166637. doi: 10.1371/journal.pone.0166637 27846277

15. Overview of the National Inpatient Sample (NIS). 2015. Available from:

16. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348: 1546–1554. doi: 10.1056/NEJMoa022139 12700374

17. Rhee C, Dantes R, Epstein L, Murphy DJ, Seymour CW, Iwashyna TJ et al. Incidence and Trends of Sepsis in US Hospitals Using Clinical vs Claims Data, 2009–2014. JAMA 2017; 318: 1241–1249. doi: 10.1001/jama.2017.13836 28903154

18. Zhang J, Yu KF. What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 1998; 280: 1690–1691. doi: 10.1001/jama.280.19.1690 9832001

19. Lee CC, Yo CH, Lee MG, Tsai KC, Lee SH, Chen YS et al. Adult sepsis—A nationwide study of trends and outcomes in a population of 23 million people. Journal Infect 2017; 75: 409–419.

20. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Eng J Med 2001; 345: 1368–1377.

21. [The effect of early goal-directed therapy on treatment of critical patients with severe sepsis/septic shock: a multi-center, prospective, randomized, controlled study]. Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue 2010; 22: 331–334.

22. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S 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: 1589–1596. doi: 10.1097/01.CCM.0000217961.75225.E9 16625125

23. Luna CM, Pulido L, Burgos D. Why is the rate of pneumococcal pneumonia declining? Curr Opin Pulm Med 2018; 24: 205–211. doi: 10.1097/MCP.0000000000000478 29538078

24. Brook I. Microbiology and management of abdominal infections. Dig Dis Sci 2008; 53: 2585–2591. doi: 10.1007/s10620-007-0194-6 18288616

25. Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet (London, England) 2004; 364: 545–548.

26. Krishna S, Miller LS. Host-pathogen interactions between the skin and Staphylococcus aureus. Curr Opin Microbiol 2012; 15: 28–35. doi: 10.1016/j.mib.2011.11.003 22137885

27. Shapiro NI, Wolfe RE, Moore RB, Smith E, Burdick E, Bates DW. Mortality in Emergency Department Sepsis (MEDS) score: a prospectively derived and validated clinical prediction rule. Crit Care M 2003; 31: 670–675.

28. Chen CC, Chong CF, Liu YL, Chen KC, Wang TL. Risk stratification of severe sepsis patients in the emergency department. Emerg Med J 2006; 23: 281–285. doi: 10.1136/emj.2004.020933 16549574

29. Prucha M, Zazula R, Russwurm S. Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment? Arch Immunol Ther Exp 2017; 65: 37–49.

30. Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, et al. Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 2002; 166: 1197–1205. doi: 10.1164/rccm.200204-302OC 12403688

31. Arnold HM, Micek ST, Skrupky LP, Kollef MH. Antibiotic stewardship in the intensive care unit. Semin Resp Crit Care 2011; 32: 215–227.

32. Goff DA. Antimicrobial stewardship: bridging the gap between quality care and cost. Curr Opin Infect Dis 2011; 24 Suppl 1: S11–20. doi: 10.1097/01.qco.0000393484.17894.05 21200180

33. Whittaker SA, Mikkelsen ME, Gaieski DF, Koshy S, Kean C, Fuchs BD. Severe sepsis cohorts derived from claims-based strategies appear to be biased toward a more severely ill patient population. Crit Care Med 2013; 41: 945–953. doi: 10.1097/CCM.0b013e31827466f1 23385099

34. Iwashyna TJ, Odden A, Rohde J, Bonham C, Kuhn L, Malani P et al. Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis. Med Care 2014; 52: e39–43. doi: 10.1097/MLR.0b013e318268ac86 23001437

35. Jolley RJ, Sawka KJ, Yergens DW, Quan H, Jette N, Doig CJ. Validity of administrative data in recording sepsis: a systematic review. Crit Care 2015; 19: 139. doi: 10.1186/s13054-015-0847-3 25887596

36. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*. Crit Care Med 2014; 42: 625–631. doi: 10.1097/CCM.0000000000000026 24201173

37. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med 2007; 35: 1244–1250. doi: 10.1097/01.CCM.0000261890.41311.E9 17414736

38. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303–1310. doi: 10.1097/00003246-200107000-00002 11445675

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