Prevalence and Outcomes of Previously Healthy Adults Among Patients Hospitalized With Community-Onset Sepsis

Abstract

Background

Devastating cases of sepsis in previously healthy patients have received widespread attention and have helped to catalyze state and national mandates to improve sepsis detection and care. However, it is unclear what proportion of patients hospitalized with sepsis previously were healthy and how their outcomes compare with those of patients with comorbidities.

Research Question

Among adults hospitalized with community-onset sepsis, how many previously were healthy and how do their outcomes compare with those of patients with comorbidities?

Study Design and Methods

We retrospectively identified all adults with community-onset sepsis hospitalized in 373 US hospitals from 2009 through 2015 using clinical indicators of presumed infection and organ dysfunction (Centers for Disease Control and Prevention’s Adult Sepsis Event criteria). Comorbidities were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied generalized linear mixed models to measure the associations between the presence or absence of comorbidities and short-term mortality (in-hospital death or discharge to hospice), adjusting for severity of illness on admission.

Results

Of 6,715,286 hospitalized patients, 337,983 (5.0%) were hospitalized with community-onset sepsis. Most patients with sepsis (329,052 [97.4%]) had received a diagnosis of at least one comorbidity; only 2.6% previously were healthy. Patients with sepsis who previously were healthy were younger than those with comorbidities (mean age, 58.0 ± 19.8 years vs 67.0 ± 16.5 years), were less likely to require ICU care on admission (37.9% vs 50.5%), and were more likely to be discharged home (57.9% vs 45.6%), rather than to subacute facilities (16.3% vs 30.8%), but showed higher short-term mortality rates (22.8% vs 20.8%; P < .001 for all). The association between previously healthy status and higher short-term mortality persisted after risk adjustment (adjusted OR, 1.99; 95% CI, 1.87-2.13).

Interpretation

The vast majority of patients hospitalized with community-onset sepsis harbor pre-existing comorbidities. However, previously healthy patients may be more likely to die when they seek treatment at the hospital with sepsis compared with patients with comorbidities. These findings underscore the importance of early sepsis recognition and treatment for all patients.

FOR EDITORIAL COMMENT, SEE PAGE 14

Take-home Points.

Study Question: What proportion of patients hospitalized for sepsis previously were healthy and how do their outcomes compare with those of patients with comorbidities?

Results: In this cohort study of 6.7 million patients admitted to 373 US hospitals, only 2.6% of patients with sepsis were healthy previously, compared with 6.2% of those hospitalized without sepsis. Short-term mortality rates were higher in previously healthy patients vs those with comorbidities (22.8% vs 20.8%), a finding that persisted after risk adjustment.

Interpretation: The vast majority of patients with sepsis have comorbidities, but previously healthy patients may be at higher risk of death when sepsis does develop.

Sepsis is a leading cause of death, disability, and cost.^1,2 Despite its high burden, awareness of sepsis among the general public, lay media, and policymakers traditionally has been low.^3,4 However, over the last decade, devastating cases of sepsis in previously healthy people, including children, young adults, and celebrities, have received widespread attention and, along with efforts of federal agencies and professional societies, have helped to catalyze state and national mandates to improve sepsis detection and care.^{5, 6, 7}

Notwithstanding these high-profile cases of sepsis in previously healthy people, it is unclear what fraction of adults hospitalized with sepsis fit this profile. A better understanding of the prevalence of previously healthy status among patients hospitalized with sepsis and how their outcomes compare with those of patients with comorbidities may help to improve sepsis recognition, quality of care, and prognostication in an important population and may provide context for high-profile reports of sepsis-associated deaths in previously healthy patients. We sought to address these questions using objective clinical criteria to identify patients with community-onset sepsis and a comprehensive administrative definition to identify comorbid conditions.

Study Design and Methods

Design, Data Sources, and Population

This was a retrospective cohort study of adults 20 years of age or older admitted to 373 US hospitals between January 2009 and September 2015 (corresponding to the end of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code use era). Data were drawn from three nonoverlapping datasets: Cerner HealthFacts, HCA Healthcare, and Institute for Health Metrics. These datasets are collectively representative of US hospitals in size, teaching status, and geographical distribution.⁸ The study was approved with a waiver of informed consent by the institutional review board at Harvard Pilgrim Health Care Institute.

Sepsis Definition

Prior epidemiologic studies primarily have used administrative data to define sepsis, but these are limited by low sensitivity, inconsistent definitions, and variable diagnosis and coding practices that are changing over time.^{9, 10, 11, 12, 13} We therefore identified sepsis hospitalizations using Centers for Disease Control and Prevention Adult Sepsis Event surveillance criteria,⁸ which require concurrent clinical indicators of presumed serious infection (blood culture order and ≥ 4 consecutive days of antibiotic use, or fewer if the patient died, was discharged to hospice, or transferred to another acute hospital before 4 days) and acute organ dysfunction (initiation of vasopressors or mechanical ventilation; elevated lactate; or changes in baseline creatinine or glomerular filtration rate, bilirubin, or platelet count). This validated definition previously was shown to have comparable sensitivity and higher specificity than implicit administrative definitions (ie, concurrent infection and organ dysfunction codes) and comparable specificity with higher sensitivity than explicit sepsis diagnosis codes relative to Sepsis-3 criteria as determined by medical record reviews.⁸ We focused on patients with community-onset sepsis, defined by blood culture samples drawn and first antibiotic administered on hospital day 1 or 2.¹⁴

Definitions of Comorbidities

Although the Charlson¹⁵ and Elixhauser¹⁶ comorbidity index scores commonly are used to define comorbidities, both methods are optimized for mortality prediction, rather than accurate epidemiologic descriptions. Indeed, many important chronic comorbidities are not included in either scale, including cystic fibrosis, congenital immunodeficiencies, and leukemia. In addition, some diagnoses, such as fluid and electrolyte disorders, may better reflect acute rather than chronic conditions. To develop a comprehensive set of diagnoses indicative of chronic medical comorbidities, two clinicians (M. A. and C. R.) independently reviewed all ICD-9-CM codes in the Agency for Healthcare Research and Quality Clinical Classifications Software.¹⁷ Comorbidities were classified as major (eg, heart failure, malignancy) or minor (eg, hypertension, benign neoplasm) based on their likely impact on patients’ short-term mortality (e-Table 1). Pregnancy with no other comorbidities was considered a separate category, given its temporary nature and the relatively higher risk of sepsis during this period.¹⁸ Cohen’s value for agreement between evaluators on defining chronic comorbidities was 0.975, indicating a high level of agreement. Disagreements were resolved by a third clinician (M. K). Previously healthy patients were defined as those without any chronic comorbidity codes.

Statistical Analysis

Descriptive statistics were used to summarize continuous variables using means and SDs and categorical variables using frequencies and percentages. Between-group comparisons were performed using the t test and χ ² test for continuous and categorical variables, respectively. A generalized linear mixed model analysis was used to fit a logistic regression model to determine the association between comorbid status (as a binary variable) and short-term mortality (defined as in-hospital death or discharge to hospice), adjusting for age, sex, race, infection site (as determined by ICD-9-CM codes),¹⁹ and severity of illness on admission (need for ICU admission, vasopressors, mechanical ventilation, creatinine, bilirubin, platelet count, WBC count, hematocrit, anion gap, aspartate transaminase, and albumin). Missing data for laboratory values were assumed to be normal, as is commonly done for severity of illness scores. Individual hospitals were treated as random effects. Model results from the three data sources were compiled using study-level meta-analysis.²⁰

We conducted sensitivity analyses using two alternate definitions of previously healthy: (1) a broader definition that included patients without major comorbidities, but did include those with minor comorbidities, pregnancy, or no comorbidities and (2) a narrower definition that included only relatively young patients (< 60 years of age) without any major comorbidities. All statistical analyses were conducted in R version 3.6.1 software (R Foundation for Statistical Computing), and P < .05 (two-sided) was considered statistically significant.

Results

The cohort included 6,715,286 adult hospitalizations, most of which occurred in the Southern United States (52.8%), in medium-sized hospitals (58.2%), and in nonteaching facilities (51.5%). Among these 6.7 million hospitalizations, 337,983 patients (5.0%) had community-onset sepsis. Most patients with sepsis had at least one comorbidity (96.1% had a major comorbidity, 1.2% had a minor comorbidity alone, and 0.1% were pregnant only); only 8,931 patients (2.6%) previously were healthy. By comparison, 6.2% of hospitalized patients without sepsis were healthy previously (P < .001) (Fig 1). Hospitalized patients without sepsis also showed fewer major comorbidities compared with patients with sepsis (Fig 1). Among patients with sepsis, the most common comorbidities were hypertension without complications, anemia, and diabetes (Fig 2). Previously healthy patients with sepsis were younger (mean age, 58 years vs 67 years) than patients with sepsis and comorbidities. Notably, half of previously healthy patients with sepsis (50.6%) were younger than 60 years compared with less than one-third of patients (31.0%) for the same age group among the patients with sepsis and comorbidities.

Figure 1.

Bar graph showing prevalence of comorbidities in hospitalized patients with and without community-onset sepsis.

Figure 2.

Graph showing the adjusted risk for short-term mortality and prevalence of different comorbidities among patients with community-onset sepsis. ORs are adjusted for demographics, severity of illness on admission, and type of infection. Prevalence percentages do not sum to 100% because patients can have multiple comorbidities.

Compared with patients with sepsis with comorbidities, previously healthy patients with sepsis required vasopressors on admission more often (28.9% vs 26.8%), but less mechanical ventilation (12.6% vs 24.1%) and ICU care (37.9% vs 50.5%; P < .001 for all comparisons) (Table 1). Previously healthy patients with sepsis were less likely to have coding for a specific site of infection, such as pneumonia or a urinary tract infection, but showed similar distributions of pathogens identified on blood culture examinations compared with patients with comorbidities (Table 2). Previously healthy patients showed higher short-term mortality rates (22.8% vs 20.8%), but were more likely to be discharged home (57.9% vs 45.6) vs to subacute facilities (16.3% vs 30.8%; P < .001 for all comparisons).

Table 1.

Characteristics of Patients With Community-Onset Sepsis: Comorbid Conditions vs Previously Healthy Groups (N = 337,983)

Characteristic	Comorbidity Conditions Group (n = 329,052 [97.4%])	Previously Healthy Group (n = 8,931 [2.6%])	P Value
Charlson comorbidity index	2.3 ± 2.1	0 ± 0.4	< .001
Elixhauser comorbidity index	10.4 ± 8.9	1.4 ± 2.6	< .001
Age, y	67.0 ± 16.5	58.0 ± 19.8	< .001
Age category, y			< .001
20-40	22,419 (91.7)	2,031 (8.3)
40-60	79,733 (97.0)	2,491 (3.0)
60-80	140,794 (98.1)	2,723 (1.9)
> 80	86,106 (98.1)	1,686 (1.9)
Male sex	159,603 (48.5)	4,419 (49.5)	.07
Race			< .001
White	232,034 (71.4)	5,961 (68)
Asian	8,538 (2.6)	210 (2.4)
Black	45,367 (14)	1,301 (14.8)
Hispanic	28,903 (8.9)	865 (9.9)
Other	10,129 (3.1)	431 (4.9)
ICU admission	166,307 (50.5)	3,389 (37.9)	< .001
ICU LOS, d	6.3 ± 11.7	6.4 ± 27.6	.83
Hospital LOS, d	10.7 ± 10.4	9.5 ± 11.4	< .001
CDC organ dysfunction
Ventilation	79,219 (24.1)	1,123 (12.6)	< .001
Vasopressors	88,338 (26.8)	2,580 (28.9)	< .001
Lactate	152,834 (46.4)	3,843 (43)	< .001
Creatinine	161,199 (49)	3,957 (44.3)	< .001
Bilirubin	27,360 (8.3)	1,187 (13.3)	< .001
Platelet	33,210 (10.1)	978 (11)	.008
Positive blood culture results	51,839 (15.8)	1,503 (16.8)	.006
Infection diagnosis
Septicemia bacteremia	152,625 (46.4)	2,427 (27.2)	< .001
Pulmonary	159,573 (48.5)	2,088 (23.4)	< .001
Genitourinary	108,275 (32.9)	1,468 (16.4)	< .001
Intraabdominal	44,012 (13.4)	1,124 (12.6)	.03
Skin and soft tissue	34,134 (10.4)	753 (8.4)	< .001
Bone or joint	9,429 (2.9)	122 (1.4)	< .001
Obstetric or gynecologic	1,812 (0.6)	73 (0.8)	< .001
CNS	3,159 (1)	102 (1.1)	.082
Other	59,613 (18.1)	879 (9.8)	< .001
Disposition			< .001
Death	47,565 (14.5)	1,773 (19.9)
Hospice	20,878 (6.3)	256 (2.9)
Hospital transfer	9,184 (2.8)	278 (3.1)
Subacute facility	10,1347 (30.8)	1,454 (16.3)
Home	150,078 (45.6)	5,170 (57.9)

Data are presented as No. (%) or mean ± SD. CDC = Centers for Disease Control and Prevention; LOS = length of stay.

Table 2.

Positive Blood Culture Pathogen Findings for Patients With Community-Onset Sepsis by Comorbid Conditions vs Previously Healthy Status

Variable	Comorbid Conditions Group (N = 51,839)	Previously Healthy Group (n = 1,503)	P Value
Pathogena
Escherichia	12,804 (24.7)	396 (26.3)	.144
Streptococcus	10,367 (20)	354 (23.6)	< .001
Staphylococcus aureus	10,617 (20.5)	276 (18.4)	.045
Klebsiella	4,843 (9.3)	166 (11)	.026
Enterococcus	4,035 (7.8)	110 (7.3)	.507
Yeast	2,602 (5)	69 (4.6)	.453
Proteus	2,008 (3.9)	60 (4)	.815
Pseudomonas	2,259 (4.4)	53 (3.5)	.119
Enterobacter	1,360 (2.6)	36 (2.4)	.585
Bacteroides	1,039 (2)	32 (2.1)	.734
Pathogen type
Gram-negative	25,647 (49.5)	765 (50.9)	.276
Gram-positive	24,499 (47.3)	706 (47)	.826
Anaerobe	2,874 (5.5)	86 (5.7)	.767
Fungus	2,799 (5.4)	70 (4.7)	.209
Polymicrobial	3,688 (7.1)	110 (7.3)	.276

Data are presented as No. (%), unless otherwise indicated.

^aPatient can have multiple pathogens; pathogens are sorted by decreasing prevalence in the previously healthy group.

After controlling for baseline characteristics and severity of illness on admission, the association between previously healthy status and short-term death persisted (adjusted OR, 1.99; 95% CI, 1.87-2.13) (Table 3). Among patients with sepsis with comorbidities, failure to thrive, solid cancer, stem cell transplantation, chronic liver disease, hematologic malignancy, and dementia were associated most strongly with increased mortality (Fig 2). The association between previously healthy status and mortality in patients with sepsis was consistent across all three datasets (e-Table 2).

Table 3.

Risk-Adjusted Multivariate Model Results for Short-Term Mortality in Patients With Community-Onset Sepsis (N = 337,983)

Variable	OR (95% CI)	P Value
Previously healthy	1.99 (1.87-2.13)	< .001
Demographics
Age	1.04 (1.04-1.04)	< .001
Male sex	1.01 (0.99-1.02)	.599
Race
White	Reference	—
Asian	0.9 (0.84-0.96)	.002
Black	0.95 (0.92-0.98)	.001
Hispanic	1.03 (0.99-1.08)	.153
Other	0.92 (0.87-0.97)	.003
Severity of illness on admissiona
ICU admission	1.35 (1.32-1.39)	< .001
CDC organ dysfunction—ventilation	2.33 (2.27-2.38)	< .001
CDC organ dysfunction—vasopressors	2.27 (2.22-2.32)	< .001
Peak creatinine, mg/dL	1.01 (1.01-1.01)	< .001
Peak bilirubin, mg/dL	1.09 (1.09-1.09)	< .001
Minimum platelet, × 109/L	1.000 (1.000-1.000)	< .001
Peak WBC, × 109/L	1.01 (1.01-1.01)	< .001
Peak AST, units/L	1.000 (1.000-1.000)	< .001
Minimum hematocrit, %	1.002 (1.001-1.003)	.002
Peak anion gap, mEq/L	1.03 (1.03-1.03)	< .001
Minimum albumin, mg/dL	0.54 (0.53-0.54)	< .001
Port or type of infection
Septicemia bacteremia	1.34 (1.32-1.37)	< .001
Pulmonary	1.11 (1.09-1.14)	< .001
Genitourinary	0.7 (0.68-0.72)	< .001
Intraabdominal	0.67 (0.65-0.69)	< .001
Skin and soft tissue	0.66 (0.63-0.68)	< .001
Bone or joint	0.61 (0.57-0.66)	< .001
Obstetric or gynecologic	0.56 (0.46-0.67)	< .001
CNS	1.19 (1.07-1.31)	.001
Other	0.68 (0.66-0.7)	< .001

The numbers in the table reflect model results compiled from all three data sources. AST = aspartate aminotransferase; CDC = Centers for Disease Control and Prevention.

^aMissing laboratory values were imputed with normal values.

When defining previously healthy as having no major comorbidities (ie, only pregnancy, minor comorbidities, or no comorbidities), the prevalence among patients with sepsis was 3.9%, and short-term mortality was 18.3% vs 21.0% for those with major comorbidities. When defining previously healthy as age younger than 60 years, no comorbidities, and not pregnant, the prevalence among patients with sepsis was 1.3% and short-term mortality was 14.6%% vs 20.9% for those 60 years of age or older or those with comorbidities. However, after adjusting for age, sex, race, infection site, and severity of illness, the previously healthy group using both of these definitions still had a higher risk for short-term mortality (adjusted ORs, 1.32 [95% CI, 1.25-1.40] and 2.01 [95% CI, 1.82-2.22], respectively).

Discussion

High-profile reports of sepsis in previously healthy patients have increased sepsis awareness and have helped to catalyze sepsis reporting and management mandates. Despite these high-profile reports, our study suggested that previously healthy patients account for less than 3% of patients hospitalized with sepsis. However, these patients may be more likely to die when they seek treatment at the hospital with sepsis compared with those with comorbid conditions. The risk-adjusted association between previously healthy status and higher mortality when hospitalized with sepsis was similar when expanding the definition of previously healthy to include comorbidities expected to have a relatively low debilitating effect on functional status and when narrowing the definition to focus on relatively younger adults without any comorbidities.

The prevalence of comorbid conditions among hospitalized patients with sepsis was substantially higher compared with hospitalized patients without sepsis. The high prevalence of comorbid conditions among patients with sepsis is consistent with prior work demonstrating that many comorbidities are risk factors for development of sepsis and subsequent death.^{21, 22, 23} Several serious comorbidities, particularly oncologic diagnoses, dementia, and chronic liver disease, were associated with a very high risk of sepsis-associated mortality, consistent with prior studies.^{24, 25, 26} This underscores the importance of preventative care and health maintenance to reduce the risk of acquiring and dying of sepsis.²⁷ Notably, several comorbidities, such as diabetes, benign neoplasms, immunodeficiency disorders, and anemia, actually were associated with a lower risk of mortality. This likely reflects the fact that these analyses were relative comparisons among patients hospitalized with sepsis, rather than a general outpatient healthy cohort. As such, if the average patient with sepsis has multiple severe comorbidities, some conditions may be associated with lower mortality, even if they are not inherently protective. Similarly, our findings should not be interpreted to imply that healthy individuals are more likely overall to experience or die of sepsis, because we did not assess sepsis incidence rates in the general population, but rather focused on patients hospitalized with sepsis alone.

Our observation that short-term mortality rates were higher in previously healthy patients vs patients with comorbidities in whom sepsis does develop and who seek treatment at the hospital is novel and counterintuitive. One potential explanation is that previously healthy patients may wait longer to seek hospital treatment, and therefore are more severely ill on presentation. In contrast, patients with comorbidities may be followed up more closely by their health care providers and may be quicker to seek treatment at the hospital for symptoms of sepsis. This is supported by the slightly higher rates of vasopressor use on admission in the previously healthy group, because shock is the most severe manifestation of sepsis. The relative resilience of these patients also may mean that a higher burden of infection is present by the time they demonstrate symptoms severe enough to necessitate hospitalization. Some healthy patients who are unfortunate enough to acquire a life-threatening infection also may produce an overzealous immune response leading to greater organ dysfunction and risk of death. Interestingly, however, aside from the higher rate of vasopressor use, the previously healthy group showed overall lower rates of organ dysfunction on admission. The observation that the previously healthy group showed less organ dysfunction at presentation, along with our analysis demonstrating persistently higher mortality rates even after adjusting for severity of illness on admission, raises the possibility that worse outcomes may be mediated by differences in how these patients are treated. In particular, sepsis diagnosis and treatment may be delayed in previously healthy patients if clinicians presume younger and healthier patients are less likely to have sepsis or if clinicians presume these patients have a better prognosis. The lower rates of ICU admission indirectly support this possibility. Delays and worse outcomes also may occur if healthy patients more often have unusual infections or infections without a clear source, a possibility supported by the lower rate of specific infectious diagnoses observed in this group. Notably, however, healthy patients with sepsis showed similar types and distributions of bloodstream pathogens compared with patients with comorbidities. Another possibility is that less severe illnesses may be treated inappropriately as sepsis more often when comorbid conditions are present because of the difficulty differentiating whether acute organ dysfunctions are the result of infection vs noninfectious exacerbations of pre-existing comorbidities. Furthermore, known genetic variability exists in the predisposition to infection and sepsis²⁸; it is possible that genetically predisposed patients may seek treatment earlier in life and also may be more likely to die of these infections.

Our finding that less than 3% of sepsis hospitalizations occurred in previously healthy adults must be taken in the context of the high overall national incidence of sepsis. The Centers for Disease Control and Prevention, for example, estimates that sepsis afflicts 1.7 million adults annually in the United States.²⁹ This then translates into sepsis potentially affecting > 40,000 previously healthy adults and contributing to 10,000 deaths each year. These figures underscore the total burden of sepsis among healthy adults, particularly given prior work showing that even previously healthy patients who survive a sepsis hospitalization go on to have worse long-term outcomes compared with patients with nonseptic critical illness and the general population.³⁰

Our study has several limitations. First, our data source did not allow us to examine sepsis incidence and impact among the full nonhospitalized population of healthy patients and patients with chronic illnesses. However, our goal was to understand better, among patients hospitalized for sepsis, how many have no comorbid conditions and how their outcomes compare with those of patients hospitalized with sepsis who do have comorbid conditions. Second, no gold standard definition for comorbidity exists in the context of descriptive epidemiology. However, we assessed all potential ICD-9-CM codes to develop a comprehensive definition explicitly for this purpose. Third, the distinction between previously healthy patients and patients with comorbidities is somewhat arbitrary, because many patients with chronic comorbidities nonetheless can be highly functional and have life expectancies that mirror healthy patients. Fourth, we did not have prehospitalization diagnosis codes from outpatient encounters or prior hospitalizations to augment our comorbidity identification strategy; hence, some patients with comorbidities may have been miscoded as being previously healthy. Similarly, without medical record reviews, we cannot rule out the possibility that physicians and hospitals may have coded preferentially for acute rather than chronic conditions in some patients with severe illness with sepsis.^31,32 Conversely, coding errors could have led to overestimation of the prevalence of some comorbidities, particularly if some hospitals miscoded some acute organ dysfunctions as chronic conditions. Fifth, the Adult Sepsis Event definition relies on blood culture orders and antibiotics to identify patients with sepsis, and it is possible that clinicians’ thresholds to perform these actions as well as to admit patients to the hospital may be different in patients who are healthy vs comorbid at baseline. This could introduce selection bias into our analysis. However, these limitations likely would apply to other sepsis surveillance methods as well. Sixth, as described above, we have only limited insight into the mechanisms underlying the higher mortality rates in previously healthy patients with sepsis. This is an important topic for future research. Seventh, our data were limited to adult patients, and so we have no insight into the extent to which our findings apply to children. This is a particularly important area for additional research given the high burden of sepsis among children and their generally greater health and resilience compared with adults.³³ Finally, our study was conducted using data that preceded the COVID-19 pandemic. It will be important in the future to update our analyses with pandemic data given that many young and healthy patients have been hospitalized and died of severe COVID-19, and the growing consensus that SARS-CoV-2 is a valid and important cause of sepsis.³⁴

Interpretation

This large cohort study using detailed clinical data from 373 US hospitals demonstrated that the vast majority of patients hospitalized with community-onset sepsis have pre-existing comorbidities. However, previously healthy patients may be at higher risk of death when sepsis does develop. These findings underscore the importance of preventative care and health maintenance to prevent sepsis hospitalizations, provide context for high-profile reports about sepsis deaths in previously healthy people, and underscore the importance of early sepsis recognition and treatment for all patients.