Clinical Phenotypes of Sepsis in a Cohort of Hospitalized Patients According to Infection Site

Abstract

Objectives: Clinical sepsis phenotypes may be defined by a wide range of characteristics such as site of infection, organ dysfunction patterns, laboratory values, and demographics. There is a paucity of literature regarding the impact of site of infection on the timing and pattern of clinical sepsis markers. This study hypothesizes that important phenotypic variation in clinical markers and outcomes of sepsis exists when stratified by infection site.

Design: Retrospective cohort study.

Setting: Five hospitals within the Wake Forest Health System from June 2019 to December 2019.

Patients: Six thousand seven hundred fifty-three hospitalized adults with a discharge International Classification of Diseases, 10th Revision code for acute infection who met systemic inflammatory response syndrome (SIRS), quick Sepsis-related Organ Failure Assessment (qSOFA), or Sequential Organ Failure Assessment (SOFA) criteria during the index hospitalization.

Interventions: None.

Measurements and main results: The primary outcome of interest was a composite of 30-day mortality or shock. Infection site was determined by a two-reviewer process. Significant demographic, vital sign, and laboratory result differences were seen across all infection sites. For the composite outcome of shock or 30-day mortality, unknown or unspecified infections had the highest proportion (21.34%) and CNS infections had the lowest proportion (8.11%). Respiratory, vascular, and unknown or unspecified infection sites showed a significantly increased adjusted and unadjusted odds of the composite outcome as compared with the other infection sites except CNS. Hospital time prior to SIRS positivity was shortest in unknown or unspecified infections at a median of 0.88 hours (interquartile range [IQR], 0.22-5.05 hr), and hospital time prior to qSOFA and SOFA positivity was shortest in respiratory infections at a median of 54.83 hours (IQR, 9.55-104.67 hr) and 1.88 hours (IQR, 0.47-17.40 hr), respectively.

Conclusions: Phenotypic variation in illness severity and mortality exists when stratified by infection site. There is a significantly higher adjusted and unadjusted odds of the composite outcome of 30-day mortality or shock in respiratory, vascular, and unknown or unspecified infections as compared with other sites.

Keywords: biological variation; phenotypic variability; sepsis; septic shock; systemic inflammatory response syndrome.

Figure 1.

Median hospital time prior to meeting event criteria, by infection site. Error bars represent 95% confidence limits. *p < 0.05 for lower median pairwise difference (reference, respiratory infection). **p < 0.05 for upper median pairwise difference (reference, respiratory infection). ED = emergency department, qSOFA = quick Sepsis-related Organ Failure Assessment, SIRS = systemic inflammatory response syndrome, SOFA = Sequential Organ Failure Assessment.

Figure 2.

Grid heat map of patient characteristics by site of infection. The heat map is based on parameter estimates derived from logistic regression using the pooled dataset. Purple coloration is 2 sds worse than the grand mean for each variable. Orange coloration is 2 sds better than the grand mean for each variable. Darker shading represents greater distance from the mean. Variables are denoted as maximum (max) or minimum (min) indicating that whether highest or lowest value for that variable was used for the analysis. ESR = erythrocyte sedimentation rate, GI = gastrointestinal, GU = genitourinary, SOFA = Sequential Organ Failure Assessment, SSTI = skin and soft tissue infection.

Figure 3.

Adjusted odds ratios for the composite outcome by single infection site (reference, respiratory infection). Odds ratio less than 1 is consistent with lower odds of the outcome of interest as compared with respiratory infection and vice versa for odds ratio greater than 1. Model adjusted for age, sex, body mass index, race, Charlson Comorbidity Index, time to initial antimicrobial receipt, and hospital readmission.