The Impact of Blood Culture Positivity on Community-Acquired Sepsis

Sepsis continues to be a major burden on healthcare, responsible for one in three hospital deaths.¹ Although identifying the organism helps navigate antibiotic prescription, a high prevalence of severely septic patients have negative blood cultures. This Concise Critical Appraisal reviews an article by Ohnuma et al recently published in Critical Care Medicine on the impact of blood culture positivity on community-acquired sepsis, evaluating the epidemiology, resistance profiles, and clinical outcomes of culture-positive and culture-negative sepsis.²

To describe the epidemiology, frequency of blood cultures, patterns of pathogens, and antibiotic treatments initiated in patients presenting with community-acquired sepsis, Ohnuma et al retrospectively reviewed a cohort of patients with community-acquired sepsis. From January 2016 to March 2020, the authors evaluated laboratory and microbiologic data, demographics, admission type (elective vs. nonelective), hospital characteristics, ICD-10 codes, and billing logs. To be included, patients had to have a blood culture drawn within two days of admission, evidence of organ dysfunction within two days of admission, and exposure to a new antibiotic for at least four consecutive days.

Within the nearly four-year period, 147,061 patients from 201 hospitals were included in the study. Of these, 21,167 (14%) had positive blood cultures and 20,326 (14%) had positive cultures from other sites. Blood culture positivity was 25% in patients with septic shock and 18% in patients without shock. Polymicrobial results were present in 7.6% of the cultures. Gram-negative bacilli made up 55%, gram-positive cocci 47%, anaerobes 1.2%, and Candida species 0.7%.

The median age was 67 years, of which 54% were male, 35% were mechanically ventilated, 39% required vasopressors, and length of stay averaged 7 to 8 days. Mortality was 17% in blood culture-positive sepsis, 17% in blood culture-negative sepsis, and 13% in patients with positive cultures from sites other than blood. Common comorbidities for culture-positive sepsis included diabetes (41.1%), renal disease (29%), congestive heart failure (28.4%), chronic obstructive pulmonary disease (22.3%), neurologic disorders (16.5%), liver disease (13.5%), and cancer (11.5%). Admission to the intensive care unit occurred in 75.8% of culture-positive sepsis and 74.3% of culture-negative sepsis.

The most common source of culture-positive sepsis was genitourinary (33.1%), followed by pulmonary (29.9%), skin/soft-tissue (15.4), and intra-abdominal (8.6%). Empiric antibiotic choices included vancomycin (79.4%), cephalosporins (76.3%), penicillins (60.6%), carbapenems (29.6%), and fluoroquinolones (23.3%). The most common combination of antibiotics was vancomycin and piperacillin-tazobactam, which was prescribed in 13% of patients.

The most identified organism was Escherichia coli, followed by Streptococcus, methicillin-sensitive Staphylococcus aureus (MSSA), Klebsiella, and methicillin-resistant S aureus (MRSA). Extended-spectrum beta-lactamases were isolated in 7.3% and carbapenem resistance was isolated in 1.3% of the culture-positive sepsis cases. Mortality was highest in those infected with Acinetobacter (38.6%), followed by Pseudomonas aeruginosa, MSSA, and MRSA. Patients infected with Proteus, Klebsiella, E coli, and Streptococcus had a lower risk of in-hospital mortality.

Ohnuma et al summarized that blood culture-positive sepsis and blood culture-negative sepsis had similar in-hospital mortality, 17.2% and 17.1%, respectively. These findings differ from a prior study that demonstrated a higher mortality in culture-negative severe sepsis.³ A recent meta-analysis of 10 studies found no significant difference in all-cause mortality, need for mechanical ventilation, renal replacement therapy, or intensive care unit length of stay between patients with culture-positive and culture-negative sepsis.⁴ However, this meta-analysis was not limited to community-acquired sepsis. The findings of Afzal et al mirror the 14% blood-culture positivity rate of a prior study of 173,690 patients, with pulmonary and genitourinary infections being the most common.⁵ Unlike prior studies that showed a substantial increase in blood culture-positive patients with septic shock versus sepsis, Cheng et al only found a 7% discrepancy.⁶

The knowledge that, of all organisms, Acinetobacter causes the highest mortality rate can help shape future guidelines and local antibiotic stewardship efforts. The Surviving Sepsis Campaign guidelines recommend that every effort be made to initiate antibiotics within an hour of sepsis recognition and that blood cultures be obtained before antibiotic administration.⁷ Ohnuma et al further illustrates the impact that blood cultures have on clinical outcome. The crucial question of why some community-acquired sepsis patients have positive cultures while others have negative cultures remains unanswered. 

References:

1. Centers for Disease Control and Prevention. What is sepsis? Last reviewed August 24, 2023. Accessed September 11, 2023. https://www.cdc.gov/sepsis/what-is-sepsis.html
2. Ohnuma T, Chihara S, Costin B, et al. Epidemiology, resistance profiles, and outcomes of bloodstream infections in community-onset sepsis in the United States. Crit Care Med. 2023 Sep 1;51(9):1148-1158.
3. Gupta S, Sakhuja A, Kumar G, McGrath E, Nanchal RS, Kashani KB. Culture-negative severe sepsis: nationwide trends and outcomes. Chest. 2016 Dec;150(6):1251-1259.
4. Afzal MS, Chennuri RN, Naveed H, et al. Comparison of clinical outcomes between culture-positive and culture-negative sepsis and septic shock patients: a meta-analysis. Cureus. 2023 Feb 24;15(2):e35416
5. Rhee C, Dantes R, Epstein L, et al; CDC Prevention Epicenter Program. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014. JAMA. 2017 Oct 3;318(13):1241-1249.
6. Cheng MP, Stenstrom R, Paquette K, et al; FABLED Investigators. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis: a diagnostic study. Ann Intern Med. 2019 Oct 15;171(8):547-554.
7. Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247.