Discussion

During the BCx shortage, we observed a relative increase in SEP-1 failures, predominantly driven by late or no BCx obtainment. The proportion of SEP-1 failures due to BCx failures (12.3%) pre-shortage compares similarly to a previous cohort (15.1%), and our subsequent increase to >25% of all failures during the shortage is notable. ^{Reference Rhee, Filbin and Massaro6}

While the majority of BCx failures pre-shortage were due to patients receiving antibiotics shortly before BCx obtainment, the proportion due to no BCx increased during the shortage. For most patients where BCx were not obtained, it is unlikely positive BCx results would have changed clinical management. Only two patients in our study may have benefited from BCx, with one of them having BCx ordered but were not obtained, suggesting a process failure rather than an issue with BCx stewardship. Situations in which no BCx were obtained during the shortage may have represented conscious decisions by clinicians to conserve BCx supply using evidence-based BCx stewardship guidance, yet they resulted in SEP-1 failures. A multicenter hospital network decreased BCx use by >20% during the shortage without a significant change in sepsis-related mortality, suggesting BCx reduction is safe. ^{Reference Shelly, Kunz, Mittal, Corwin, Chapman and Ender7}

BCx are the gold standard for detecting bloodstream infection and can be invaluable for targeting antibiotics and identifying potential sources of infection, especially in undifferentiated sepsis. However, identification of bloodstream infection does not always result in altered clinical management and even in sepsis may be low yield compared to site-specific cultures. For example, in pyelonephritis, BCx yield is 20–50%, whereas the yield of a urine culture is >95%; concordance between blood and urine cultures exceeds 93%. ^{Reference Fabre, Sharara, Salinas, Carroll, Desai and Cosgrove3} Additionally, uncomplicated gram-negative bacteremia and pyelonephritis can both be treated with 7 days of antibiotics with oral transition, so antibiotic management rarely changes even with positive BCx. ^{Reference Nelson, Aslan and Beahm8} Guidelines recommend BCx and intra-abdominal cultures in patients with community-acquired peritonitis related to a perforated viscus with hemodynamic instability and fever. ^{Reference Bonomo, Humphries and Abrahamian9} Peritoneal culture yield is significantly higher than BCx in one study: 69% and 11%, respectively. ^{Reference Jang, Lee, Shim, Choi, Yong and Lee10} In addition, BCx results are usually monomicrobial, while peritoneal culture are more frequently polymicrobial, suggesting BCx are inadequate assessments of the causative pathogens. ^{Reference Alqarni, Kantor and Grall11} Thus, clinicians can effectively treat these syndromes without BCx if alternative cultures are obtained. One concern with not obtaining BCx in sepsis may be if the initial suspected diagnosis is incorrect or if alternative cultures are not obtained in a timely manner. When the diagnosis is apparent, clinicians should be given the opportunity to practice high-value care by conserving resources rather than fear penalization by CMS. If sepsis mimickers can be identified readily, this obviates the need for BCx or antibiotic therapy. ^{Reference Rhee, Chiotos and Cosgrove2}

Diagnostic stewardship interventions focus on improving patient outcomes, requiring a balance between decreasing unnecessary use and optimizing yield. Unnecessary BCx are associated with patient harm, waste of resources, and even when positive, do not consistently change management. ^{Reference Fabre, Sharara, Salinas, Carroll, Desai and Cosgrove3} However, severely ill patients (e.g., in septic shock) warrant rapid assessment and antibiotic administration. These two competing priorities must be balanced in the creation of metrics such as SEP-1. Unfortunately, the evidence supporting SEP-1 improving outcomes in sepsis without shock is lacking, with IDSA recommending SEP-1 be limited to septic shock alone. ^{Reference Rhee, Chiotos and Cosgrove2} We believe our data similarly supports re-evaluating BCx requirements in SEP-1, as its mandates may limit diagnostic stewardship efforts and clinician autonomy.

Limitations include small sample size of SEP-1 cases from a single hospital system. Formal statistics or trend analyses were not performed due to the sample size and limited shortage duration. Retrospective adjudication of BCx necessity is challenging, as BCx are the only way to define bacteremia. Missing bacteremia may result in shorter than recommended antibiotic durations, which was observed in this cohort. However, the absence of recurrent infections in most patients suggests that bacteremia was either not present or was adequately treated. Analyses of overall effects of the BCx shortage on sepsis-related mortality were not assessed. Further studies of the relationship between BCx stewardship and SEP-1 metrics in a larger cohort would be beneficial.

We observed an increase in SEP-1 failures during the BCx shortage, likely driven by efforts to reduce BCx use. Use of alternative culture sites with higher yield than BCx resulted in SEP-1 failures that did not result in patient harm, a situation that other institutions may experience when implementing similar BCx stewardship recommendations. We believe SEP-1 should be re-evaluated, as BCx are not the only means of diagnosing the microbiologic etiology of infections and are low yield in select patients with sepsis and defined infectious or non-infectious syndromes.