Discussion

In this multicenter database encompassing almost 800,000 hospitalized adult patients, there were ∼4 times as many non-CLABSI HOB cases as CLABSI cases (1,574 vs 403) using a conservative EHR-based case definition that only included the first positive blood culture with a CDC-designated BSI pathogen. ^{Reference Yu, Ye and Edwards8} Compared with matched controls, both CLABSIs and non-CLABSI HOB cases were associated with increases in LOS and significantly higher hospital costs, mortality rates, and 30-day readmission rates. Rock et al ^{Reference Rock, Thom and Harris4} reported that among ICU patients, changes in HOB rates are highly associated with changes in CLABSI rates. These data suggest that it is feasible for HOB to serve as a quality metric indicator while including more BSI patients than the current CLABSI-reportable events, and that such a change may be consequential. Thus, we highlight 2 key points: (1) the extra cost of care required for CLABSI and non-CLABSI HOB cases and (2) the hospital stay, mortality burden, and readmission risk related to both. Reducing HOB and/or improving time to definitive therapy through the existing required infrastructures of infection prevention and antimicrobial stewardship programs has the potential to improve patient safety. ^{Reference Hospital Association and Dickinson17}

Overall admission characteristics for CLABSI and non-CLABSI HOB were generally similar, although the CLABSI cohort had a higher rate of ICU encounters (73.4% vs 62.1%). Probably due to criteria used for the CLABSI designation, which exclude cases related to another infection, ³ non-CLABSI HOB cases were more likely to have another positive culture, most commonly urine or respiratory, and to be associated with other reportable HAIs (CAUTI or SSI). Although our study was not designed to definitively evaluate the sources of HOB, we found that 27.4% of all HOB admissions had other positive cultures with the same microorganism found in the blood culture within the specified time frame. Notably, we evaluated urinary, respiratory, and skin and soft-tissue cultures, but we did not include other sources potentially associated with HOB, including the gastrointestinal system, ^{Reference Dantes, Abbo and Anderson6,Reference Mortensen, Mygind and Schønheyder18,Reference Leekha, Robinson and Jacob19} or poorly or nondocumented sources such as peripheral intravenous devices.

The designation of CLABSI is predicated on excluding temporal and clinical relationships to another culture site with the same pathogen. It is often difficult to differentiate secondary versus primary infection; this distinction is no longer relevant for HOB. Removal of the requirement for attributing primary and secondary sources of infection may refocus attention on understanding factors driving HOB, which in turn may redirect emphasis to prevention or timely treatment of infections that may be a source of HOB, essentially bringing patient care back as the focus rather than whether the event is reportable or not.

Enterobacteriaceae was the most common bloodstream microorganism for non-CLABSI HOB, whereas CoNS was the most common bloodstream microorganism for CLABSI. Other common microorganisms included S. aureus and Enterococcus spp. These data are consistent with a recent analysis of pathogens associated with BSI in Ontario, which identified Escherichia coli as the most common pathogen. ^{Reference Verway, Brown and Marchand-Austin20} However, other studies have found a larger contribution by S. aureus and CoNS and a diminished role for Enterobacteriaceae. ^{Reference Dantes, Abbo and Anderson6,Reference Leekha, Robinson and Jacob19} The reasons for the different pathogen distributions among studies may be due to differences in patient populations and in case study parameters. For example, we excluded CDC commensal microorganisms from the HOB definition to be consistent with a recently published paper; ^{Reference Yu, Ye and Edwards8} however, commensals can be true pathogens depending on the number, proximity, and clinical interpretation of positive blood cultures. ^{Reference Matsuhisa, Kenzaka and Kobayashi21,Reference Pouget, Chatre and Lavigne22}

Our data support and update prior reports on the burden of HOB in hospitalized patients. The ∼30% mortality rate of HOB in our study is generally comparable to HOB mortality rates reported in other US hospitals ^{Reference Glied, Cohen, Liu, Neidell and Larson23,Reference Ridgway, Sun, Tabak, Johannes and Robicsek24} and in Denmark, ^{Reference Mortensen, Søgaard and Mygind25} and the mortality rate of 35.3% in patients with an ICU encounter is similar to the 36.6% reported in ICU admissions in France. ^{Reference Massart, Wattecamps, Moriconi and Fillatre26} The similarity of these data suggest that challenges in managing these infections transcend individual healthcare systems and case-mix differences; these infections remain a ubiquitous problem in healthcare that warrants a larger spotlight. The HOB LOS and costs reported here provide an important update to earlier US studies encompassing smaller numbers of hospitals ^{Reference Glied, Cohen, Liu, Neidell and Larson23,Reference Ridgway, Sun, Tabak, Johannes and Robicsek24} and focused on estimates for CLABSI costs. ^{Reference Bysshe, Gao and Heaney-Huls2,9} Significant increases in 30-day readmission rates compared with controls were observed for patients who did not have an ICU encounter, but not those with ICU admissions, perhaps suggesting that the complexity of managing HOB may impact the stability of patients at the time of discharge from a regular hospital ward.

This study had several limitations. The definition of HOB used by the NHSN may undergo further iteration as more is learned about its use in infection prevention. We evaluated non-CLABSI HOB to provide insights into the additional burden of BSI cases not captured by reportable CLABSI events. However, as noted earlier, only first positive blood cultures were considered eligible for HOB designation, so HOB prevalence may have been underestimated. For our exploration of associated positive cultures, microorganism identification was based on species only. More frequent culturing in ICU patients may have led to increased identification of microorganisms compared with non-ICU patients. In case-matched analyses, controls were matched to CLABSI cases but not to non-CLABSI HOB cases; however, analyses were adjusted to make outcome comparisons more similar. As with any case-matched analyses, we acknowledge that differential outcomes are highly dependent on the control population. However, sensitivity analyses in which ICU status was not considered as a matching criterion resulted in similar differences in outcomes. Finally, sources of HOB were assigned to categories that could be feasibly extracted from EHR. For example, quantification of secondary HOBs associated with peripheral IV lines was beyond the scope of this analysis. Future studies will be needed to delineate a more granular source attribution list for HOB to facilitate infection preventionist efforts to mitigate HOB events.

The findings from this study document the extensive burden associated with non-CLABSI HOB in hospitalized US patients. Expanding reporting metrics to include non-CLABSI HOB will help provide a more comprehensive view of BSI control in hospitals and may allow new approaches to reducing the rate of these consequential infections. As healthcare systems continue to adjust to financial ramifications of the COVID-19 pandemic, ^{27,Reference Wang, Witman and Cho28} demonstration of the economic and patient burdens of HOB will be important in vetting this outcome as a reportable hospital quality metric. In the process, this information will provide insights into opportunities for improved patient safety and reduced hospital costs beyond those associated with NHSN-reportable CLABSI events. ^{Reference Bysshe, Gao and Heaney-Huls2}