Our results showed that comparing to BSI patients in the non-ESBL group, the ESBL group had greater risks of empirical medication failure and mortality, prolonged hospital stay, and incurred more medical costs. After excluding confounding factors, there were still statistically significant differences in effective empirical antimicrobial therapy rate, length of hospitalization and hospitalization costs between the two groups.
We believe that the exclusion of confounding factors and the inclusion of more comprehensive economic indicators in retrospective studies through chronological order and causality can more accurately reflect the impact of ESBL-producing pathogens on the economic burden of patients. When calculating the economic burden, we used hospital expenses, which are more comprehensive than patient bills, to reflect the impact of ESBL-producing pathogens on the entire medical system, and included DALYs to calculate the overall burden on patients’ families and society brought about by the lack of labor due to diseases [36].
Similar to most of the studies in the article counted by Zhen X et al. in a recent systematic review [13], patients in the ESBL group in our study had longer hospital stays and higher financial burden. We found a 33.3% increase in median post-bacteremia LOS (from 9 days to 12 days), a 28.6% increase in total LOS (from 14 days to 18 days), and a 36.3% increase in hospital costs (an additional $2047 per patient) in the post-PSM ESBL group.
At present, how ESBL affects the burden of disease is still unclear. Most scholars agree that ESBL-induced prolonged hospitalization is an important reason for the increase in hospitalization costs. However, the contribution of the initial treatment effectiveness and the direct cost of antibiotics to the overall direct burden is still controversial. We believe that this can be related to the comparison of medical services and drug prices in different regions[13]. The results of the mediation effect test in this study we found that ESBL had statistically significant effects on IEAT and LOS, and these variables, in turn, have significant effects on hospitalization costs, suggesting that interventions aimed at modifying ESBL might indirectly influence costs through changes in IEAT and LOS. We suggest that addressing and studying the mediators can give more insight into the mechanism through which ESBL influences hospitalization costs. In our study, the median difference in antimicrobial spending accounted for 21.2% (434/2037) of the median difference in total hospitalization spending, and the higher cost of antimicrobials in the ESBL group and its share in Western medicine (27.3% vs 39%, p = 0.002) suggested that the higher cost of drugs required for ESBL-BSI itself also increased hospitalization costs.
In this study, we observed that in the composition of the disease burden, in the average disability years (1.84–2.12 years), the average hospitalization days of 14–18 days produced less than 1% of the YLDs of the DALYs after the weight of the disease was assigned. We think that this is normal due to the short Disease-process of bloodstream infection and the high mortality rate. We suggest that for investigators with no access to complete data, the use of YLDs alone in the absence of bacteremia-associated sequelae is sufficient to approximately reflect the burden of disease in adults with acute bloodstream infections.
In this study, we observed that clinicians' decisions to use carbapenems were not random(non-ESBL = 45.4% vs ESBL = 53%, p = 0.039). However, after excluding the interference of SOFA score and APACHE II score, there was no significant difference in the drug usage rate between the two groups༈p = 0.153༉. We speculate that this may be due to the fact that doctors used the drug according to the severity of clinical symptoms rather than risk factors caused by ESBL before obtaining the drug sensitivity report. When inquiring medical records, we found that most of the electronic admission records did not record the antibacterial drug use information in the six months before admission. This is concerning, since some reports suggest that the use of antibacterial drugs other than β-lactams is also a risk factor for ESBL[17]. Therefore, we believe that it is necessary to trace and record all antimicrobial drugs in detail during admission consultation for more refined antimicrobial stewardship (AMS).
In previous studies, nosocomial infection was usually a high-risk factor for ESBL-producing bacterial infection [37]. However, in this study, although the LOS of the ESBL group before PSM was longer, there was no significant difference in the nosocomial infection rate between the two groups (non-ESBL = 40.1% vs ESBL = 35.5%, p = 0.399), suggesting that blaESBL in this area has been widely spread in the community. Combining the relatively high ESBL detection rate in the local area and, clinicians should carefully choose to use third-generation cephalosporins before obtaining definite drug susceptibility results [7][35]. There are also studies in China showing that choosing antimicrobial agents covering ESBL-producing bacteria as empirical antibiotic therapy can improve the cure rate, reduce the direct and indirect costs for individual and society, clinics need to balance individual and social needs [31]. We believe that the ESBL detection tricycle plan and AWaRe tool recommended by WHO should be better implemented, and a multi-dimensional molecular epidemiological early warning and antimicrobial stewardship system should be established to face the comprehensive and multidisciplinary health challenge of antimicrobial resistance [38][39].
Although we ruled out the confounding interference of different indicators, there may still be potential selection biases. Since the Charlson score assigned different weights to the disease, in order to maximize the enrollment rate of patients in the PSM, we did not include a single comorbidity in the pairing criteria in the PSM. Previous literature pointed out that ESBL plasmids may be related to some virulence factors[40], but this study only considered the interference of drug resistance genes on patients, and potential interference factors such as virulence factors were eliminated by incorporating indicators such as SOFA score into PSM matching.
In summary, we support the notion that bloodstream infection from ESBL-producing EC/KP led to reduced efficacy of empiric medication, prolonged hospital stays, and increased patient financial burden. This study suggests that a reasonable assessment of ESBL risk and precise use of antibiotics are very important in reducing the burden on patients. Finally, we believe that continuous epidemiological detection and risk assessment of antimicrobial resistance is necessary for clinical and antimicrobial stewardship.