Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis.

BACKGROUND: Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients. METHODS: Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018-2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS). RESULTS: Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16-1.43, P < 0.0001]) and longer hospital LOS (14.8 vs. 13.3, P < 0.0001). Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality for ENT (P = 0.0182) and PsA (P = 0.0249) and significantly longer post-culture LOS for ENT (P < 0.0001) and PsA (P < 0.0001). CONCLUSIONS: Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens.

Catheter-associated urinary tract infections (CAUTIs) and non-CAUTI hospital-onset urinary tract infections: Relative burden, cost, outcomes and related hospital-onset bacteremia and fungemia infections.

OBJECTIVE: To describe the relative burden of catheter-associated urinary tract infections (CAUTIs) and non-CAUTI hospital-onset urinary tract infections (HOUTIs). METHODS: A retrospective observational study of patients from 43 acute-care hospitals was conducted. CAUTI cases were defined as those reported to the National Healthcare Safety Network. Non-CAUTI HOUTI was defined as a positive, non-contaminated, non-commensal culture collected on day 3 or later. All HOUTIs were required to have a new antimicrobial prescribed within 2 days of the first positive urine culture. Outcomes included secondary hospital-onset bacteremia and fungemia (HOB), total hospital costs, length of stay (LOS), readmission risk, and mortality. RESULTS: Of 549,433 admissions, 434 CAUTIs and 3,177 non-CAUTI HOUTIs were observed. The overall rate of HOB likely secondary to HOUTI was 3.7%. Total numbers of secondary HOB were higher in non-CAUTI HOUTIs compared to CAUTI (101 vs 34). HOB secondary to non-CAUTI HOUTI was more likely to originate outside the ICU compared to CAUTI (69.3% vs 44.1%). CAUTI was associated with adjusted incremental total hospital cost and LOS of $9,807 (P < .0001) and 3.01 days (P < .0001) while non-CAUTI HOUTI was associated with adjusted incremental total hospital cost and LOS of $6,874 (P < .0001) and 2.97 days (P < .0001). CONCLUSION: CAUTI and non-CAUTI HOUTI were associated with deleterious outcomes. Non-CAUTI HOUTI occurred more often and was associated with a higher facility aggregate volume of HOB than CAUTI. Patients at risk for UTIs in the hospital represent a vulnerable population who may benefit from surveillance and prevention efforts, particularly in the non-ICU setting.

Hospital mortality and length of stay associated with Enterobacterales positive blood cultures: a multicenter analysis.

Delayed time to antimicrobial susceptibility results can impact patients' outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57-65 h and >65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.