Wilson, Brigid

Abstract Background Reductions in the use of broad-spectrum antibiotics is a cornerstone of antimicrobial stewardship. We aim to demonstrate use of the Desirability of Outcome Ranking Approach for the Management of Antimicrobial Therapy (DOOR MAT) to evaluate the treatment of Escherichia coli and Klebsiella pneumoniae bloodstream infections in patients from the Veterans Health Administration (VHA) across a decade. Methods Using electronic records, we determined empiric and definitive antibiotic treatments, clinical characteristics, and 30-day mortality of patients with monomicrobial E. coli and K. pneumoniae bloodstream infections hospitalized in VHA medical centers from 2009 to 2018. Focusing on patients treated with parenteral β-lactams and with available antibiotic susceptibility testing results, we applied a range of DOOR MAT scores that reflect the desirability of antibiotic choices according to spectrum and activity against individual isolates. We report trends in resistance and desirability of empiric and definitive antibiotic treatments. Results During the 10-year period analyzed, resistance to expanded-spectrum cephalosporins and fluoroquinolones increased in E. coli but not in K. pneumoniae, while resistance to carbapenems and piperacillin-tazobactam remained unchanged. In 6451 cases analyzed, we observed improvements in DOOR MAT scores consistent with deescalation. Improvement in desirability of definitive treatment compared with empiric treatment occurred in 26% of cases, increasing from 16% in 2009 to 34% in 2018. Reductions in overtreatment were sustained and without negative impact on survival. Conclusions DOOR MAT provides a framework to assess antibiotic treatment of E. coli and K. pneumoniae bloodstream infections and can be a useful metric in antimicrobial stewardship.

Abstract Background Achieving appropriate therapy for BSI caused by Gram-negative rods (GNR) is challenging. The availability of AST results allows de-escalation from broad- to narrow-spectrum agents. De-escalation is a goal of antimicrobial stewardship (AS). Through the analysis of inpatient BL antibiotic regimens in a nationwide cohort of patients with Escherichia coli and Klebsiella pneumoniae BSI, we compared the relative spectrum of empiric and definitive treatments to AST results and identified opportunities for de-escalation. Methods Using a cohort of patients hospitalized within VHA, we identified patients with a blood culture positive for E. coli or K. pneumoniae between 2006 and 2015. We analyzed the subset of patients receiving inpatient BLs before and after Gram stain (GS) and AST results. BLs were grouped into five tiers of increasing spectrum, both with and without a requirement for anaerobic activity (Figure 1). Tiers of BLs across the treatment periods were summarized and compared with the lowest-spectrum tier with an active agent. Rates of inactive, optimal, and overly broad BL therapy were summarized by organism and treatment period. Results Of 36,531 BSI identified, we analyzed a subset of 10,825 (7,100 E. coli, 3,725 K. pneumoniae) that met our inclusion criteria (Figure 2). The use of inactive BL agents decreased across time, falling from 11% in early empiric to 4.5% in definitive treatments. The proportion of patients receiving the narrowest available effective BL therapy (“optimal” therapy) increased from 5% to 8% after GS results and to 14% after AST results (Figure 3). De-escalation to optimal therapy after AST results was observed in only 7% of opportunities. If anaerobic activity was required, a smaller proportion of cases would be considered overtreated in the empiric periods (45–46%), but de-escalation after AST results was observed in only 10% of these cases. Conclusion Changes in BL agents across treatment periods reflect an escalation to active treatment, but the absence of de-escalation after AST results was available. This was true both with and without considering a need for anaerobic activity. Expansion of this analysis to include additional classes such as fluoroquinolones may reveal opportunities for AS and de-escalation to optimal therapy in the treatment of E. coli and K. pneumoniae BSI. Disclosures R. Patel, CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Research grant – monies paid to Mayo Clinic. Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest and Genentech: Consultant and Scientific Advisor, Consulting fee – monies paid to Mayo Clinic. ASM and IDSA: Travel reimbursement and editor’s stipends, Travel reimbursement and editor’s stipends. NBME, Up-to-Date and the Infectious Diseases Board Review Course: Varies, Honoraria. Mayo Clinic: Employee, Salary. R. Banerjee, Accelerate Diagnostics, Biomerieux, BioFire: Grant Investigator, Research grant and Research support.

AbstractBackgroundOvercoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa.MethodsIn this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).ResultsWe found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA).ConclusionsThe diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.