BACKGROUND/RATIONALE:
Approximately 0.7 to 1.7 million health care-associated infections (HAIs) occur in the U.S. each year in inpatients receiving care in U.S. acute care hospitals. Many of these infections are caused by antibiotic resistant organisms including multidrug resistant gram-negative organisms (MDRGNOs). One of the prime predictors of morbidity and mortality following infection with drug resistant organisms is inadequate empiric and definitive antibiotic treatment of the infection. Lack of specific clinical practice guidelines for treatment of these organisms increases the ambiguity of effective treatment strategies. It is unclear what treatment regimens are being used within VA for treatment of MDRGNOs or how effective they are. Therefore, the goal of this study is to use national VA data to describe current treatment strategies for select MDRGNOs (Carbapenem Resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter species) and the comparative effectiveness of these strategies on outcomes in Veterans. This study is highly relevant to patients seeking care in VA, as Veterans experience many of the risk factors associated with development of an MDRGNO infection. VA treats patients with serious complex conditions that require frequent hospitalization or contact with health care or use of invasive devices (i.e. spinal cord injury, amputations) that put them at risk for infections. MDRGNOs and inadequate treatment have a significant impact on morbidity and mortality outcomes in those with complex conditions.

OBJECTIVE(S):
The objectives of this Antimicrobial Comparative Effectiveness study, known as ACE are to: a) Describe antibiotic treatment strategies utilized to treat MDRGNOs (CRE, P. aeruginosa, and Acinetobacter sp.) in Veterans; b) Compare the effectiveness of common empiric antibiotic treatment strategies, including monotherapy versus combination therapy, on treatment failure, in-hospital mortality, and 30-day case fatality for each MDRGNO category; and c) Compare the impact of treatment strategies on the development of Clostridium difficile infection (CDI), and conduct a cost-effectiveness analysis of the most frequent or effective antibiotic treatment strategies for each MDGRNO category.

METHODS:
The ACE study will involve a retrospective comparative effectiveness analysis of national VA medical, encounter, pharmacy, and microbiology laboratory data January 1, 2012-December 31, 2017 from patients hospitalized at any VA facility. We will also conduct a chart review of a sample of cases to ensure accurate identification of infections.
All adult patients admitted to an inpatient VA unit during the study period will be included. To ensure infection versus colonization, the main analysis will only include those patients identified with bloodstream infections (BSIs) through positive blood cultures. We will include three cohorts of patients: 1) those infected with CRE (Klebsiella sp., Escherichia coli, Enterobacter sp. only as based on VA definitions); 2) those infected with P. aeruginosa (multidrug resistant [MDR] and non-MDR); and 3) those infected with MDR or extensively drug-resistant
(XDR) Acinetobacter. We expect to include over 5,000 patients with the strict positive blood culture criteria. A secondary analysis will use a less restrictive definition including all positive blood, urine, and sputum cultures; which we expect to include over 50,000 patients.

FINDINGS/RESULTS:
The expected outcomes of ACE will include a characterization of current treatment approaches for MDRGNOs in VA and a determination of which regimens are more effective for outcomes and costs.

IMPACT:
Our findings will produce effectiveness data on outcomes for MDRGNOs including CRE in a diverse population of Veterans that can be used by VA program offices for developing guidance for treatment to improve the effectiveness of treatment and healthcare of patients with MDRGNO infections across different populations.

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External Links for this Project

NIH Reporter

Grant Number: I01HX002169-01A2
Link: https://reporter.nih.gov/project-details/9502631

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PUBLICATIONS:

Journal Articles

1. Wilson GM, Fitzpatrick MA, Suda KJ, Smith BM, Gonzalez B, Jones M, Schweizer ML, Evans M, Evans CT. Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans. JAC-antimicrobial resistance. 2022 Oct 1; 4(5):dlac106. [view]
2. Fitzpatrick MA, Suda KJ, Poggensee L, Vivo A, Wirth M, Wilson G, Evans M, Evans CT. Epidemiology and clinical outcomes associated with extensively drug-resistant (XDR) in US Veterans' Affairs (VA) medical centers. Infection control and hospital epidemiology. 2021 Mar 1; 42(3):305-310. [view]
3. Wilson GM, Fitzpatrick MA, Walding K, Gonzalez B, Schweizer ML, Suda KJ, Evans CT. Evaluating the clinical effectiveness of new beta-lactam/beta-lactamase inhibitor combination antibiotics: A systematic literature review and meta-analysis. Antimicrobial stewardship & healthcare epidemiology : ASHE. 2021 Nov 25; 1(1):e53. [view]
4. Ramanathan S, Albarillo FS, Fitzpatrick MA, Suda KJ, Poggensee L, Vivo A, Evans ME, Jones M, Safdar N, Pfeiffer C, Smith B, Wilson G, Evans CT. Infectious Disease Consults of Bloodstream Infection and Impact on Health Outcomes. Open forum infectious diseases. 2022 Sep 1; 9(9):ofac456. [view]
5. Wilson GM, Fitzpatrick M, Walding K, Gonzalez B, Schweizer ML, Suda KJ, Evans CT. Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug-Resistant Gram-Negative Infections. Open forum infectious diseases. 2021 Feb 1; 8(2):ofaa651. [view]
6. Fitzpatrick MA. Real-world antibiotic needs for resistant Gram-negative infections. The Lancet. Infectious diseases. 2020 Oct 1; 20(10):1108-1109. [view]
7. Fitzpatrick MA, Suda KJ, Poggensee L, Vivo A, Wilson G, Jones MM, Evans M, Safdar N, Evans CT. Treatment of extensively-drug resistant (XDR) Acinetobacter and impact on clinical outcomes in U.S. veterans affairs (VA) medical centers. American journal of infection control. 2022 Sep 1; 50(9):1020-1025. [view]
8. Suda KJ, Traversa A, Patel U, Poggensee L, Fitzpatrick MA, Wilson GM, Evans CT. Uptake in newly approved antibiotics prescribed to patients with carbapenem-resistant Enterobacterales (CRE). Infection control and hospital epidemiology. 2023 Apr 1; 44(4):674-677. [view]

DRA: Infectious Diseases
DRE: Treatment - Observational, TRL - Applied/Translational, Treatment - Comparative Effectiveness
Keywords: Comparative Effectiveness, Effectiveness, Practice Patterns/Trends
MeSH Terms: none