Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Diagnostic Testing and Antibiotic Utilization in Patients with COVID-19

Background Patients with COVID-19 receive high rates of antibiotic therapy, despite viral origin of infection. Reports of bacterial coinfection range from 3.5 to 8% in the early phase of infection. This study aimed to evaluate the relationship between diagnostic tests and antibiotic utilization in patients admitted with COVID-19 at the University of Maryland Medical Center to better inform future prescribing practices. Methods Retrospective cohort study of adult patients with a positive SARS-CoV-2 PCR on admission from March 2020 through June 2020. Associations between diagnostic tests employed and antibiotic initiation and duration were explored using bivariate analysis (SPSS®). Results Baseline characteristics of 224 included patients are reported in Table 1. Excluding SARS-CoV-2 PCRs, most frequently performed diagnostic tests included blood cultures (65.6%), MRSA nasal surveillance (45.1%), respiratory cultures (36.2%), respiratory viral panel (RVP) (33.0%), and Legionella (28.6%) and pneumococcal (26.3%) urine antigens. Positivity of RVP, Legionella, pneumococcus, blood, and respiratory tests were low (1.3%, 0.4%, 0.9%, 1.8%, and 6.7%, respectively). A total of 62% of patients were initiated on antibacterial therapy with a median cumulative antibiotic duration of 77.9 hours (IQR 41.4, 111.8). History of chronic respiratory disease (76% vs. 58.6%;P=0.025), any degree of oxygen requirement on admission (72% vs. 42.6%;P=0.006), and performance of blood cultures (70.7% vs. 46.8%, P< 0.0001) were associated with antibiotic initiation. Positive bacterial diagnostic respiratory culture (median duration 72.8h [IQR 46.7, 96.6] vs. 97.3h [IQR 79.8, 194.1];P=0.027) and positive blood culture (median duration 80.1h [IQR 42.1, 111.7] vs. 97.5h [IQR 71.8, 164.8];P=0.046) were associated with longer antibiotic duration. Patients who did not have respiratory cultures performed had similar antibiotic durations as those with negative respiratory cultures. Table 1. Baseline Characteristics Conclusion Despite low coinfection rates, negative diagnostic tests did not result in shorter empiric antibacterial duration. These findings highlight the ongoing need for both diagnostic and antimicrobial stewardship in COVID-19. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)

Coronavirus disease 2019 (COVID-19) research agenda for healthcare epidemiology.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Change in hospital antibiotic use and acquisition of multidrug-resistant gram-negative organisms after the onset of coronavirus disease 2019.

Interrupted time series segmented regression was conducted to trend antibiotic use and multidrug-resistant gram-negative (MDRGN) acquisition relative to COVID-19 in an academic hospital. Total antibiotic use and antibiotic use related to pneumonia was higher in the period after the onset of COVID-19 compared to the similar calendar period in 2019. Furthermore, MDRGN acquisition increased 3% for every increase in positive COVID-19 tests per week.