ABSTRACT
Background: The objectives of this study were to describe the changing epidemiology of gram-negative infective endocarditis (GNIE) and to identify factors associated with treatment failure and death. Methods: Adult patients with GNIE were included if they met modified Duke criteria for definitive infective endocarditis (IE) between April 2010 and December 2021. Patients were identified using Boolean search terms. Clinical failure was a defined as a composite of all-cause 42-day mortality or microbiologic failure. All analyses were performed using Stata, version 15.1. Results: One-hundred twenty-three patients were included. The most common pathogens were Serratia spp. (43%), Pseudomonas aeruginosa (21%), and Klebsiella spp. (14%). Fifty-two percent of cases were among persons who injection drugs (PWID; n = 64), for whom Serratia spp. (70%) was the most common cause of GNIE. Overall, patients infected with P. aeruginosa had higher microbiologic failure rates than other patients (23% vs 6%; P = .004). Patients who received combination therapy (n = 53) had comparable median lengths of stay (23 vs 19.5 days; P = .412), microbiologic failure rates (11.3% vs 7.1%; P = .528), clinical failure rates (18.9% vs 22.9%; P = .592), and 90-day mortality rates (13.2% vs 25.7%; P = .088) as those treated with monotherapy. After applying stepwise logistic regression, male gender, Pitt Bacteremia Score, and not receiving surgical intervention despite a surgical indication were associated with clinical failure. Conclusions: This is the first study to identify Serratia spp. as the most common etiology of GNIE, which was particularly true among PWID. Microbiologic failures occurred most commonly among P. aeruginosa, and use of combination antimicrobial therapy did not improve clinical outcomes.
ABSTRACT
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.