1982. Epidemiology and Clinical Outcomes of non-HACEK Gram-negative Infective Endocarditis
Authors: Shah Sunish , Clarke Lloyd , Shields Ryan K 
Published: December 2022

Abstract

Background
Infective endocarditis (IE) due to non-HACEK Gram-negative (GN) pathogens is rare, but optimal treatment has not yet been defined. The objective of this study was to report the epidemiology, clinical characteristics, and outcomes of GNIE across our health system.

Methods
Adult patients with GNIE were identified between April 2010 through December 2021 and included if they met DUKE criteria for definitive IE. Patients with persistently positive blood cultures for Gram-positive pathogens or yeast were excluded if valve cultures did not grow GN bacteria. Clinical failure was defined as a composite of all-cause mortality or microbiologic failure at day 42. Microbiologic failure was defined as an escalation of antimicrobial therapy after emergence of resistance, increased vegetation size, or failure to clear blood cultures by day 14.

Results
Overall, 123 patients were included. GN pathogens included Serratia spp. (43%), P. aeruginosa (21%), Klebsiella spp. (14%), and other GN bacteria (22%) (Figure). 64 (52%) cases were among persons who inject drugs (PWID) (Table 1). GNIE secondary to Serratia spp. was more common in PWID compared to other pathogens (85% vs 27%; P&lt; 0.001). Microbiologic failure was more common for P. aeruginosa than other pathogens (23% vs 5%; P=0.004). A stepwise multivariate logistic regression model identified age, PITT bacteremia score, and duration of positive blood cultures as independent predictors of clinical failure (Table 2). Patients who received &gt; 72 hours of combination therapy (n=53) had a comparable length of stay (23 days vs 19.5; P=0.412), microbiologic failure rate (11.3% vs 7.1%, P=0.528), clinical failure rate (18.9% vs 22.9%, P=0.592), and 90-day mortality rate (13.2% vs 25.7%, P=0.088) to those who did not receive combination therapy. 80% (4/5) of patients who experienced 30-day readmission secondary to an antimicrobial adverse event received combination therapy.
Table 1: Epidemiology and Overview CCI: Charleson Comorbidity Index; MDR: Multiple drug resistance; VGS: Viridans Group Streptococcus spp. #S. marcescens (n=50); S. liquefasciens (n=2); undifferentiated species (n=1) *K. pneumoniae (n=11); K. oxytoca (n=5); K. variicola (n=1); E. coli (n=12); P. mirabilis (n=3); P. vulgaris (n=1); E. cloacae complex (n=2); E. aerogenes (n=1) ^B. cepacia (n=2); S. maltophillia (n=2); A. lwoffi (n=2); P. stutzeri (n=1); A. baumanni (n=1) Table 2: Multivariate Logistic regression for factors associated with 42-day failure

Conclusion
To our knowledge this is the largest cohort of patients with non-HACEK GNIE, and the first to identify Serratia spp. to be the most common etiology of GNIE, particularly among PWID. Microbiologic failures occurred commonly among P. aeruginosa. Overall, we did not identify a clinical benefit to combination therapy; additional studies are needed to validate these findings.

Disclosures
Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.