Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis

• Published in: Antimicrobial agents and chemotherapy 2021-09, Vol.65 (10), p.e0252220-e0252220
• Main Authors: Cañas, María A, Téllez, Adrian, García de la Mària, Cristina, Dahl, Anders, García-González, Javier, Hernández-Meneses, Marta, Almela, Manel, Ambrosioni, Juan, Falces, Carlos, Quintana, Eduard, Vidal, Barbara, Perissinotti, Andres, Tolosana, José M, Sandoval, Elena, Pericàs, Juan M, Moreno, Asunción, Miró, José M
• Format: Article
• Language: English
• Subjects: Abiotrophia; Anti-Bacterial Agents - pharmacology; Antimicrobial Chemotherapy; Carnobacteriaceae; Daptomycin - pharmacology; Endocarditis, Bacterial - drug therapy; Humans; Susceptibility
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02522-20

and species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of and IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in , whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in and species . Resistance was stable, and most combination therapies did not prevent it.