Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens

Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combination...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2019-08, Vol.63 (8)
Main Authors: Pericàs, Juan M, Nathavitharana, Ruvandhi, Garcia-de-la-Mària, Cristina, Falces, Carles, Ambrosioni, Juan, Almela, Manel, García-González, Javier, Quintana, Eduard, Marco, Francesc, Moreno, Asunción, Bayer, Arnold S, Miró, José M, Karchmer, Adolf W
Format: Article
Language:English
Subjects:
Adult
Drug Resistance, Bacterial
Drug Resistance, Bacterial - drug effects
Endocarditis, Bacterial
Endocarditis, Bacterial - drug therapy
Endocarditis, Bacterial - microbiology
Experimental Therapeutics
Humans
Male
Middle Aged
Penicillins
Penicillins - therapeutic use
Vancomycin
Vancomycin - therapeutic use
Viridans Streptococci
Viridans Streptococci - drug effects
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Summary:Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations and The following combinations were tested by time-kill studies and in the rabbit experimental endocarditis (EE) model: PEN-gentamicin, ceftriaxone-gentamicin, vancomycin-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin. Case 1 was caused by (PEN MIC, 4 μg/ml) and was treated with vancomycin plus cardiac surgery. Case 2 was caused by (PEN MIC, 8 μg/ml) and was treated with 4 weeks of vancomycin plus gentamicin, followed by 2 weeks of vancomycin alone. Both patients were alive and relapse-free after ≥6 months follow-up. For the studies, except for daptomycin-ampicillin, all combinations demonstrated both synergy and bactericidal activity against the isolate. Only PEN-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin demonstrated both synergy and bactericidal activity against the strain. Both strains developed high-level daptomycin resistance (HLDR) during daptomycin passage. In the EE studies, PEN alone failed to clear from vegetations, while ceftriaxone and vancomycin were significantly more effective (  
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00516-19