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

Abstract：

: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 in vitro and in vivo 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 Streptococcus parasanguinis (PEN MIC, 4 μg/ml) and was treated with vancomycin plus cardiac surgery. Case 2 was caused by Streptococcus mitis (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 in vitro studies, except for daptomycin-ampicillin, all combinations demonstrated both synergy and bactericidal activity against the S. parasanguinis isolate. Only PEN-gentamicin, daptomycin-gentamicin, and daptomycin-ampicillin demonstrated both synergy and bactericidal activity against the S. mitis strain. Both strains developed high-level daptomycin resistance (HLDR) during daptomycin in vitro passage. In the EE studies, PEN alone failed to clear S. mitis from vegetations, while ceftriaxone and vancomycin were significantly more effective (P < 0.001). The combination of gentamicin with PEN or vancomycin increased bacterial eradication compared to that with the respective monotherapies. In summary, two patients with highly PEN-R VGS IE were cured using vancomycin-based therapy. In vivo, regimens of gentamicin plus either β-lactams or vancomycin were more active than their respective monotherapies. Further clinical studies are needed to confirm the role of vancomycin-based regimens for highly PEN-R VGS IE. The emergence of HLDR among these strains warrants caution in the use of daptomycin therapy for VGS IE.

journal_name

Antimicrob Agents Chemother

journal_title

Antimicrobial agents and chemotherapy

authors

Pericàs JM,Nathavitharana R,Garcia-de-la-Mària C,Falces C,Ambrosioni J,Almela M,García-González J,Quintana E,Marco F,Moreno A,Bayer AS,Miró JM,Karchmer AW,Hospital Clínic Endocarditis Study Group.

doi

10.1128/AAC.00516-19

subject

Has Abstract

pub_date

2019-07-25 00:00:00

issue

eissn

0066-4804

issn

1098-6596

pii

AAC.00516-19

journal_volume

pub_type

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