Use of Daptomycin to Manage Severe MRSA Infections in Humans

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owi...

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Main Authors: Marco Fiore, Aniello Alfieri, Daniela Fiore, Pasquale Iuliano, Francesco Giuseppe Spatola, Andrea Limone, Ilaria Pezone, Sebastiano Leone
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/6/617
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author Marco Fiore
Aniello Alfieri
Daniela Fiore
Pasquale Iuliano
Francesco Giuseppe Spatola
Andrea Limone
Ilaria Pezone
Sebastiano Leone
author_facet Marco Fiore
Aniello Alfieri
Daniela Fiore
Pasquale Iuliano
Francesco Giuseppe Spatola
Andrea Limone
Ilaria Pezone
Sebastiano Leone
author_sort Marco Fiore
collection DOAJ
description Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owing to its rapid bactericidal activity and favourable safety profile. In this narrative review, we examine studies published between 2010 and April 2025. The data suggest that treatment with high-dose (8–10 mg kg⁻<sup>1</sup>) DAP shortened the time to blood-culture sterilisation by a median of 2 days compared with standard-dose vancomycin without increasing toxicity when model-informed area-under-the-curve monitoring was employed. Particular attention is given to the synergistic effects of DAP combined with fosfomycin or β-lactams, especially ceftaroline and ceftobiprole, in overcoming persistent and refractory MRSA infections; this approach results in a reduction in microbiological failure relative to monotherapy. Resistance remains uncommon (<2% of isolates), but recurrent mutations in <i>mprF</i>, <i>liaFSR</i>, and <i>walK</i> underscore the need for proactive genomic surveillance. Despite promising preclinical and clinical evidence supporting combination strategies, further randomized controlled trials are necessary to establish their definitive role in clinical practice, as are head-to-head cost-effectiveness evaluations. DAP remains a critical option in the evolving landscape of MRSA management, provided its use is integrated with precision dosing, resistance surveillance, and antimicrobial-stewardship frameworks.
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spelling doaj-art-c33caef8e2ce4cfb92eaea168f487c332025-08-20T02:24:30ZengMDPI AGAntibiotics2079-63822025-06-0114661710.3390/antibiotics14060617Use of Daptomycin to Manage Severe MRSA Infections in HumansMarco Fiore0Aniello Alfieri1Daniela Fiore2Pasquale Iuliano3Francesco Giuseppe Spatola4Andrea Limone5Ilaria Pezone6Sebastiano Leone7Department of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Women, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyAnesthesia and Intensive Care Unit, ASUR Marche, Area Vasta n. 4, Via Murri, 63023 Fermo, ItalyDepartment of Internal Medicine, Infectious Diseases Section, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100 Avellino, ItalyDepartment of Internal Medicine, Infectious Diseases Section, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100 Avellino, ItalyDepartment of Internal Medicine, Infectious Diseases Section, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100 Avellino, ItalyDepartment of Pediatrics, “San Giuseppe Moscati” Hospital, 81031 Aversa, ItalyDepartment of Internal Medicine, Infectious Diseases Section, San Giuseppe Moscati Hospital, Contrada Amoretta, 83100 Avellino, ItalyMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owing to its rapid bactericidal activity and favourable safety profile. In this narrative review, we examine studies published between 2010 and April 2025. The data suggest that treatment with high-dose (8–10 mg kg⁻<sup>1</sup>) DAP shortened the time to blood-culture sterilisation by a median of 2 days compared with standard-dose vancomycin without increasing toxicity when model-informed area-under-the-curve monitoring was employed. Particular attention is given to the synergistic effects of DAP combined with fosfomycin or β-lactams, especially ceftaroline and ceftobiprole, in overcoming persistent and refractory MRSA infections; this approach results in a reduction in microbiological failure relative to monotherapy. Resistance remains uncommon (<2% of isolates), but recurrent mutations in <i>mprF</i>, <i>liaFSR</i>, and <i>walK</i> underscore the need for proactive genomic surveillance. Despite promising preclinical and clinical evidence supporting combination strategies, further randomized controlled trials are necessary to establish their definitive role in clinical practice, as are head-to-head cost-effectiveness evaluations. DAP remains a critical option in the evolving landscape of MRSA management, provided its use is integrated with precision dosing, resistance surveillance, and antimicrobial-stewardship frameworks.https://www.mdpi.com/2079-6382/14/6/617methicillin-resistant <i>Staphylococcus aureus</i>daptomycinantibiotic resistancecombination therapybacteremia
spellingShingle Marco Fiore
Aniello Alfieri
Daniela Fiore
Pasquale Iuliano
Francesco Giuseppe Spatola
Andrea Limone
Ilaria Pezone
Sebastiano Leone
Use of Daptomycin to Manage Severe MRSA Infections in Humans
Antibiotics
methicillin-resistant <i>Staphylococcus aureus</i>
daptomycin
antibiotic resistance
combination therapy
bacteremia
title Use of Daptomycin to Manage Severe MRSA Infections in Humans
title_full Use of Daptomycin to Manage Severe MRSA Infections in Humans
title_fullStr Use of Daptomycin to Manage Severe MRSA Infections in Humans
title_full_unstemmed Use of Daptomycin to Manage Severe MRSA Infections in Humans
title_short Use of Daptomycin to Manage Severe MRSA Infections in Humans
title_sort use of daptomycin to manage severe mrsa infections in humans
topic methicillin-resistant <i>Staphylococcus aureus</i>
daptomycin
antibiotic resistance
combination therapy
bacteremia
url https://www.mdpi.com/2079-6382/14/6/617
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