The Evolving Reduction of Vancomycin and Daptomycin Susceptibility in MRSA—Salvaging the Gold Standards with Combination Therapy

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.

Panorama of Bacterial Infections Caused by Epidemic Resistant Strains

“…Therapeutic choices for MRSA infections take into account several factors, such as the resistance profile, risk factors, associated comorbidities, and response to previously used antibiotics. Thus, for most cases, vancomycin and daptomycin are the first choices; however, considering the VISA and VRSA strains, vancomycin has been little recommended [ 30 ].…”

Polymyxin and lipopeptide antibiotics: membrane-targeting drugs of last resort

“…As the use of polymyxins and daptomycin increases, it is likely that the frequency of resistance will increase [76,83]. However, monitoring the incidence of resistance is challenging because the definitions of polymyxin and lipopeptide resistance are the subject of intense debate [20,85].…”

“…Daptomycin resistance is rare globally, reflecting the fact that this drug is reserved as a last resort in humans, is rarely used in low-or middle-income settings and is not used for livestock [81,82]. However, daptomycin resistance can emerge during treatment, and reduced susceptibility is often seen in vancomycin-insensitive strains [83]. Daptomycin treatment is therefore more likely to fail when the causative organism is resistant to vancomycin [84].…”

Synergistic Effect of Cefazolin Plus Fosfomycin Against Staphylococcus aureus in vitro and in vivo in an Experimental Galleria mellonella Model

“…Daptomycin shows rapid bactericidal activity and is therefore a reliable alternative for severe MRSA infections ( Richter et al, 2003 ; Habib et al, 2015 ). However, it possesses some shortcomings, including a strong inoculum effect and notable rates of emergent resistance in patients with left-sided IE, highlighting the need for alternative regimens and rescue therapies ( Fowler et al, 2006 ; Moise et al, 2009 ; Morrisette et al, 2020 ). Due to its broad antimicrobial activity against Gram-positive and Gram-negative organisms, fosfomycin has been studied in combination with various beta-lactam antibiotics because of their wide therapeutic range and strong clinical efficacy.…”