Targeted Therapy of Severe Infections Caused by Staphylococcus aureus in Critically Ill Adult Patients: A Multidisciplinary Proposal of Therapeutic Algorithms Based on Real-World Evidence

Abstract

(1) Introduction: To develop evidence-based algorithms for targeted antibiotic therapy of infections caused by Staphylococcus aureus in critically ill adult patients. (2) Methods: A multidisciplinary team of four experts had several rounds of assessment for developing algorithms concerning targeted antimicrobial therapy of severe infections caused by Staphylococcus aureus in critically ill patients. The literature search was performed by a researcher on PubMed-MEDLINE (until August 2022) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Two different algorithms were created, one for methicillin-susceptible Staphylococcus aureus (MSSA) and the other for methicillin-resistant Staphylococcus aureus (MRSA). The therapeutic options were categorized for each different site of infection and were selected also on the basis of pharmacokinetic/pharmacodynamic features. (3) Results: Cefazolin or oxacillin were the agents proposed for all of the different types of severe MSSA infections. The proposed targeted therapies for severe MRSA infections were different according to the infection site: daptomycin plus fosfomycin or ceftaroline or ceftobiprole for bloodstream infections, infective endocarditis, and/or infections associated with intracardiac/intravascular devices; ceftaroline or ceftobiprole for community-acquired pneumonia; linezolid alone or plus fosfomycin for infection-related ventilator-associated complications or for central nervous system infections; daptomycin alone or plus clindamycin for necrotizing skin and soft tissue infections. (4) Conclusions: We are confident that targeted therapies based on scientific evidence and optimization of the pharmacokinetic/pharmacodynamic features of antibiotic monotherapy or combo therapy may represent valuable strategies for treating MSSA and MRSA infections.

Antibiotic Resistance to Molecules Commonly Prescribed for the Treatment of Antibiotic-Resistant Gram-Positive Pathogens: What Is Relevant for the Clinician?

“…However, it is possible to assert that the use of daptomycin in combination can be considered as standard of care in the context of IE (regardless of the species involved) [21] and in the treatment of viridans streptococci, since in these cases the risk of the emergence of resistance is sufficiently concrete. In other circumstances, combination therapy should be taken into consideration in case of difficult-to-treat infections [15,21,[50][51][52]57].…”

“…As already underlined, ceftaroline has been studied in combination with other anti-MRSA antibiotics (particularly daptomycin) for the treatment of BSI, including IE. This association has been proposed in order to increase the anti-bacterial efficacy and protect daptomycin from the emergence of resistance during treatment [15,21,51,52,57].…”

“…Another promising association is fosfomycin plus linezolid for the rescue therapy of severe VAP and CNS infections. These combinations may provide a synergistic antibacterial activity and reduce the risk of the emergence of resistance [15,19,146].…”

“…The most relevant of these are daptomycin [8], dalbavancin [9], linezolid [10], tedizolid [11], ceftaroline [12], ceftobiprole [13], and fosfomycin [14]. The availability of these drugs allowed clinicians to limit the use of vancomycin, which is burdened by greater adverse effects and lower efficacy [15].…”