Dosing Considerations for Combination Antistaphylococcal β-Lactam and Glyco/lipopeptide Salvage Therapy for Resistant Gram-Positive Infections: A Systematic Review

Abstract

Objective:

The objective of this systematic review is to evaluate dosing regimens of combination salvage regimens used as part of infectious disease pharmacotherapy.

Data Sources:

A systematic review was conducted on PubMed, MEDLINE, Scopus, ProQuest Central, and CINAHL through March 2021 using the following terminology: “combination” OR “Seesaw” OR “see-saw” OR “salvage” AND “infection” OR “resistant infection” OR “Gram-positive” AND “beta-lactam” OR “cephalosporin” OR “carbapenem” OR “monobactam” OR “glycopeptide” OR “lipopeptide.”

Study Selection and Data Extraction:

Following the application of inclusion and exclusion criteria, 8 pieces of literature were ultimately included in this review.

Data Synthesis:

Vancomycin in combination with another agent was most commonly prescribed as initial or empirical therapy. The most common combination salvage therapy regimen consisted of daptomycin in doses up to 12 mg/kg IV every 24 hours with ceftaroline 200 to 600 mg IV every 8 to 12 hours. Although the duration of combination salvage therapy varied drastically, blood culture clearance was typically observed within 24 hours.

Relevance to Patient Care and Clinical Practice:

Antimicrobial-resistant Gram-positive organisms have posed an emergent threat to antimicrobial stewardship initiatives. Utilizing either a glycopeptide or lipopeptide antibiotic in combination with an antistaphylococcal β-lactam antibiotic has demonstrated efficacy in treating resistant bacteria. This work describes the heterogeneity of dosing regimens and seeks to define an optimal dose, duration, and combination of antibiotics.

Conclusions:

Combination salvage therapy has demonstrated efficacy and safety in treatment of resistant Gram-positive infections. It appears the combination of daptomycin and ceftaroline can clear resistant infections expeditiously.