Beta-lactam combination therapy for the treatment of Staphylococcus aureus and Enterococcus species bacteremia: A summary and appraisal of the evidence

Abstract

Staphylococcal bacteremia and enterococcal bacteremia are prevalent in hospitalized or recently instrumented patients, and are associated with significant morbidity and mortality. They are often difficult to treat due to the pathogenicity of the organisms, poor response to antibiotics, and increasing development of multidrug resistance. Therefore, there has been increasing interest in combination therapy for the treatment of these infections. The aim of this review was to summarize and assess the evidence supporting combination beta-lactam therapy for both Staphylococcus aureus and Enterococcus species blood stream infections. Currently, there is promising in vitro data but little clinical evidence supporting combination beta-lactam therapy for this indication. Further clinical investigations are needed to elucidate the potential benefits of beta-lactam combination therapy over monotherapy for Gram-positive bacteremia, although combination therapy may be useful in refractory cases of bacteremia that do not respond to standard antibiotic therapy.

Assessment of Susceptibility to Five Common Antibiotics and Their Resistance Pattern in Clinical Enterococcus Isolates

“…Combination antibiotic therapy can be a significant strategy for treating infections caused by Enterococcus species. Data showing that this strategy can lead to improved rates of cure and lower rates of relapse when compared to monotherapy (5,18). Currently, combination therapy of a cell wall-active agent such as vancomycin, teicoplanin, and fosfomycin trometamol plus an aminoglycoside like gentamycin and quinupristin/dalfopristin is as a standard protocol for treatment of enterococcal infections (44).…”

“…The most common human infectious strains of Enterococcus are E. faecalis (85-90%) and E. faecium (10-15%) leading to urinary tract infections, endocarditis, bacteremia, wound infection, abdominal infections, pelvic infections, and meningitis (4). On the other hand, about 30% of all nosocomial bloodstream infections are associated with Enterococcus species and Staphylococcus aureus, resulting in significant morbidity and mortality (5)(6)(7)(8). Based on the United States Nosocomial Infections Surveillance System's data, Enterococci are considered as one of the nosocomial pathogens (9).…”

“…Enterococcal tolerance to these antibiotics can be affected by combining cell-wall active agents with an aminoglycoside based on synergistic bactericidal activity. Studies have shown that a higher concentration of aminoglycoside enters cells that are also treated with agents that inhibit cell wall synthesis, which suggests that the cell wall active agents promote uptake of the aminoglycoside (5,14). Accordingly, to treat infections caused by Enterococci, combination therapy with a cell wall-active agent and a synergistic aminoglycoside should be considered.…”

Cell Membrane Damage of Prokaryotes and Analysis of the Cell Death Type in Eukaryotes by Fluorescence Microscopy

“…Antibiotics act inhibiting the synthesis of the cell wall composed of peptideoglycan. Inhibiting bacterial growth and causing death, as example have beta-lactams, vancomycin (Bartash and Nori, 2017) and bacitracin. Betalactams inhibit cross-linking of the cell wall, vancomycin interferes with the addition of new subunits in the cell wall (murine pentapeptide), and finally, bacitracin prevents the addition of cell wall subunits by inhibiting recycling of the membrane lipid carrier.…”

Antibacterial effects of vancomycin in combination with methicillin against methicillin-resistant and methicillinsensitive Staphylococcus aureus

“…Recent investigations in antibacterial development encompass using the combination therapy with two or more antibacterial compounds. However, several combined therapies with vancomycin are reported (13)(14)(15)(16)(17)(18) as well. So far, a limited body of data has published regarding the efficacy of vancomycin in combination with methicillin on genes contributing to the antibacterial resistance of S. aureus.…”