Addition of ceftaroline fosamil or vancomycin to PMMA: An in vitro comparison of biomechanical properties and anti-MRSA efficacy

Abstract

Background: Ceftaroline is a cephalosporin that is effective against methicillin-resistant Staphylococcus aureus (MRSA) infections. The objective of this study was to determine the feasibility of using ceftaroline-loaded Polymethyl methacrylate (PMMA) as antibiotic cement against MRSA versus vancomycin-loaded PMMA in an in vitro setting. Methods: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay. Results: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 + 0.51 N (p < 0.001) and axial loading was 41.95 N + 0.51 (p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 + 0.79 N (p ¼ 0.02) and axial loading was 49.49 + 2.21 N (p ¼ 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 + 0.1 mg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 + 0.0 mg/ml. Conclusions: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.

Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus

“…It was found that the resistance mechanism of vancomycin is mainly specific binding of vancomycinto the bacterial cell wall via peptidoglycan precursor small peptides, which are terminated with D-alanyl-D-alanine; this binding inhibits the elongation and cross-linking of bacterial cell wall peptidoglycans, thereby repressing cell wall synthesis and ultimately leading to bacterial death (Micek, 2007;Haseeb et al, 2019). However, the resistance of Staphylococcus aureus to vancomycin is increasing daily, causing widespread concern in the medical community (Haseeb et al, 2019 (Amberpet et al, 2019). VRSA refers to a minimal inhibitory concentration (MIC) of clinically isolated Staphylococcus aureus to vancomycin <32 mg/L, and was first reported in the United States in 2002.…”

“…These virulence factors are chiefly exotoxins that disrupt host cells, interfere with immune responses, and some proteins involved in adhesion and defense against host defenses (Kalia and Purohit, 2011;Yin et al, 2011). The expression of virulence factors is regulated by a complex network composed of multiple genes, of which agr a global regulatory factor H1, is the most important gene regulated by quorum sensing mechanisms (Haseeb et al, 2019). However, the inhibition of this quorum sensing mechanism in bacteria could result in the obstruction of biofilm formation, reduction in bacterial virulence and decreased bacterial resistance (Wang et al, 2017;Haseeb et al, 2019).…”

Multi-site infection by methicillin-resistant Staphylococcus aureus in a six-year old girl: a case report

“…MRSA is not only resistant to β-lactam antibiotics, but also to other antimicrobial agents such as aminoglycosides, quinolones, and macrolides, and vancomycin has long been considered the first-line antibiotic treatment for invasive MRSA infection, including both HA-MRSA and CA-MRSA [ 18 ]. However the use of vancomycin has many shortcomings such as the slow bactericidal activity, high minimum inhibitory concentrations (MICs), reduced activity against biofilm-forming pathogens, and poor tissue penetration [ 19 ]. Several researchers [ 18 , 20 ] have shown that a subtherapeutic trough level of vancomycin is the main cause of treatment failure.…”

Multi-Site Infections Caused by Methicillin-Resistant Staphylococcus Aureus in a Six-Year Old Girl: A Rare Case Report

“…Vancomycin has long been considered the rst-line antibiotic treatment for invasive MRSA infection, including both HA-MRSA and CA-MRSA. However the use of vancomycin is limited because of its shortcomings such as the slow bactericidal activity, increased minimum inhibitory concentrations (MICs), reduced activity against bio lm-forming pathogens, and poor tissue penetration [22]. Several researchers have shown that subtherapeutic trough vancomycin concentration is the main reason of treatment failure.…”