In vitro study of elution kinetics and bio-activity of meropenem-loaded acrylic bone cement

Abstract

BackgroundUse of antibiotic-loaded acrylic bone cement to treat orthopaedic infections continues to remain popular, but resistance to routinely used antibiotics has led to the search for alternative, more effective antibiotics. We studied, in vitro, the elution kinetics and bio-activity of different concentrations of meropenem-loaded acrylic bone cement.MethodsMeropenem-loaded bone cement cylinders of different concentrations were serially immersed in normal saline. Elution kinetics was studied by measuring the drug concentration in the eluate, collected at pre-determined intervals, by high-performance liquid chromatography. Bio-activity of the eluate of two different antibiotic concentrations was tested for a period of 3 weeks against each of the following organisms: Staphylococcus aureus ATCC 2593 (MSSA), Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, S. aureus ATCC 43300 (MRSA) and Klebsiella pneumoniae ATCC 700603 (ESBL).ResultsMeropenem elutes from acrylic bone cement for a period of 3–27 days depending on the concentration of antibiotic. Higher doses of antibiotic concentration resulted in greater elution of the antibiotic. The eluate was found to be biologically active against S. aureus ATCC 2593 (MSSA), P. aeruginosa ATCC 27853, E. coli ATCC 25922 and K. pneumoniae ATCC 700603 (ESBL) for a period of 3 weeks.ConclusionsThe elution of meropenem is in keeping with typical antibiotic-loaded acrylic bone cement elution characteristics. The use of high-dose meropenem-loaded acrylic bone cement seems to be an attractive option for treatment of resistant Gram-negative orthopaedic infections but needs to be tested in vivo.

Antibacterial effect of acrylic bone cements loaded with drugs of different action’s mechanism

“…The strategies to face up this new and complex context include the use of novel antimicrobial agents with high bone penetration for oral and parenteral antibiotic treatment such as: linezolid, daptomycin and tigecycline [22]; the exploration of the use of nonclassical antibiotics to load acrylic bone cement such as: amphotericin B [23], grepafloxacin [24], teicoplanin [25] or meropenem [26]; the use of combined drugs in the cements in order to increase the antimicrobial spectrum and the potential antibiotics concentrations in tissues as gentamicin/linezolid [27], vancomycin/linezolid [27], gentamicin/teicoplanin [28], vancomycin/daptomycin [29], vancomycin/cefazolin [30], ciprofloxacin/ceftazidime [31], ciprofloxacin/meropenem [31] or the development of biodegradable implants for local antibiotics release in Osteomyelitis therapy [32].…”

Osteomyelitis: an overview of antimicrobial therapy

“…Its use results in a lower serum antibiotic concentration than that associated with systemic administration, thereby reducing toxicity-related side-effects (Joosten et al, 2005;Samuel et al, 2012) (Table II).…”

“…Nevertheless, taking into account the numerous recently published in vitro and in vivo studies related to antibiotic loaded PMMA systems (Marra et al, 2001;Efstathopoulos et al, 2008;Samuel et al, 2012), it is expected they will remain in the near future an effective drug delivery system for local antibiotic therapy in osteomyelitis.…”

“…Efstathopoulos et al (2008) evaluated the efficacy of grepafloxacin loaded acrylic bone cement (polymethylmethacrylate, PMMA) for the treatment of experimentally chronic osteomyelitis induced in rabbits. Just recently, Samuel et al (2012) evaluated the bioactivity of meropenem loaded bone cement with possible application in Gram negative bone infections. Presently, the major concern related to the use of PMMA-based local antibiotic delivery system refers to the risk of induction of antibiotic resistance due to their possible contribution to enhancing biofilm formation on the material and selecting resistant mutants (Campoccia et al, 2010).…”

In vitro efficacy of antibiotic beads in treating abdominal vascular graft infections

“…The elution of meropenem from PMMA has been shown to be effective for up to 3 weeks. 15 The combination of meropenem and daptomycin provides broad-spectrum antimicrobial coverage.…”