Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement

Abstract

ObjectivesThermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.MethodsIn this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.ResultsThe heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions.ConclusionsThis study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers.Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.

Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm

“…Fang et al heated metal implants in a rat model to 75 C without any significant thermal damage to the surrounding tissue [31]. These studies are in agreement with Samara et al, who have shown that bone cement achieves durable fixation despite the temperature reaching 80 C for more than 10 min, caused by the curing process of the cement [14]. Furthermore special heating techniques such as segmental induction heating can be used to apply localized heating to a segment of an implant using the remainder of the implant as a heat sink and to avoid damage to vital areas of the implant necessary to maintain fixation [10].…”

“…There may be concerns for thermal necrosis when heating metal implants to 60-80 C. However, such temperatures are not uncommon in orthopedic surgery with cementing, drilling and using diathermia [11][12][13]. For instance, Samara et al have shown that bone cement, which achieves durable fixation for e.g., hip and knee implants reaches temperatures of 80 C for more than 10 min during the curing process [14]. Additionally, special heating techniques such as segmental induction heating can be used to apply localized heating to a segment of an implant, using the remainder of the implant as a heat sink [10].…”

Progress of antibiotic-loaded bone cement in joint arthroplasty

“…Thermogenesis of polymerization: The polymerization of PMMA is an exothermic reaction, [ 36 ] and thus, it is believed that only “heat-stable” antibiotics could tolerate the partial high temperature caused by polymerization. An in vitro test for 38 frequently used antibiotic agents found aminoglycoside, glycopeptide, tetracycline, and quinolone as “heat-stable” and β-lactam as “heat-sensitive.” [ 37 ] Carli et al [ 38 ] conducted thorough research in this field. They measured temperatures of PMMA cured inside silicone molds of the distal femur and proximal tibia and then incubated vancomycin (representing “heat-stable”) and ceftazidime (representing “heat-sensitive”) in accordance with the temperature curves collected from molds.…”

In vitro study of new combinations for local antibiotic therapy with calcium sulphate - Near constant release of ceftriaxone offers new treatment options

“…However, PMMA is not resorbable, implying the disadvantages of incomplete drug release and requirement of secondary removal 2 , 5 - 7 . For many practical and historical reasons, the antibiotics added to PMMA are mostly limited to glycopeptides, such as vancomycin and teicoplanin, aminoglycosides, such as gentamicin or tobramycin, or clindamycin 1 , 4 , 5 , 8 .…”