Increased release of gentamicin from acrylic bone cements under influence of low-frequency ultrasound

Hendriks, Johannes G.E.; Ensing, G.T.; Horn, J.R. van; Lubbers, Jaap; Mei, Henny C. van der; Busscher, Henk J.

doi:10.1016/s0168-3659(03)00361-4

Cited by 28 publications

(51 citation statements)

References 29 publications

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“…However, it is sometimes deficient in antimicrobial efficacy (21). Many authors have attributed this defect to the incomplete release of the antibiotic from the cement (4,5,6,8,20,23,24). The matrix of polymethylmethacrylate is, to a large extent, impermeable to antibiotics.…”

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confidence: 99%

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Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

Cai

Yan

et al. 2007

Antimicrob Agents Chemother

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This study sought to investigate the effect of delayed pulsed-wave ultrasound with low frequency on drug release from and the antimicrobial efficacy of vancomycin-loaded acrylic bone cement in vivo and the possible mechanism of this effect. After the implantation of cement and the inoculation of Staphylococcus aureus into the bilateral hips of rabbits, ultrasound (average intensity, 300 mW/cm 2 ; frequency, 46.5 kHz; on/off ratio, 20 min/10 min) was applied to animals in the normal ultrasound group (UG 0-12 ) from 0 through 12 h after surgery and to those in the delayed-ultrasound group (UG 12-24 ) from 12 through 24 h after surgery. The control group (CG) was not exposed to ultrasound. Based on vancomycin concentrations in left hip cavities at projected time intervals, the amount of time during which the local drug concentration exceeded the MIC (T >MIC ) in UG 12-24 was significantly prolonged compared with that in either CG or UG 0-12 , and the ratios between the areas under the concentration-time curves over 24 h and the MIC for UG 0-12 and UG 12-24 were both increased compared with that for CG. The greatest reductions in bacterial densities in both right hip aspirates and right femoral tissues at 48 h were achieved with UG 12-24 . Local hemorrhage in rabbits of UG 0-12 during the 12-h insonation was more severe than that in rabbits of UG 12-24 . Of four variables, the T >MIC and the bioacoustic effect were both identified as parameters predictive of the enhancement of the antimicrobial efficacy of cement by ultrasound. Sustained concentrations above the MIC replaced early high maximum concentrations and long-term subtherapeutic release of the drug, provided that ultrasound was not applied until local hemorrhage was relieved. The enhancement of the antimicrobial efficacy of cement by ultrasound may be attributed to the prolonged T >MIC and the bioacoustic effect caused by ultrasound.Of the patients worldwide undergoing total joint replacement per year, approximately 0.3 to 2.2% develop prosthesis-related infections resulting in devastating surgical failure (23,25). Antibiotic-loaded bone cement is the treatment of choice because of its high local dose and low systemic toxicity compared with those of intravenous antibiotics (23,25). However, it is sometimes deficient in antimicrobial efficacy (21). Many authors have attributed this defect to the incomplete release of the antibiotic from the cement (4,5,6,8,20,23,24). The matrix of polymethylmethacrylate is, to a large extent, impermeable to antibiotics. Not only is the bioavailability of the antibiotic decreased, but the prolonged exposure to the antibiotic also allows selective bacterial resistance to occur (20).Recently, low-frequency ultrasound has been found to enhance the release of gentamicin from cement (4, 8). Two possible mechanisms behind this phenomenon include acoustic streaming and an accelerated rate of mass transfer as a result of stable cavitation and the ultrasonic pressure wave. Also, such enhanced release of gentamicin may contribute to a d...

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confidence: 99%

“…Recently, low-frequency ultrasound has been found to enhance the release of gentamicin from cement (4,8). Two possible mechanisms behind this phenomenon include acoustic streaming and an accelerated rate of mass transfer as a result of stable cavitation and the ultrasonic pressure wave.…”

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confidence: 99%

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

Cai

Yan

et al. 2007

Antimicrob Agents Chemother

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“…This technique is only effective if the dissolution fluids can penetrate the polymer matrix to release the antibiotics and more often than not the drug remains embedded in the cement. The control of the drug release is extremely dependant on the porosity of the polymer and release rates are generally low and ineffective 19 . Belt et al, 20 studied the gentamicin released from six different commercial PMMA bone cements.…”

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confidence: 99%

Characteristics, interactions and coating adherence of heterogeneous polymer/drug coatings for biomedical devices

McManamon

Silva

Delaney

et al. 2016

Materials Science and Engineering: C

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“…Previous antimicrobial exposure has been reported to have a negative effect on microbiologic diagnosis (4,5). Moreover, it has been shown that in vitro application of pulsed ultrasound leads to increased release of gentamicin from antimicrobial-loaded bone cement (6). Therefore, the aim of this study was to determine, by using a retrospective review of clinical cases, whether antimicrobial-loaded PMMA influences sonicate fluid culture positivity.…”

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confidence: 99%

“…We applied ultrasound to dislodge adherent bacteria. It has been found that in vitro application of pulsed ultrasound (46.5 kHz and 167 mW/ cm 2 ) can lead to an increase in the release of antimicrobials from antimicrobial-loaded cement or beads (6,11), and low-frequency pulsed ultrasound (300 or 600 mW/cm 2 ) has been found to result in an increase in the activity of antimicrobials against biofilm bacteria (the bioacoustic effect) (12), suggesting that antimicrobial-loaded PMMA could negatively impact sonicate culture results. The results of our study show that antimicrobial-loaded PMMA does not have an obvious negative impact on the microbiologic yield from explanted prostheses when sonication is used.…”

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Antimicrobial-Loaded Bone Cement Does Not Negatively Influence Sonicate Fluid Culture Positivity for Diagnosis of Prosthetic Joint Infection

et al. 2016

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We compared culture results to investigate the influence of antimicrobial-loaded cement on sonicate fluid culture positivity for the diagnosis of prosthetic joint infection. Fifty-four subjects were assessed. The sensitivities of sonicate fluid culture were 77.8% (14 of 18) in subjects with an antimicrobial-loaded cemented prosthesis and 58.3% (21 of 36) in subjects with an antimicrobialfree prosthesis. With the increasing number of lower-extremity total joint arthroplasty surgeries, there has been an increase in the number of prosthetic joint infections (PJIs) (1). Organisms associated with PJI attach to the implant, polymethylmethacrylate (PMMA), and/or bone surfaces, where they grow in biofilms. Antimicrobialloaded PMMA is used in the prevention and treatment of PJI (2, 3). We previously reported that culture of fluid obtained by sonication of removed implants is more sensitive than culture of conventional periprosthetic tissue for the diagnosis of PJI (4). Previous antimicrobial exposure has been reported to have a negative effect on microbiologic diagnosis (4, 5). Moreover, it has been shown that in vitro application of pulsed ultrasound leads to increased release of gentamicin from antimicrobial-loaded bone cement (6). Therefore, the aim of this study was to determine, by using a retrospective review of clinical cases, whether antimicrobial-loaded PMMA influences sonicate fluid culture positivity.PJI was diagnosed using Infectious Diseases Society of America guidelines if at least one of the following was present: a sinus tract communicating with the prosthesis, purulence noted at the time of surgery, or acute inflammation detected on intraoperative frozen section histology (7). Patients with removal of spacers during the two-stage exchange process or subjects who were Ͻ18 years old as well as those with the criteria noted below were excluded. Between April 2006 and August 2015, 362 patients with confirmed PJI undergoing removal of a total knee or hip prosthesis at Mayo Clinic, Rochester, Minnesota, were enrolled; 227 were excluded because they had received antimicrobial therapy within 4 weeks before the collection of the implant for culture, 80 were excluded because of insufficient medical record information, and one who had a Mycobacterium chelonae infection was excluded. A total of 54 patients were enrolled, and all had undergone removal of a single prosthesis.Tissue culture was performed on 2 to 7 periprosthetic tissue specimens per patient. Implants were cultured according to a previously described protocol, which included sonication, vortexing, and concentration (8). Briefly, the container was vortexed for 30 s and subjected to sonication (40 kHz and 320 mW/cm 2 for 5 min). Sonicate fluid culture positivity was determined according to a previously described method (8). The Mann-Whitney U test was used to compare the continuous variables, and the 2 test was used to compare the categorical variables. All P values were two tailed, and a P value of Ͻ0.05 was considered statistically significant. The sens...

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Increased release of gentamicin from acrylic bone cements under influence of low-frequency ultrasound

Cited by 28 publications

References 29 publications

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

Characteristics, interactions and coating adherence of heterogeneous polymer/drug coatings for biomedical devices

Antimicrobial-Loaded Bone Cement Does Not Negatively Influence Sonicate Fluid Culture Positivity for Diagnosis of Prosthetic Joint Infection

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