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In vitro study of elution kinetics and biological activity of piperacillin/tazobactam and gentamicin in acrylic bone cement - 25/11/22

Doi : 10.1016/j.otsr.2022.103230 
Tarun Goyal a, , Puneet Dhamija b, Gyan Vardhan b, Pratima Gupta c, Vivek Trikha d
a Department of Orthopaedics, All India Institute of Medical Sciences, Dabwali Road, Bathinda, Punjab 151001, India 
b Pharmacology Department, All India Institute of Medical Sciences, Virbhadra Marg, Pashulok, Rishikesh, Uttarakhand 249203, India 
c Department of Microbiology All India Institute of Medical Sciences, Virbhadra Marg, Pashulok, Rishikesh, Uttarakhand 249203, India 
d Department of Orthopaedics, All India Institute of Medical Sciences, Virbhadra Marg, Pashulok, Rishikesh, Uttarakhand 249203, India 

Corresponding author.

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Abstract

Background

Antibiotics differ in their elution characteristics from bone cement. But no such data is available on piperacillin and tazobactam. Therefore, we performed an in vitro observational study to examine (1) in vitro elution characteristics of piperacillin and tazobactam from bone cement, (2) their biological activity using minimum inhibitory concentration and (3) elution characteristics and biological activity when combined with gentamicin in bone cement.

Hypothesis

The null hypothesis was that piperacillin and tazobactam after elution from bone cement can achieve concentrations higher than minimum inhibitory concentration.

Material and methods

Forty milligrams bone cement was mixed with the following combination of antibiotics: without any antibiotic (sample A, control), 4g/0.50g piperacillin/tazobactam (sample B), 6g/0.75g piperacillin/tazobactam (sample C), 8g/1.0g piperacillin/tazobactam (sample D) and 4g/0.50g piperacillin/tazobactam and 400mg gentamicin (sample E). Samples were analysed on reverse-phase ultra-high-performance liquid chromatography. Antibacterial activity in the elute were tested against standard American Type Culture Collection (ATCC) strains.

Results

Detectable drug elution for piperacillin and tazobactam was seen till 21days. Peak drug levels for all formulations were seen at 48hours (140.8 & 297.5μg/mL for samples B of piperacillin and tazobactam respectively). About 0.83–1.24% of piperacillin and 23.17–29.17% of tazobactam were released from the samples. Gentamicin improved elution of piperacillin and tazobactam: 140.8 vs. 919.9μg/mL (p=0.000) for samples B & E of piperacillin respectively and 297.5 & 1138.4μg/mL (p=0.001) for samples B & E of tazobactam respectively at 2days. Sample E showed complete inhibition of tested microorganisms, while B sample was microbiologically less active compared to E on day 5.

Conclusions

Piperacillin and tazobactam eluted successfully from bone cement and also retained antimicrobial activity after elution. Maximum elution was seen up to day 2 after which it reduced drastically. Antimicrobial action was seen up to 7days.

Level of evidence

III; comparative study.

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Keywords : Elution kinetics, Gentamicin, Bone cement, Piperacillin, Tazobactam, High pressure liquid chromatography


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Vol 108 - N° 8

Articolo 103230- dicembre 2022 Ritorno al numero
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