Antibiotics loaded beads for treatment of bone infection

Phase 1

Completed

• Conditions: Osteomyelitis and infected fractures and non-unions

• Registration Number: CTRI/2012/11/003143
• Lead Sponsor: Paediatric Orthopaedics Unit

Brief Summary

At present, inOrthopaedics, local administration of antibiotics in the region of infected andnecrotic bone and soft tissues is carried out by implanting preloaded PMMAbeads or freshly made loaded with antibiotics at the time of surgery. Clearly,antibiotic beads pose evidenced advantages over those systemicallyadministered. Studies have reported the former to produce negligible serumlevels, thereby avoiding systemic toxicity1,2,3. By eliminating theneed for iv use, it also decreases duration of hospitalization, patient comfortand overall treatment cost2,4. PMMA beads however have a limitationin it being non-biodegradable, thereby obviating the need for a second surgeryfor its extraction. The antibiotic release from PMMA beads is as low as 25% to50%5,6. This drawback has kicked development of biodegradable drugdelivery vehicles over the past few years.

The pharmacokinetic profile of hand rolledantibiotic beads is highly variable, due to its varying shape and surface area7.In vitro pharmacokinetic and *in vivo*animal studies have shown the bone concentrate levels above minimum inhibitoryconcentration for Vancomycin upto 28 days. *Invitro* studies with high concentrations of Gentamycin and Vancomycin haveshown to decrease osteoblastic activity and also cell death in very highconcentrations.

Inthis study highly porous hydroxyapatite (HAP) pellets are produced by a spray dryingand granulation method . The porosity in these material are in the range of 30nanometers. Normally , HAP bodies used for the orthopaedic and dentalapplication have larger pores in the micron scale. It has been found thatantibiotics can be loaded into these nanoporous material and hence can beapplied as a drug loaded bone filler for various dental and orthopaedicaplcations. Since HAP is fully degradable , removal is not required unlike PMMAbeads. Moreover The hydroxyapatite bead implantation is not associated withexothermic reaction hence it is unlikely that the drug will get inactivated bychemical or thermal reaction in the granules. Practically any antibiotic desiredaccording to sensitivity can be loaded into granules. In vitro studies done byDr Varma shows that significant amount of elution continues from the beads intotissue fluid occurs for 14 days.

**References:**

1. Adams K, Couch L, Cierny G, Calhoun J,Mader JT. In vitro and in vivo evaluation of antibiotic diffusion fromantibioticimpregnated polymethylmethacrylate beads.  Clin Orthop. 1992; 278:244-252

2. Blaha JD, Calhoun JH, Nelson CL, et al.Comparison of the clinical efï¬ cacy and tolerance of gentamicin PMMA beads onsurgical wire versus combined and systemic therapy for osteomyelitis. ClinOrthop. 1993; 295:8-12

3. PatzakisMJ, Mazur K, Wilkins J, Sherman R, Holtom P. Septopal beads and autogenous bonegrafting for bone defects in patients with chronic osteomyelitis.  Clin Orthop. 1993; 295:112-118.

4. Shih HN, Shih LY, Wong YC. Diagnosis andtreatment of subacute osteomyelitis.  JTrauma.2005; 58:83-87

5. Rushton N. Applications of localantibiotic therapy.  Eur J Surg Suppl.1997; 578:27-30.

6. Wilson KJ, Cierny G, Adams KR, Mader JT.Comparative evaluation of the diffusion of tobramycin and cefotaxime out ofantibiotic-impregnated polymethylmethacrylate beads.  J Orthop Res. 1988; 6:279-286.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-15
• Last Update Posted: 2015-04-07

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Children with pyogenic bone infections and infected non-unions.

Exclusion Criteria

Those who cannot be followed up for one year on a regular basis.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Major adverse effect such as allergic reactions	one year

Secondary Outcome Measures

Name	Time	Method
eradication of infection and improvement in bone healing	one year

Trial Locations

Locations (1)

Paediatric Orthopaedics Unit; 🇮🇳 Vellore, TAMIL NADU, India

Paediatric Orthopaedics Unit

🇮🇳Vellore, TAMIL NADU, India

Dr Vrisha Madhuri

Principal investigator

04162282171

madhuriwalter@cmcvellore.ac.in