Ge

Gentamicin

Clindamycin

Refobacin RevisionAntibiotic-loaded bone cement containing both gentamicin and clindamycin developed specifically for one- and two-stage revision surgeries, infections and high-risk patients

ClindamycinGentamicin

Clindamicin

Clindamycin

Gentamicin

Gentamicin

Refobacin Revision is a high viscosity, x-ray positive bone cement. It is a bone cement from Biomet, containing a combination of the two antibiotics gentamicin and clindamycin. This antibiotic combi-nation has the advantage of offering both a high local antibiotic concentration and a broad antibacterial spectrum. 40 gram Refobacin Revision contains 1 gram gentamicin and 1 gram clindamycin. The cement increases the available options for preventing infections and re-infections in total joint replacements.

Refobacin Revision is developed from Refobacin Bone Cement R specifically for one- and two-stage revision surgeries, infections and high-risk patients. Its combination of gentamicin and clindamycin is known to have an antibacterial effect on more than 90% of the bacteria common to infected arthroplasty cases.3

As all Biomet cements, Refobacin Revision contains chlorophyll, which gives the cement its characteristic green colour, for easy distinction from bone and body tissue during surgery.

In both the Norwegian Arthroplasty Register and in the Swedish Hip Arthroplasty Register the use of high viscosity cements with gentamicin has been shown to result in the lowest incidence of revision.4, 5 The reduced revision incidence in turn reduces the associated costs.5

1) Swedish Hip Arthroplasty Register, 20052) Malchau H, (2006) The infected hip a disaster, Lecture on cementing University Course, November

2-3, 2006, Malmo, Sweden3) Von Förster GV, Buchholz HW, Heinert K, (1988) Die infizierte Hüftendoprothese - Spätinfektion

nach der 6.post-operativen Woche. (The infected hip endoprosthesis-Late infection after 6th week postoperatively) In: Cotta H,Braun A (Hrgs).124-135.

4) Havelin L-I, Espehaug B, Lie S.A, Engesæter L.B, Furnes O, Vollset S.E, (2000) Prospective Studies of Hip Prostheses and Cements. A presentation of the Norwegian Arthroplasty Register 1987-1999. Scientific Exhibition presented at the 67th Annual Meeting of the American Academy of Orthopaedic Surgeons, March 15-19, 2000, Orlando, USA

5) Malchau H, Herberts P, Garellick G, Söderman P, Eisler T, (2002) The Prognosis of Total Hip Replacement, Scientific Exhibition presented at the 69th Annual Meeting of the American Academy of Orthopaedic Surgeons, February 13-17, 2002, Dallas, USA

Infection is a rare but serious complication after joint replacements. According to the Swedish Hip Arthroplasty Register approximately 8% of all revisions in Sweden are caused by infections.1

Infection is not only a serious complication that causes a lot of suffering for the patient. It is also costly since the cost for an infected hip is about 50 000 USD per surgery.2 A sound surgical and cementing technique decreases the risk of revisions. Antibiotic-loaded cement is an important element of the treatment of infected hip and knee joints.

Refobacin® RevisionBackground

2 | REFOBACIN® REVISION

Compressive strength

MP

aM

Pa

MP

a

100

80

60

40

20

0

Bending strength

ISO 5833

80

70

50

30

10

60

40

20

0

Young’s Modulus

3500

3000

2500

1500

500

2000

1000

0

ISO 5833

ISO 5833

REFOBACIN® REVISION | 3

“The cement increases the available options for preventing infections and re-infections in

total joint replacements”

HIGH QUALITY STANDARD

As the responsible manufacturer of Refobacin Revision, Biomet maintains a high quality standard. During production all raw materials have to fulfill demanding specific criteria. Refobacin Revision, as well as all other cements from Biomet undergo rigorous quality control under ISO 13485 and pharmaceutical standards, to guarantee a consistent high quality.

EXCELLENT MECHANICAL PROPERTIES

Bone cement is subjected to high mechanical stress. The mechanical properties of bone cement must therefore be tested for compressive strength, bending strength and Young’s modulus according to ISO 5833.6 Refobacin Revision exceeds the international standards established for strength (see illustrations).7

Control of quality and mechanical properties

Compressive strength

Bending strength

Young’s Modulus

Refobacin Revision exceeds the international standards established for strength

6) ISO 5833, Implants for Surgery -Acrylic Resin Cements (2002)7) Internal studies, Biomet Deutschland GmbH, Dieburg, Germany

4 | REFOBACIN® REVISION

Once settled, germs are less sensitive to antibiotics, rendering treatment with antibiotics ineffective. A solution to this problem is preventing the colonizing of germs. By using an antibiotic-loaded bone cement, high local concentrations of antibiotics can be administered, preventing exogen and endogen germs from colonizing. The protracted release of the antibiotics protects the implant for an extended period of time. While local antibiotic concentration is high in order to protect the implant, antibiotic levels in the serum and urine remain low, precluding side effects.

ANTIBIOTICS IN BONE CEMENT

Antibiotics added to bone cement must have the following characteristics:8, 9

• Broad coverage of the targeted bacterial spectrum

• Excellent release from bone cement

• Good thermal stability

• Resistance to sterilization

GENTAMICIN AND CLINDAMYCIN –OPTIMAL ANTIBIOTICS FOR BONE CEMENT

Gentamicin is bactericidal on proliferating and resisting pathogens and has proven to be the antibiotic of choice for bone cement. With its broad therapeutic spectrum, gentamicin covers a vide variety of gram-positive and gram-negative bacteria.10 The gentamicin has been specially treated by Merck KGaA according to a process proprietary to Biomet.

Clindamycin has a predominantly bacteriostatic effect on gram-positive bacteria such as staphylococci and streptococci as well as on gram-positive and gram-negative anaerobs. The combination of clindamycin and gentamicin is the most appropriate weapon in both one- and two-stage revisions because most pathogens causing periprosthetic infections have a susceptibility pattern covered by these agents.10

HIGH LOCAL ANTIBIOTIC CONCENTRATION

Antibiotic-loaded cements such as Refobacin Revision

Two antibiotics for increased efficiency

8) Kayser F. H. Novak J, Wüst J, (1983) Bacterial aspects of deep wound sepsis after total hip arthroplasty. In: Marti, R. K., (Ed), Progress in cemented total hip surgery and revision. Proceedings of a symposium, Amsterdam, October 16, 1982, Excerpta med, pp 7-17.

9) Steinbrink K, Frommelt L, (1995) Behandlung der periprothetischen Infektion der Hüfte durch einzeitige Austauschoperation. (Treatment of periprosthetic infection of the hip by a one-stage exchange operation). Orthopäde 24, 335-343.

10) Gehrke T, von Förster G, Frommelt L (2001) Pharmacokinetic study of a Gentamicin/Clindamycin Bone Cement Used in One-Stage Revision Arthroplasty; In: Bone Cements and Cementing Technique; Walenkamp, GHIM; Murray, DW (eds); Springer Verlag Berlin Heidelberg; pp 177-134

11) Lidgren L, (2001) Joint prosthetic infections: A success story, Acta Orthop Scand 72 (6): pp 553-556.

Antibiotic release from Refobacin Revision

Ant

ibio

tic r

elea

sed

(µg/

spec

imen

)

Days

100 1 2 3 4 5 6

100

1000

10000

Gentamicin

Clindamycin

REFOBACIN® REVISION | 5

provide effective concentrations of gentamicin and clindamycin in the tissue surrounding the implant. Additional clinical advantages of gentamicin- and clindamycin-loaded cements include low systematic and urinary antibiotic concentrations and a consequent lack of ototoxic and nephrotoxic complications.

GENTAMICIN-LOADED CEMENTS WITH PROVEN CLINICAL RESULTS

A considerable number of published case studies have confirmed the successful use of antibiotic-loaded

The combination of gentamicin and clindamycin is known to have an antibacterial effect on more than 90% of the bacteria common to infected cases.14

The Norwegian Arthroplasty Register shows that the combination of antibiotic-loaded cement and systemic antibiotics reduces the risk of revision more than any other regime.12

THR survival rates in Norway from 1987 to 1995

years

Sur

viva

l [%

]

p = 0.001no antibiotics

in cement onlysystemic onlysystemic and in cement

98,6

98,4

98,8

99,0

99,2

99,4

99,6

99,8

100

0 2 4 86

12) Espehaug B, Engesæter L. B, Vollset S. E, Havelin L. i, Langeland N, (1997) Antibiotic Prophylaxis in Total Hip Arthroplasty. Journal of Bone and Joint Surgery, Vol. 79 B, 590-595

13) Wahlig H, et al. (1987) Über die Freisetzung von Antibiotika aus Knochenzementen – Ergebnisse vergleichender Untersuchungen in vitro und in vivo. (Release of antibiotics from bone cements - Results of comparative tests in vitro and in vivo.) In: Knochenzement H.G Willert und G. Buchhorn (Eds.), Bern, 221-226.

14) Graph based on von Förster G.V, Buchholtz H.W, Heinert K, (1988) Die infi zierte Hüfendoprothese-Spätinfektion nach der 6. postoperativen Woche. (The infected hip endoprosthesis-Late infection after 6th week postoperatively). In: Knochen und Gelenkeninfektionen. Cotta H, Braun A (Eds) Springer Berlin. (Hrgs.) 124-135

In-vitro release of gentamicin and clindamycin from Refobacin Revision.7

cements.11, 12 Gentamicin-loaded cements in particular have shown good clinical results in both the Swedish Hip Arthroplasty Register and the Norwegian Arthroplasty Register.

LONG-LASTING LOCAL ANTIBIOTIC RELEASE

Both gentamicin- and clindamycin-loaded cements have a significantly higher in vitro release than most other antibiotics.13 These two antibiotics show similar elution properties with regard to both concentration and duration when mixed with bone cement in the same concentrations.10

6 | REFOBACIN® REVISION

ONE-STAGE REVISION

Although the results of primary total hip and knee arthroplasties generally are excellent, some failures do occur over time.15 During one-stage revision surgery, the implant, the former cement mantle and all foreign material are removed. After a thorough lavage, and in some cases bone impaction, the prosthesis components are fixed with an antibiotic-loaded cement.

TWO-STAGE REVISION

In a two-stage revision, a patient matched temporary spacer made of antibiotic-loaded cement such as Refobacin Revision may be used. This temporary cement spacer prevents bone-on-bone contact and contraction of soft tissue and also stabilizes the infected joint. The non weight-bearing spacer remains in place until the infection has been successfully treated, normally 6-8 weeks. It is then removed and replaced with a conventional joint prosthesis.

One- and two-stage revisions Easy handling

Application of non-prechilled Refobacin Revision mixed under vacuumI: mixing phase III: application phase II: waiting phase IV: final hardening phase

15) Petty W, (1991) Total Joint Replacement, WB Saunders company, Philadelphia, USA

For mixing and delivery of Refobacin Revision it is recommended to use a closed vacuum mixing system, such as Biomet’s Optivac®.

This ensures a reproducible, homogeneous bone cement of high quality. Handling properties are very dependent on the temperature of the bone cement and operating room. Higher temperature results in shorter working phase and faster setting time. If the cement is pre-chilled both the working phase and the setting time are prolonged.

PATIENT MATCHED CEMENT

Biomet’s standard range of bone cement covers most cases when cemented arthroplasty is necessary. Some times however, these cements are not adequate. In such cases, Biomet can offer a patient matched bone cement manufactured acc-ording to the European Medical Device Directive.* Patient matched bone cement is made specially for a certain patient and the main indication is MRSA. * Patient matched bone cements are produced upon request from the surgeon, using the patients antibiogram.

REFOBACIN® REVISION | 7

Biomet offers various sizes of spacer molds for the knee and hip. These molds can be used to produce temporary cement spacers for infected joints. For these applications an appropriate antibiotic-loaded cement should be used.

The joint spacer molds are sterile disposables made of medical grade silicone. They can be filled with bone cement by injection with a cement delivery gun. After the cement has cured, the temporary spacer is removed from the mold and the joint spacer is now ready for use.

Handling spacer molds

1. 2.

3.

4.

1. 2. 4.

Fill the stem of the mold first.

3.

Fill the tibial mold by injecting cement into its open top.

Continue the filling of cement into the head.

Fill the femoral mold by in-ject ing in the delivery port.

Once the cement is cured, press thumbs into the depression on the bottom of the mold foot and peel the mold away from the hip spacer. Trim the hip spacer if necessary.

When cured, remove the spacer from the mold.

Ready spacer and its mold.

Ready spacers and their molds.

Hip

Knee

Detailed instructions on how to use Biomet’s spacer molds are found in the instructions for use included in the package.

Refobacin Revisionwith gentamicin and clindamycin

3011630001

1 x 40

1 sachet of 42.9 g powder 1 ampoule of 20 ml liquid

Ordering information

Hip Cement Spacer MoldsCollarless bi-metric style stem with an endo style head

Catalog no. Stem Size Head Size Recommended Number (mm) (mm) Cement Single Mixes

431107 9 x 125 43 2 431109 9 x 125 51 3 431113 13 x 145 57 4 431117 17 x 165 64 5

Knee Cement Spacer MoldsCruciate sacrificing universal AGC style components

Catalog no. Femoral Mold Size Recommended Number (mm) Cement Single Mixes

432160 60 2 432165 65 2 432170 70 2 432175 75 2

Catalog no. Tibial Mold Size Recommended Number (mm) Cement Single Mixes

433165 65 2 433170 70 2 433175 75 2 433180 80 2

• Prevents bone-on-bone contact and soft tissue contraction

• Stabilizes infected joints

• Various sizes for both hip and knee

• Aids joint mobility and function recovery

• Accommodates protracted antibiotic release

For further inquires please contact:Biomet Cementing TechnologiesBox 306, 201 23 Malmö, SwedenPhone + 46 40 669 7000www.bonecement.comse.bonecement@biomet.com

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Biomet Bone Cements – a complete range

Spacermolds: US Patents 6,155,812 and 6,361731, European patent pending

Responsible manufacturer Spacer MoldsBiomet Orthopaedics Inc56 East Bell DriveP.O BOX 587Warsaw IN 46581, USA

Responsible manufacturer Refobacin RevisionBiomet Orthopaedics Switzerland GmbHCH-8953 DietikonSwitzerland

Endorsed by Dr. Thorsten Gehrke, Endo-klinik, Hamburg

Refobacin Revision is a bone cement from Biomet, containing a combination of the two antibiotics gentamicin and clindamycin, tailor-made for revision surgeries. Refobacin Revision is however only a small part of Biomet’s complete bone cement range, which also includes:

ANTIBIOTIC LOADED CEMENTS

• RefobacinBoneCementR• RefobacinPlusBoneCement

PLAIN CEMENTS

• BiometBoneCementR• BiometPlusBoneCement

SPECIALITY CEMENTS

• BiometBoneCementV• BiometBoneCementLV