日小整会誌（J Jpn Ped Orthop Ass）23（2）：433 440, 2014.
第 24 回日本小児整形外科学会学術集会 JPOA Asian Fellows

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local
Antibiotic Delivery System in Controlled Osteoarticular Infection
Lakhwani OP, Associate Professor Orthopaedics Surgery；
Kapoor S K, Professor Orthopaedics surgery and Dean
ESIC- Post Graduate Institute of Medical Sciences and Research
ESI Hospital, Basaidarapur, Ring road, New Delhi, India

Abstract：【Introduction】Osteomyelitis is dreaded infection necessitating prolonged and sustained antibiotic therapy which carries the disadvantages of systemic adverse eﬀects and highcost of therapy. Current study aims to assess safety and eﬃcacy of use antibiotic loaded allogenic
cancellous bone as a carrier of antibiotics in controlled osteoarticular infection.
【Materials and Methods】
Study involved case series of twelve patients with localized and controlled osteoarticular infection. Hydrophilic antibiotics were selected according to common organism responsible for the osteoarticular infection and culture and sensitivity. Allogenic cancellous
antibiotics impregnated bone graft augmented with autologous bone graft or Bone marrow aspirate was used along with appropriate surgical procedure.
【Results】
Patients were evaluated for infection eradication and osteointegration. Over all 6 cases were treated successfully thus obviating any subsequent procedure. Infection was eradicatedin 10 cases. Osteointegration was achieved in all the cases in which autologous bone graft wasused as adjuvant and in two out of four cases in which bone marrow aspirate was also used）.
Two cases were considered failure which required secondary procedures and change of ﬁxation.
【Conclusion】
Cancellous bone allograft as antibiotic carrier clinically provided safe, prolong andeﬀective local antibiotic for treating osteoarticular Infection. It may be superior to surgical debridement and systemic antibiotic alone for infection eradication and may oﬀer better osteointegration when used along with adjuvants like autologous bone graft or Bone marrow.
【Level of Evidence】level IV. Study can serve clinical basis of using the allogenic bone graft as
carrier of antibiotics for safe and cost beneﬁcial treatment of osteoarticular infection avoiding
side eﬀects of systemic antibiotics and simultaneously aiding bone healing by osteointregation.

INTRODUCTION
Bone and joint infections are known for chro-

nicity, diﬃcult eradication and osteolysis require
prolonged systemic antibiotics for treatment.
Surgical debridement alone may be ineffective

Key words：allogenic bone graft, local antibiotic, osteomyelitis
Correspondence duther：Dr. O P Lakhwani
Associate Professor Department of Orthopaedics Surgery
ESI Hospital, ESI PGIMSR
Basaidarapur, Ring road, New Delhi‒110015, India.
E-mail ‒ orth365@gmail.com, dr.omprakash.lakhwani@esic.in
Phone :＋91 9555628578, Fax :＋91 11‒25440722
日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

in eliminating micro-clusters from biofilms and
3）

The inclusion criteria were patients of all age

small colony variant bacteria that survive andgroup with localized and controlled osteoarticu-

replicate intracellularly in osteoblast, mac-

lar infection（in whom adequate surgical margins

rophages and other cells leading to recurrence

free from dead necrotic tissue could be achieved

2）

of infection . These pathogens are also diﬃcult

after surgical debridement）
and wound coverage

to retrieve and missed in culture. Hence high lo-

could be obtained primarily by suturing or ﬂap

cal concentration of antibiotic for a prolonged

coverage. Patient having minimum followup of

duration is desirable to eliminate such patho-

six months were included in the study. Exclu-

gens.

sion criteria were active osteoarticular infection

Antibiotics loaded synthetic material

5）6）

like

and hypersensitivity to the antibiotics to be

Poly methyl metha acrylate bone cement

used in the study. Hydrophilic antibiotics among（PMMA）, Calcium hydroxy apetite, Calcium（Vancomycin, Ciprofloxacin, Clindamycin, Gen-sulphate（Plaster of Paris）
has been used as car-tamicin, Tobramycin）
were selected according torier of antibiotics for local delivery and ﬁller ofcommon organism responsible for the osteoar-

defect but have limitations of lack of osteointe-

ticular infection and culture & sensitivity.

gration and second surgery for removal. Al-

Twelve consecutive cases were treated. Surgicallograft bone material loaded with antibiotics

procedure and ﬁxation was performed wherever

may have advantage over them as it provides

required（Table ‒ 1）.

prolonged local antibiotic delivery, fills the de-Graft Preparation

fect and requires no second surgery for remov-

Allogenic bone graft was procured from con-al. Allograft bone loaded with antibiotics has

sented patients having undergone total hip andbeen used in in-vitro study by Eivind Witso etknee arthroplasty. Donors were pre screened17）

al using diﬀerent antibiotics and found to be ef-

for diseases and infection and graft was gamma

fective and safe. In an experimental animalsterilized with a dose of 25 grays of radiation at

13）

study by Shyam K Saraf et al using decal bonean accredited centre and stored at（−76 degree

matrix for local antibiotic delivery in experimen-

Celsius）
for minimum of three months before use

tal animal study and found it to be effective.

in institutional bone bank.

16）

Clinical study by Heinz Winkler have also

During surgery allogenic cancellous graft was

found use of antibiotic impregnated bone graft

manually morcelized and washed with plenty of

to be eﬀective and safe in one stage exchange ofsterile saline. The bacterial culture of the al-

infected hip replacement. Current study evalu-

lograft was taken before implantation to ascer-

ates further the eﬃcacy and safety of Allogenic

tain sterility. Morcellized bone graft was kept incancellous bone graft as local antibiotic carrier

20 ml distilled water solution consisting of anti-

in treatment of controlled osteoarticular infec-

biotic in concentrations（Table 2）
for a period oftion.

45‑60 minutes. Adjuvant autologous bone graft
Materials and Methods

The study was approved by institutional ethi-

was used in four cases, bone marrow aspirate inanother four cases and in rest four cases allogenic bone graft alone was used.

cal committee and all patients were fully in-

Postoperatively all patients were given usual

formed and agreed to participate in the study.

course of systemic antibiotic for seven days. Pa-

日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

Table 1．Case series study observation and out comeS n Diagnosis

Surgicalprocedure

AntibioticusedAdjuvant

Out come
Osteointegration Infection

Over all outcome

1

Infected partial Plate removal
union radius/ulna debridement
Plate in situ
ALBG

Vancomycin ABM

Healing of#ulna 5 Eradicatedmonths. Partial
osteointegrationin radius

Infection eradication
with healing

2

Infected NU S/ Debridement
F#bone loss ILN ALBG
in situ

Vancomycin Nil
Tobramycin

Gradual lysis ofbone graft 5 m.

Infection
eradicatedBone grafting exchange nailing union at
6m

3.

Segmental#Tibia ILN rotation
ﬂap ALBG

Vancomycin ABG

osteointegration
at 7 months

eradicated pri- Fracture union 6mary healing months

4

Atrophic infected ALBG Cortico- Vancomycin Nil
nonunion tibia# tomy ilizarov

Graft resorption
seen at 5 m

Infection
healedSecond procedure（7months later）
with
TENS＋ABM

5

S/C femur#bone ilizarov ALBG Vancomycin ABG
sinuses＋ABG
Tobramycin

osteointegration
at 8 months

Eradicatedhealed fracture with
infection eradication

6

Infected I/
T#with PFN in
situ

Vancomycin Nil

Gradual lysis ofgraft at 4 m

Serousdischarge
culture（-）

Improved bone quality,
required revised
ﬁxation7#Tibia with
Debridement
discharging sinus ALBG

Vancomycin ABM

Healing of
fracture

No further
sign ofinfection

Healing of fracture

8

Open#tibia
proximal third

ALBG, plating, Vancomycin- ABG
ﬂap rotation
Netlimycin

osteointegration eradicated pri- Fracture healing withseen at 5 months mary healing eradication of infection

9.

Osteomyelitis
tibia

Debridement
ALBG

Vancomycin ABM

improved bone
ﬁlling lesion

Vancomycin ABG

healing of defect EradicatedEradication of infection
with healing

Vancomycin- Nil
Gentamycin

lysis of bone
graft at 4 m

Ilizarov removed
fracture healed 8monthsVancomycin ABM

Lysis of graft,
Sterile dishealing of defect charge at 5day, healed
there after

Debridement＋AlBG

10 Osteomyelitis Hu- ALBG
merus
11 Infected
Open#tibia ext.
ﬁxater in situ

AlBG Flap
rotation
ilizarov

12 #S/F discharging Debridement
sinus
ALBG

EradicatedInfection
EradicatedHealed infection andbone

Eradication of infection
with healing

Abbreviations -#- fracture, I/T ‒ intertrochanter, NU ‒ non union, PFN ‒ Proximal femoral nail, BG ‒ bone
graft, ILN - Interlocking nail, ABM autologous bone marrow, S/F Shaft femur, T/F tibia-ﬁbula, TENs ‒ titanium
elastic nail, AlBG ‒ Allogenic Bone graft, ABG ‒ Autologous Bone graft, m - months

tients were followed regularly at appropriate interval. Particular attention was given to any
sign of infection / inﬂammation. Radiographs at

diological examination.
Results

intervals were done till completion of follow up

All the twelve patients could be followed forto determine the status of host bone and graft,

more than six months with a mean followup ofBone healing and osteointegration by Sloof et al

12 months（8 months ‑ 17 months）. None of the15）. Infection was assessed bycrieteria （Table 3）

patients showed clinical or histological evidence

clinical examination, blood investigation and ra-of any immunological reaction.
日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

Table 2．Eivind Witso et al3 Concentration of antibiotics solution used in the study
Antibiotic

Concentration

Vancomycin

50 mg/ml

Ciproﬂoxacin 2 mg/ml
Clindamycin

150 mg/ml

Tobramycin

75 mg/ml

Netlimicin

100 mg/ml

Teicoplanin

100 mg/ml

Osteointegration - Evaluated as per sloof et15）

al criteria. In four cases（two infected tibia-ﬁbula, one fracture shaft femur and one subtrochanter fracture）in which cancellous allograftwith antibiotics alone was used showed gradualcomplete resorption of bone graft in 16-20
weeks.（Figure -）without any sequestrum withimproved bone quality. Other four cases involv-

Fig. 1（a）
showing allograft stored in double jar,（b）
Graft reconstituted（c）Morcelised graft before andafter mixing with bone marrow（d）graft mixed with
antibiotic solution.

ing fractures of supra condylar femur, shaft femur, shaft Humerus and Tibia fibula in whichtion. Two patients required second time aug-

autologous bone graft was used as adjuvant

mentation with antibiotic impregnated allogenic

showed good healing and partial graft osteointe-bone graft with adjuvant（ autologous bone

gragion in immediate vicinity of the host bone

graft）to achieve infection eradication and bonewhile rest of the allograft gradually got re-healing. One patient of infected fracture tibia

sorbed in a mean time of 16.8 weeks（ 14‑22

ﬁbula developed serous discharge ﬁrst observed

weeks）. Among four cases with autologous bone

on 5th postoperative day which on culture re-marrow as adjuvant two（osteomyelitis and frac-vealed Pseudomonas aeruginosa. The patient

ture tibia fibula）gradually showed improved

was put on appropriate systemic antibiotic ther-bone quality, with allograft partial osteointegra-

apy for three weeks and there was no further

tion. One case of fracture shaft femur and otherclinical sign of infection. Another patient of frac-of fracture Tibia showed gradual complete re-ture subtrochanter femur with nail in situ fur-sorption of bone graft but with eradication of in-ther required debridement, secondary proce-

fection.

dures and change of fixation. No other case

Infection Eradication - Six patients healed primarily without requiring any further interven-developed any sign of infection.
Success rate of procedure in terms of infec-

Table 3．Sloof s Criteria13 for assessing osteointegration of allogenic bone graftsi.

Presence/Absence of progressive lucent lines between the preexisting bone and the graft.

ii. Absence of resorption of graftiii. Radiographic homogeneity of the graft.
日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

Fig. （2 a）skiagram showing infected non union supracondylar femur（b）treated by ilizarov & allogenic antibiotic
graft augmented with autograft（c）&（d）fracture healing osteointegration and infection eradication.

Fig. 3（a）showing infected fracture proximal tibia（b）treated with ﬁxation allogenic antibiotic graft augmented
with autograft（c）&（d）fracture healing osteointegration and infection eradication.

tion eradication without requiring any subse-

graft alone was used（fracture subtrochanter

quent procedure was 50 percent（ six out ofand one fracture tibia ﬁbula）
which required sec-

twelve cases）. Overall infection eradication was

ondary procedure and revised ﬁxation.

achieved in 10 out of 12 cases. Osteointegration
was achieved in all four cases in which autolo-

Discussion

gous bone graft was used as adjuvant and in

Earliest use of bone allograft for reconstruc-

50 ％ cases（two out of four）where autologous

tion has been practiced by Aubigne RM1）sincebone marrow aspirate was used. Two cases

1966. In most experimental models, fresh al-

were considered failure in which allogenic bonelografts are associated with a rigorous inflam日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

Fig. （4 a）showing infected shaft femur fracture intraoperative after debridement with bone loss（b）
grafted withallogenic antibiotic graft alone（c）&（d）gradual graft lysis（e）&（f）infection eradication, complete graft re-absorption without osteintegration.

matory response as well as a specific immune

blasts. Japaul S Gogia et al9）studied the eﬀect of

response. However, deep frozen allografts are

local antibiotic therapy in osteomyelitis. Kaki-

associated with decreased immunogenicity anduchi M et al10）also used the human bone matrix

no demonstrable change in initial mechanicalas alloimplant in local control of orthopedic in-

4）

properties as reported by Friedlander G in

fection and found eﬀective.
In our clinical study use of the allogenic mor-

1987.
The incorporation of antibiotic loaded bone7）

celized cancellous bone as a carrier of antibiotic

graft was ﬁrst studied by C. Gudmundson 1971

for prolonged elution in targeted area and facili-

who showed that the presence of tetracycline

tation of osteointegration was evaluated. Fur-

locally markedly inhibited bone graft incorpora-ther risk of allograft related graft infection astion. Use of one as a carrier for vancomycin has

described by Ketonis C et al11）can be obviated

17）
18）

vanco-

by combing the antibiotic with allograft. Use ofmycin is favoured because of its physiochemicalcancellous bone graft has advantage that it pro-

properties of hydrophilicity, heat stability andvides good substrate to absorb the antibiotic

eﬃcacy against Staphylococus species which isand adjuvant, it also get reabsorbed easily if not

most common cause of osteoarticular infection.

in cooperated without risk of further perpetua-

been studied in vitro by Witso E et al2）

Buttaro MA et al in 2003 showed in an in-vitro

tion of infection. Use of the adjuvant（Autologous

study that vancomycin if used in appropriatebone graft and bone marrow）
augment the heal-

concentration（1 gram dry vancomycin powder

ing potential of allograft as was observed infor 300 grams of bone graft.）will not affect os-

eight cases where adjuvants were used andteointegration of allogenic bone graft. Peak lev-

achieved favourable outcome in terms of os-

els attained locally by such a use were higher

teointegration. Extraossoues placed allogenic

than Minimum Inhibitory Concentration（MIC）

bone graft besides the fracture was inevitably

value of vancomycin for most susceptible organ-

got resorped in all the cases in a time period ofisms, but were 2000 times lower than the levels

14‑18 weeks.

（10,000 µg/ml）associated with death of osteo日本小児整形外科学会雑誌 Vol. 23, No. 2, 2014

Synthetic bone graft substitute such as calci-

Eﬃcacy of Antibiotic Impregnated Allogenic Bone Graft as Local Antibiotic Delivery System in Controlled Osteoarticular Infection

um phosphate, calcium sulphate etc has beenmented allogenic bone graft as carrier in con-14）

trolled osteoarticular infections appears to be

12）

Adl G, Mostafa MF and Shibuya K etal andnovel and eﬀective step in treating these dread-

showed better results when used in conjunction

ed infections. However graft integration oc-

with bone marrow which provide the osteo-in-

curred partially and may be attributed to infec-

ductive property to scaﬀold. Recent trends showtion related lyses as well as limited osteogenic

increasing use of the synthetic bone graft sub-potential of allogenic bone graft, hence its aug-

stitute8）due to wide commercial availability but,mentation with adjuvant such as autologous

do not demonstrated superiority of one overbone graft and or bone marrow is necessary toother. However synthetic substitute take long

improve outcome. However further studies andtime to reabsorbed or incorporated in host bed

larger case series are required for further vali-

hence may act as foreign body and after elution

dation.

also used in various studies by Siegel HJ , El4）of antibiotic and may lead to persistence of infection. Canellous allobone graft if not integrated
in host bed usually reabsorbed and prevent perpetuation of infection.

Acknowledgements
We sincerely acknowledge valuable suggestion and help by my collegue inder pawar, Rajat

In the present series no adverse eﬀect of anti-

Gupta, Lalchandani R, Ramavtar, Kuldeep,

biotic used in was observed. The two failure

Dogra S, Jindal M and Agarwal S. Administra-cases in the study group comprised of one es-

tive and research help from my institution ESI

tablished non union of mid diaphysial tibial frac-Hospital, Anestesiologist and radiologist for theirture and Sub Trochanter fracture belonged tovaluable contribution.

non union group which needed larger osteogenic potential which allogenic bone graft alone
may have lacked and required subsequent surgery with change of ﬁxation device. It appears
that in such situations use of allogenic bone
alone does not suffice and some osteogenic potentiator is also required to boost the alreadysluggish healing process. Intraoperative ﬁndings
were suggestive of increased vascularity at thefracture site with complete resorption of allograft and presence of bone defect. These ﬁndings are suggestive of allogenic bone graft being
able to induce an inﬂammatory reaction at thefracture site which may aid in healing process
but is not sufficient to bring about fracture
union as graft resorption occurred.
Conclusion

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