safe nail. use of a interlocking nail with a long acting antibiotic releasing core in patients with...

8/2/2019 SAFE Nail. Use of a Interlocking nail with a long acting antibiotic releasing core in patients with high infection risk. P

1/10

SAFE Nail. Use of a Interlocking nail with a long acting antibiotic releasing core in patients with high

infection risk. Prospective study in 27 cases.

Nuno Craveiro Lopes *, Carolina Escalda*,

*- Senior Orthopedic surgeon, Orthopedic Department, Garcia de Orta Hospital

Correspondence to:

Nuno Craveiro Lopes

Servio de Ortopedia e Traumatologia

Hospital Garcia de OrtaAv. Prof. Professor Torrado da Silva, Pragal

2801-951 Almada

PortugalFax: 351-212957004

Tel: 351-212727153

E-mail: [email protected]

Conflito of interests:

Nothing to declare

ABSTRACT

Introduction

The use of interlocking na

ils with PMMA cement impregnated with antibiotics is an attractive method for

treating or preventing infections of long bones. After conducting a in vitro pilot experimental study to evaluatethe stiffness of the nails, the levels of release of antibiotic and clinical efficacy of a modified interlocking nail,

with a core of PMMA cement impregnated with vancomycin, the Authors present the experience with the use

of a modified nail, filled with polymethylmethacrylate cement impregnated with 2 g of vancomycin (SAFE

Nail) to prevent and control infection in 27 cases at high risk.Material and Method

We prospectively evaluated 27 cases (8 femurs, 16 tibias and 3 knee arthrodesis), including 8 women and19 men, average age 42 years (range 15-69 years). 8 cases had open fractures, 11 presented with treatment with

external fixators that were converted into SAFE nail, 4 had limb length discrepancy and underwent lengtheningover a SAFE nail and 4 had osteomyelitis with fracture or nonunion.

In all cases it was used a Grosse nail with two longitudinal series of 5 mm holes, filled with 20 to 40 gr of

polymethylmethacrylate cement with 2 grams of vancomycin.The mean follow-up was 14 months (range 8-29 months). It was noted the time until consolidation, the

emergence of infection and intercurrences.Results

In 23 cases cultures were made prior to the nailing and potentially very aggressive bacteria was found in 17of these cases (74%).

In the overall of cases, there were two problems, five obstacles and no complications.In the group of 8 cases with open fractures, one developed a delayed consolidation, coming to fracture the

nail after 3 months. Substitution with SAFE DualCore nail (2nd generation), a reinforced nail, achievedconsolidation. Another patient developed a infection with MSSA resistant to vancomycin. Substitution with a

SAFE DualCore nail, loaded with cement with flucloxacilin achieved the consolidation and cure of the

infection.

In the group of 11 cases where conversion of external fixation to SAFE nail was done, consolidation wasachieved without the appearance of infection in all cases.

Of the 4 cases undergoing lengthening over SAFE nail, regenerated bone took more than three months to

consolidate in two cases and a fracture of the nail occurred. We proceeded to the replacement by a SAFEDualCore nail, resulting in the consolidation of the regenerate without the occurrencee of infection.


2/10

Finally, 4 cases with osteomyelitis of the tibia treated with a SAFE nail healed their infection.

Conclusions

The SAFE nail has proved extremely effective in the prevention and treatment of bone infection, when the

appropriate antibiotic can be used. Currently in cases where the bacteria is not known, we use two antibiotics,flucloxacillin and vancomycin.

In relation to its strength, it was observed that the SAFE nail supports 10% more load than Grosse nail and the

same 450,000 load cycles, corresponding to 3 months of use in ambulatory patients, what proved to be

insufficient for some patients who present late consolidation. To remedy this fact, changes were introduced in

order to reinforce the nail, creating the 2nd generation of SAFE nail called SAFE DualCore nail, whichsupports about 900.000 load cycles.

Keywords: Antibiotic; pin; infection, osteomyelitis, cement, PMMA, open fracture, bone lengthening

INTRODUCTION

The use of interlocking na

ils with PMMA cement impregnated with antibiotics is an attractive method fortreating or preventing infections of long bones. After conducting a in vitro pilot experimental study to evaluate

the stiffness of the nails, the levels of release of antibiotic and clinical efficacy of a modified interlocking nail,

with a core of PMMA cement impregnated with vancomycin, the Authors present the experience with the use

of a modified nail, filled with polymethylmethacrylate cement impregnated with 2 g of vancomycin (SAFE

Nail) to prevent and control infection in 27 cases at high risk.

Fig.1 - Injection of cement with antibiotics inside the nail involved with a

Esmach band.

MATERIAL AND METHODS

Twenty-seven consecutive cases who presented for treatment at our institution between January 2009 andDecember 2010 were included in this prospective study. The patients suffered from situations in which the

usual methods of treatment had a high risk of infection, for which, at the responsibility of the surgeon nail were

modified in order to be adapted to the particular situation of the patient.

It was eight women and 19 men with mean age of 42 years, ranging from 15 to 69 years. 8 femurs weretreated, 16 tibias and 3 arthrodesis of the knee. All patients were at high risk of infection or with current

infection, including 8 cases of open fractures, 11 cases of treatment with external fixators that were converted

into nailing, four cases of limb shortening where lengthening with external fixators over nail was and 4 cases of

osteomyelitis with fracture or bone loss(Table I).Of the eight open fractures (Fig. 2), 3 were Gustillo grade I, two grade II and 3 grade III [5]. The group of 11

cases treated with external fixation (Fig. 3) had the fixator on average 19 weeks (4-48 weeks). The group of 4

cases underwenting lengthening with external fixator over nail (Fig. 4) maintained the fixator for 12 to 16weeks for 4 and 5 cm lenghtenings. Of the four cases with osteomyelitis, three were secondary to nailing after

open fractures (Fig. 5) and one to a hematogenous osteomyelitis lasting between 2 months and 3 years. In all

cases presenting high debit drainage

. In three cases a Staphylococcus aureus was isolated, two methicillin-resistant

and on another patient a serracia marescencis.


3/10

Fig.2 - H.C., male, 47 years. Open fr GIII comminuted with 3 days of evolution. Nailing with SAFE Nail.

Appearance at 10 months.

In all cases a Grosse Stryker nail was used, adapted to the bone structure to be treated. The selected nail was

prepared in the workshops of the hospital with transfixing perforations of 5mm in diameter in the frontal plane

every 4 cm along the nail. At the beginning of the intervention in a sterile environment, the nail was involved in aEsmach band in tension and well reinforced in its proximal part. The cement is prepared in the usual way using 20

to 40gr of PMMA powder according to the internal volume of the nail to be used. 2 g of vancomycin and all of the

liquid component was added. Using a cement gun with the application tube cutted short and adapted solidly in theproximal nail hole, the cement was injected slowly inside the nail until it exit through the distal hole (Fig. 1). Then

the screw support of the proximal guide is screwed in in order to push the cement in the threaded area. Once the

cement gets pasty and before polymerization and heating, the screw is removed and the locking holes are cleaned

with a 4-5mm Steinmann pin.

Fig.3 - M.Q., female, 58 years. Reconstruction with the Ilizarov apparatus in a pseudoarthrosis after nail

failure. Reconversion to SAFE nail after 5 months of external fixation. Appearance at 15 months.

The technique of nailing and locking screws is similar to a normal interlocking nail, except that its introductioninto the medullary canal can not be made over the guide wire.

All patients received systemic antibiotic therapy, including 2 g of cefazolin and 80 mg of gentamicin every 8

hours for 3 days to prevent postoperative bacteremia.Patients leaved the hospital between the 3rd and 5th postoperative day and was controlled at the outpatient

clinic every 15 days and then monthly until consolidation. It was noted the time until the consolidation, the

emergence of infection and other intercurrences.

RESULTS

Exsudate cultures were performed prior to nailing in 25 cases, presenting 18 of these cases, potentially very

aggressive bacteria (74%). MSSA was isolates in 10 (40%), two MRSA, 2 Serratia, 2 Shigella (8% each), aPseudomonas, 1 Enterococcus (4% each), 5 cases had mixed skin flora (20%) and two cultures resulted negative.

All patients in the osteomyelitis group had positive cultures with aggressive bacteria, 37.5% of the open fractures,

54% of the conversions group and 75% of the lengthening group.


4/10

The mean follow-up was 14 months (range 8-29 months).

Fig.4 - F.H., male, 37 years. Failed TSRH self lengthening nail. Lengthening with external fixator over

nail. SAFE nail conversion after 3 months of external fixation. Appearance at 22 months.

In the group of 8 cases with open fractures (Fig. 2), we observed the development of delayed union in three

cases. In one case SAFE nail brooked at 3 months. A exchange with a SAFE DualCore nail was done (2nd

generation, reinforced with metal core and impregnated with 2gr of Vancomycin and 2gr of flucloxacillin),achieving consolidation. The remaining two cases had at the last follow up a delayed union with no signs of

infection (at 4 and 6 months). Another patient developed infection with vancomycin-resistant MSSA. Nailsubstitution was made with a SAFE DualCore nail, achieving the consolidation and cure of the infection.

In the group of 11 cases where reconversion of external fixation to SAFE nail was done (Fig.3), there wasdelayed union in two cases with infection control in all cases.

Fig.5 - J.N., male, 27 years. Osteomyelitis after nailing of a open fracture. Nailling with SAFE nail one

year after infection. Appearance at 2 and a half years of evolution

Of the four cases undergoing lengthening over a SAFE nail (Fig. 4), we detected delayed consolidation of the

regenerate with nail failure in 2 cases. A nail exchange with SAFE DualCore nail with bone graft in one patient,

lead to consolidation of the regenerate, with no occurrence of infection.

Finally, 4 cases with osteomyelitis of the tibia treated with SAFE nail (Fig. 5), achieved consolidation andhealed their infection without complications.

In the overall of the cases, there were two problems, 5 obstacles and no complications [26]: 3 cases had residual

infection of soft tissues appearing between 2 and 4 weeks after nailing, two with superficial lesions were treatedwith systemic antibiotic therapy with gentamicin and the third with a deep fistula, by surgical debridement and

placement of PMMA beads with Meropeneme. All have evolved to progressive closure of the lesions. A patient

with open fracture progressed to osteomyelitis by bacterial resistance to Vancomycin. He was treated withexchange of the SAFE nail to a SAFE DualCore nail with flucloxacillin, the antibiotic that the bacteria was

sensitive, and evolved to the cure of the infection. Finally, 3 cases (11%) developed delayed consolidation with a

failure of the SAFE nail. They have been treated with replacement with a SAFE DualCore nail, one of which with

cancellous bone graft taken from the contralateral femur with the RIA system [27].


5/10

DISCUSSIONBone infection requires a sequence of surgical procedures for infection control, to provide stability of the bone

structure and to promote the consolidation of the fracture, fragility, or bone loss. Traditional treatment includes serial

surgical debridement, various forms of systemic and local antibiotics and bone stabilization with external fixators, which

can later be converted into internal fixation once the infection had cleared [8,9,10]

The PMMA cement as spacers or beads impregnated with antibiotics has been used since 1970 [8,15,28,29] in the

treatment of bone infection, and has proved an effective method for long term local administration of high doses of

antibiotics [ 30], keeping minimal or undetectable systemic levels [6.12]. However, a second surgical procedure isneeded to remove the spacers or beads. Other type of carriers of antibiotics have been investigated to prevent the

need for a second surgical intervention and in some cases, to facilitate bone healing, including calcium sulfate and

various synthetic resorbable polymers [18,19,31,32,33, 34,35,36,37].

The safety of local treatment with PMMA cement loaded with antibiotics is well documented in clinical studies[8,15,18,19,28,29]. It is not available commercially PMMA cement with sufficient concentration of antibiotics for

local control of infections, the surgeon has to prepare it using most of the time, several antibiotics in high doses.

flucloxacillin and vancomycin proved to be the best combination in our midst because they have a broad spectrum

of action adapted to the most common bacterial flora, to be available in the market in powder form, having goodheat stability, good release properties and no effect on bone consolidation [18,31,38,39,40,41]. In addition to local

treatment, we administer parenteral antibiotics, including cefazolin and gentamicin for 3 to 4 days to prevent

postoperative bacteriemia.Most of our patients were treated with procedures that required the use of external fixators for prolonged periods. Itis well known in the literature [42,43,44,45], that in these situations there is a high prevalence of infection around

threaded pins and wires, muscle contractures and joint stiffness, pain and functional disability, and many patients

refuse treatment, they create intolerance to external fixators or are not good candidates because of exaggeratedobesity, intolerance or psychological instability. In these cases, the use of the SAFE nail brings an invaluable added

value.

Several authors reported other methods of combining an intramedullary device with PMMA cement

impregnated with antibiotics, including nails with beads [46.47], guide wires [26], Ender [16], Kntscher [48]andinterlocking nails[17] covered with PMMA cement with antibiotics. However they all had problems, obstacles and

complications in large number, including necessity to remove the beads, to include other mean of stabilization with

external immobilization, replacement with a more stable nail in a second timing or because of debonding of thecement outside the nail during insertion or extraction, leading to blockage of the nail and cement inside themedullary canal.

The SAFE nail was easy to manufacture and the procedure of filling it with cement impregnated with

antibiotics is fast and easy to perform by one of the surgeons, taking about 10 minutes, while the other surgeonprepare the implant site.

In this group of patients, the SAFE nail has been very effective in preventing infection and treating open

fractures, conversion of external fixation into internal, to do lengthening over nail and to treat osteomyelitis of long

bones with bone fragility. All these situations usually require long periods of external fixation and often serialsurgeries.

It is well documented that the placement of intramedullary PMMA cement impregnated with antibiotics is very

effective in the prevention and treatment of osteomyelitis, because it releases locally prolonged and high doses ofantibiotics [8,9,18,28,29,31,38,39,40,41]. However the fact that systemic levels of antibiotics are minimal orundetectable [20,21], makes this form of administration by itself insufficient to control the residual soft tissue

infection. These infections, which often accompany the process of osteomyelitis, become isolated from the

intramedullary environment after 2 weeks of treatment through the bone healing process. So it is necessary tosupplement the treatment with appropriate antibiotics, administered systemically or locally in the form of PMMA

cement beads with antibiotics.

Table I pre and posoperative patient data


6/10

N Name Age/Sex Date Segment Observations Initial Treat. Contamination FW Result

Grup 1 (Open Fractures)

1 JM 57/M 08/2009 Tibia Distal GII SAFE 3 weeks 22 Consolidation. No Infection

2 GW 51/M 11/2009 Tibia Segmental GI SAFE

9 days

MSSA

Flucloxacylin

19 Infection Strep B Hem

Substitution SAFE DualCore

Consolidation

3 MS 61/F 07/2010 TibiaMedial Cominutive GIII

ObeseSAFE

7 days

Pseud. Aerug.

Gentamycin

11 Late Consolidation

# nail - 3 months No Infection


4 TS 23/M 07/2010 Tibia Distal Cominutive GI SAFE 2 days 11 Consolidation. No Infection

5 HC 47/M 08/2010 Tibia Medial Cominutive GIII SAFE

3 days

MSSA

Entero.Cloacae

Fluclo+Genta

10 Consolidation.

No Infection

6 LS 38/M 08/2010 Femur Diafisal. Gun fire GI SAFE4 days 10 Consolidation.

No Infection

7 PC 35/M 08/2010 Tibia Medial GII SAFE2 days

Mix flora

2 Infection soft tissues

Late Consolidation

No Infection ssea

8 CF 17/M 12/2010 Tibia Distal GIII SAFE15 days

Negativo


No Infection

Grup 2 (Reconversion from External Fixation)

9 MS 37/F 03/2010 Femur Pseudartrose

Shortening. 3cm

Ilizarov

4 months

Shigella Spp.

MSSAMeropenem

15 Consolidation.

No Infection

10 JS 42/M 12/2010 Tibia Fr. segmentar GIII Fix.Ex.AO5 months

Mix flora


No Infection

11 AR 49/M 04/2009 Tibia Fr. segmentar GIII ExFixAO1 Month

Mix flora

26 Consolidation.

No Infection

12 CF 66/M 11/2010 Knee

Inf. PTK. Spacer + revision

+ ExFix AO.

Shortening 6 cm

Ilizarov

8 months

MSSA

Flucloxacylin

7 Consolidation.

No Infection

13 JO 69/M 12/2010 Knee

Inf. PTK. Spacer + revision

+ ExFix MonoTube.

Shortening 5 cm

Ilizarov

4 months

Serrat. Maresc

Gentamycin


Late consolidation

No bone Infection

14 EJ 48/F 02/2010 KneeKnee Instability.

PoliomyelitisIlizarov

3 months

MSSA

Flucloxacylin

16 Consolidation.

No Infection

15 MQ 58/F 03/2010 Femur Pseudartrose distal

Shortening. 5cmIlizarov

5 months

Negative

15 Consolidation.

No Infection

16 CG 56/M 10/2009 Tibia Fr. Distal GII Ilizarov2 months

Mix flora

20 Consolidation.

No Infection

17 JS 42/M 12/2010 Femur Cominutive . distal GII Ilizarov5 months

Mix flora

13 Consolidation.

No Infection

18 SR 25/F 10/2010 Femur Distal Pseudartrosis.

ObeseIlizarov

4 months

MSSA

Flucloxacylin

8 Consolidation.

No Infection

19 MS 38/F 12/2010 Tibia Bone loss 10cm Ilizarov

1 ano

Shigella Spp

Meropeneme


Consolidation

No bone Infection

Grup 3 (Bone lenghtening)

20 AC 18/F 11/2010 Femur

Shortening after osteomielytis

Shortening 4 cm ExFix+ SAFE 3 months

7 Consolidation.

No Infection

21 VA 15/M 09/2010 Femur Resseco de Ewing

Shortening 4cmExFix+ SAFE

3 months

MSSA

Flucloxacylin




22 SD 51/M 11/2010 Femur Pseudartrose. proximal

Shortening 5cmExFix+ SAFE

4 months

MRSA

Vancomicina

7 Atrophic regenerate



and bone graft

23 FH 37/M 08/2009 Femur Aneurismatic bon cyst

Shortening 4cmTSRH nail

3 months

MSSA

Flucloxacylin

22 Consolidation.

No Infection

Grup 4 (Osteomyelitis with bone fragility)

24 FR 36/F 01/2009 Tibia Open fracture nailing. Medial Grosse nail

4 months

MSRA

Gentamycin

29 Consolidation.

No Infection


7/10

N Name Age/Sex Date Segment Observations Initial Treat. Contamination FW Result

25 CR 16/F 09/2009 Tibia Hematogenic Proximal SAFE nail

3 years

MSSA

Flucloxacylin

21 Consolidation.

No Infection

26 JN 27/M 01/2009 Tibia Open fracture nailing. Medial Ilizarov

1 year

Serracia Mares

Gentamycin


Consolidation

No Infection ssea

27 GT 51/M 01/2010 Tibia Open fracture nailing. Medial Grosse nail

3,5 months

MSSA

Flucloxacylin

17 Consolidation.

No Infection

In three cases we observed the reappearance of active soft tissue fistula after 2 weeks of treatment, whichprogressed to healing with systemic antibiotic therapy in two cases and the other case with use of PMMA cementbeads impregnated with antibiotic.

The levels of the bending forces that are exerted on the femur and tibia of an adult in their normal activities

represents up to 0.6 times the body weight when walking (40 kg) and 1.3 times when climbing stairs (100 kg) [24].

These bending forces never are reached in a patient with lower limb pathology underwent a nailling of the femur ortibia and using cruches. On the other hand, it is described that intramedullary nails have a lifespan of about 450 to

500,000 load cycles, which corresponds to about 3 to 4 months of use, leading to its failure in the meantime if there

is no bone consolidation [25 ].

The rate of delayed consolidation and pseudarthrosis after internal fixation of the closed fractures of the tibia,varies from 5 to 13%. It is known that this rate increases exponentially when it comes to an open fracture, reaching

up to 47% in Gustillo grade I and II and 74% in grade III [49].

In the group of 27 cases we treated, there was need for a second surgery procedure in 5 cases (18.5%),including 3 nail failures (11%) after 3 months in patients with delayed consolidation . This number is acceptable

and low comparatively to the data of other authors and given the severity and high risk of complications and

additional surgeries associated with alternative treatment with prolonged external fixation. [45].

Fig.6 Method for extraction of broken nail, using:

a) a retrograde 3mm Kirschner wire to push, or

b) an anterograde 5mm threaded pin to pull

In three cases it was necessary to remove broken SAFE nails, the procedure was easy to perform using a 3mm

Kirschner wire inserted retrograde, through the intercondylar notch of the femur or the calcaneus, to push

proximally the distal fragment of the broken nail, or a threaded pin, anterograde, to pull the distal fragment (Fig.6).In the overall of the 27 cases, there were two problems, 5 obstacles and no complications.

To avoid the obstacles that arose, modifications were introduced to the nail to reinforce it and give more

resistance to fatigue and simultaneously to increase the spectrum of action and dose of antibiotics, leading to the

2nd generation of SAFE nails, called SAFE DualCore nail.


8/10

CONCLUSIONS

The authors conclude that this device, an example of a new class of implants - implants biologically active, can

represent an added value compared to current methods of treatment of open fractures, conversions of externalfixation in internal fixation and treatment of bone infections with weakening or bone loss. The procedure is simpler

and faster, the nail is more resistant than the normal nails, allowing the choice of appropriate antibiotic with local

release of high doses and prolonged treatment, able to establish a suppressive antibiotic therapy, thus avoiding the

recurrence of infection, with less intercurrences than similar methods.

In the treated patients, the SAFE nail has proved extremely effective in the prevention and treatment of boneinfection, when the appropriate antibiotic can be used. Currently in cases where the bacteria are not known, we use

two antibiotics, flucloxacillin and vancomycin.

In relation to its strength, it was observed that with a bending load of 40 to 80 kg, it is 10% stronger than thecorrespondent standard Grosse nail. Its resistance to fatigue showed, however, to be insufficient for some patients

who have delayed consolidation. To remedy this fact, modifications were introduced to the nail so as to reinforce it

and give more resistance to fatigue, giving rise to the 2nd generation of SAFE nails, called SAFE DualCore nail.

BIBLIOGRAPHY

1 - Court BC. Antibiotic prophylaxis in orthopaedic surgery. Scand J Infect Dis 1990;70(Suppl):749.2 - Simpson A H, Deakin M, Latham J M. Chronic osteomyelitis. The effect of the extent of surgical resection on

infection-free survival. J Bone Joint Surg (Br) 2001; 83 (3):403-7.3 - Ikpeme IA, Ngim NE, Ikpeme AA. Diagnosis and treatment of pyogenic bone infections. African Health

SciShorteninges 2010; 10 (1): 82 88.4 - Rohde H, Frankenberger S, Zhringer U, Mack D. Structure, function and contribution of polysaccharide

intercellular adhesin (PIA) to Staphylococcus epidermidisbiofilm formation and pathogenesis of biomaterial-

associated infections. Eur J Cell Biol 2010;89:103-1115 - Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: A

new classification of type III open fractures. J Trauma. 1984;24:742.

6 - Maurer-DJ; Merkow-RL; Gustilo-RB. Infection after intramedullary nailing of severe open tibial fractures

initially treated with external fixation. J-Bone-Joint-Surg-Am. 1989;71(6): 835-87 - McGraw JM, Lim EV. Treatment of open tibial-shaft fractures. External fixation and secondary intramedullary

nailing. J-Bone-Joint-Surg-Am. 1988;70(6): 900-118 - Klemm K. Gentamicin-PMMA-beads in treating bone and soft tissue infections. Zentralbl Chir. 1979; 104:934-

942.9 - Scott DM, Rotschafer JC, Behrens F. Use of vancomycin and tobramycin polymethylmethacrylate

impregnated beads in the management of chronic osteomyelitis. Drug Intell Clin Pharm. 1988;22(6):480-3.

10 - Evans RP,Nelson CL. Gentamicin-impregnated polymethylmethacrylate beads compared with systemicantibiotic therapy in the treatment of chronic osteomyelitis. Clin Orthop Relat Res. 1993;295:37-42.

11 - Calhoun JH, Henry SL, Anger DM, Cobos JA, Mader JT. The treatment of infected nonunions with

gentamicin-polymethylmethacrylate antibiotic beads. Clin Orthop Relat Res. 1993;295:23-7.

12 - Bowyer GW, Cumberland N. Antibiotic release from impregnated pellets and beads. J Trauma.1994;36(3):331-5.

13 - Schmidmaiera G, Luckea M, Wildemanna B et al., Prophylaxis and treatment of implant-related infections byantibiotic-coated implants: a review. Injury, 2006;37:2:S105-S112.

14 Romano CL, Giammona G, Giardino R et al Antibiotic-loaded resorbable hydrogel coating for infectionprophylaxis of orthopaedic implants. Preliminary studies. J Bone Joint Surg Br, 2011 93:S337-S338.

15 - Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg.

1970;41:511-515.

16 - Ohtsuka H, Yokoyama K, Higashi K, et al., Use of antibiotic impregnated bone cement nail to treat septicnonunion after open tibia fractures, J TRAUMA. 2002;52:364-366.

17 Thonse R and Conway JD. Antibiotic Cement-Coated Nails for the Treatment of Infected Nonunions and

Segmental Bone Defects. J Bone Joint Surg Am. 2008;90:163-174.
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Scott%20DM%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Rotschafer%20JC%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Behrens%20F%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Evans%20RP%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Evans%20RP%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Nelson%20CL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Calhoun%20JH%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Anger%20DM%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cobos%20JA%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mader%20JT%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Bowyer%20GW%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cumberland%20N%22%5BAuthor%5Dhttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/issues?Vol=37http://www.ncbi.nlm.nih.gov/pubmed?term=%22Scott%20DM%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Rotschafer%20JC%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Behrens%20F%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Evans%20RP%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Nelson%20CL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Calhoun%20JH%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Anger%20DM%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cobos%20JA%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mader%20JT%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Bowyer%20GW%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cumberland%20N%22%5BAuthor%5Dhttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstracthttp://www.injuryjournal.com/article/S0020-1383(06)00187-2/abstract#aff1http://www.injuryjournal.com/issues?Vol=37


9/10

18- Zalavras CG, Patzakis MJ, Holtom P. Local antibiotic therapy in the treatment of open fractures and

osteomyelitis. Clin Orthop Relat Res. 2004;427:86-93.

19- Mader JT, Stevens CM, Stevens JH, Ruble R, Lathrop JT, Calhoun JH. Treatment of experimental

osteomyelitis with a fibrin sealant antibiotic implant. Clin Orthop Relat Res. 220;403:58-72.20- Nelson CL, Griffin FM, Harrison BH, Cooper RE. In vitro elution characteristics of commercially and

noncommercially prepared antibiotic PMMA beads. Clin Orthop Relat Res. 1992;284:303-9.

21- Adams K, Couch L, Cierny G, Calhoun J, Mader JT. In vitro and in vivo evaluation of antibiotic diffusion

from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res. 1992 May;(278):244-52.

22- Bayston R, Milner RD. The sustained release of antimicrobial drugs from bone cement. An appraisal oflaboratory investigations and their significance. J Bone Joint Surg Br. 1982;64(4):460-4.

23- Eckman JB Jr,Henry SL,Mangino PD, Seligson D. Wound and serum levels of tobramycin with the

prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. ClinOrthop Relat Res. 1988 Dec;(237):213-5.

24- William R. Taylor, Markus O. Heller, Georg Bergmann, Georg N. Duda. Tibio-femoral loading during human

gait and stair climbing. Journal of Orthopaedic Research, 2006;22:3

25- Perren, SM.The biomechanics and biology of internal fixation using plates and nails. Orthopedics,1989;12:21-

34.(tempo de consolidao 500.000 ciclos)

26- Paley D, Herzenberg JE. Intramedullary infections treated with antibiotic cement rods: preliminary results in

nine cases. J Orthop Trauma. 2002;16:723-9.

27 Newman JT, Stahel PF, Smith WR et al. A new minimally invasive thechnique for large volume bone graftharverst for treatment of fracture nonunions. Orthopedics, 2008;31:257

28- Beals RK, Bryant RE. The treatment of chronic open osteomyelitis of the tibia in adults. Clin orthop Relat Res.

2005;433:212-7.29- Henry SL, Ostermann PA, Seligson D. The prophylactic use of antibiotic impregnated beads in open fractures.

J Trauma. 1990;30:1231-8.

30- Ostermann PA,Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085consecutive cases.J Bone Joint Surg Br.1995 Jan;77(1):93-7.

31- Hanssen AD. Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop

Relat Res. 2005;437:91-6.

32- Hendricks KJ, Lane D, Burd TA, Lowry KJ, Day D, Phaup JG, Anglen JO. Elution characteristics of

tobramycin from polycaprolactone in a rabbit model. Clin Orthop Relat Res. 2001;392:418-26.33- Rutledge B, Huyette D, Day D, Anglen J. Treatment of osteomyelitis with local antibiotics delivered via

bioabsorbable polymer. Clin Orthop Relat Res. 2003;411:280-7.

34- Grsel I, Korkusuz F, Tresin F, Alaeddinoglu NG, Hasirci V. In vivo application of biodegradable controlledantibiotic release systems for the treatment of implant- related osteomyelitis. Biomaterials. 2001;22:73-80.

35- Shirtliff ME, Calhoun JH, Mader JT. Experimental osteomyelitis treatment with antibiotic-impregnated

hydroxyapatite. Clin Orthop Relat Res. 2002;401:239-47.36- Ambrose CG, Clyburn TA, Louden K, Joseph J, Wright J, Gulati P, Gogola GR, Mikos AG. Effective

treatment of osteomyelitis with biodegradable microspheres in a rabbit model. Clin Orthop Relat Res.

2004;421:293-9.

37- Tresin F, Grsel I, Hasirci V. Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in

vitro antibiotic release. J Biomater Sci Polym Ed. 2001;12:195-207.38- Patzakis MJ, Zalavras CG. Chronic posttraumatic osteomyelitis and infected nonunion of the tibia: current

management concepts. J Am Acad Orthop Surg. 2005;13:417-27.

39- van Raaij TM, Visser LE, Vulto AG, Verhaar JA. Acute renal failure after local gentamicin treatment in aninfected total knee arthroplasty. J Arthroplasty. 2002;17:948-50.

40- Perry AC, Prpa B, Rouse MS, Piper KE, Hanssen AD, Steckelberg JM, Patel R. Levofloxacin and

trovafloxacin inhibition of experimental fracture-healing. Clin Orthop Relat Res. 2003;414:95-100.

41- Lindsey RW, Probe R, Miclau T, Alexander JW, Perren SM. The effects of antibiotic-impregnated autogeneiccancellous bone graft on bone healing. Clin Orthop Relat Res. 1993;291:303-12.

42- Bose WJ, Gearen PF, Randall JC, Petty W. Long-term outcome of 42 knees with chronic infection after total

knee arthroplasty. Clin Orthop Relat Res. 1995;319:285-96.
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Adams%20K%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Couch%20L%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cierny%20G%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Calhoun%20J%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mader%20JT%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Bayston%20R%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Milner%20RD%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Milner%20RD%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Eckman%20JB%20Jr%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mangino%20PD%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Seligson%20D%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Ostermann%20PA%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Seligson%20D%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Seligson%20D%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Adams%20K%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Couch%20L%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Cierny%20G%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Calhoun%20J%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mader%20JT%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Bayston%20R%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Milner%20RD%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Eckman%20JB%20Jr%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Mangino%20PD%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Seligson%20D%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Ostermann%20PA%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Seligson%20D%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20SL%22%5BAuthor%5D


10/10

43- Green SA. Complications of external skeletal fixation. Clin Orthop Relat Res. 1983;180:109-16.

44- Herzenberg JE, Scheufele LL, Paley D, Bechtel R, Tepper S. Knee range of motion in isolated femoral

lengthening. Clin Orthop Relat Res. 1994;301:49-54.

45- Paley D. Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin OrthopRelat Res. 1990;250:81-104.

46- Tandon SC, Thomas PB. Persistent osteomyelitis of the femur2 cases of exchange intramedullary nailing

with gentamicin beads in the nail. Acta Orthop Scand. 1996;67:620-2.

47- Sundgren K. Cemented modular intramedullary nail in failed knee arthroplastya report of 2 cases. Acta

Orthop Scand. 1999;70:305-7.48- Grimer RJ, Belthur M, Chandrasekar C, Carter SR, Tillman RM. Two-stage revision for infected

endoprostheses used in tumor surgery. Clin Orthop Relat Res. 2002;395:193-203.

49- Audigl L, Griffin D, Bhandari M et Al. Path analysis of factors for delayed healing and non-union in 416operatively treated tibial shaft fractures. Clin Orthop. Relat. Res. 2005;438:221-322.

safe nail. use of a interlocking nail with a long acting antibiotic releasing core in patients with...

Documents