Authors

EAST Practice Management Guidelines Work Group

Fred A. Luchette, MD, University of Cincinnati Medical Center, Cincinnati, OH
Lawrence B. Bone, MD, State University of New York at Buffalo, Buffalo, NY 
Christopher T. Born, MD, University of Pennsylvania Health System, Philadelphia, PA 
William G. DeLong, Jr, MD, University of Pennsylvania Health System, Philadelphia, PA
William S. Hoff, MD, University of Pennsylvania Health System, Philadelphia, PA 
Daniel Mullins, PhD, University of Maryland School of Pharmacy, Baltimore, MD 
Francis Palumbo, PhD, JD, University of Maryland School of Pharmacy, Baltimore, MD 
Michael D. Pasquale, MD, Lehigh Valley Hospital and Health Network, Allentown, PA 

Address for Correspondence and Reprints:

Fred A. Luchette, MD D
epartment of Surgery ML-0558 
231 Bethesda Avenue 
Cincinnati, Ohio 45267-0558 
Phone: (513)-558-5661 
Fax: (513)-558-3136 
E-mail:Fred.Luchette@uc.edu

I. Statement of the Problem

Extremity fractures are caused by either low or high energy forces and may be isolated or combined with other injuries. When the underlying fracture is associated with a cutaneous wound, prevention of wound sepsis remains the primary objective in the management of the soft tissue. There is universal agreement that these wounds require emergency treatment as soon as possible to minimize infectious complications. To help standardize care and comparison of similar injuries in studies, Gustilo et al.^[1] classified open fractures into three categories:

Grade (Type) I: Open fracture with a skin wound less than 1 cm long and clean.

Grade (Type) II: Open fracture with a laceration more than 1 cm long without extensive soft tissue damage, flaps, or avulsions.

Grade (Type) III: Either an open segmental fracture, an open fracture with extensive soft tissue damage, or a traumatic amputation.

In their review, the infection rate for type III open fractures was a major problem with an incidence of 24%. Grade III fractures encompassed a wide range of soft tissue wounds and was felt to be too imprecise for standardizing care and comparison. Thus, Gustilo further stratified these wounds according to worsening prognosis with a wound sepsis rate as follows: IIIa - 4%; IIIb - 52%; IIIc - 42%.^[2]

IIIa: Adequate soft tissue coverage of a fractured bone despite extensive soft tissue laceration or flaps, or high energy trauma irrespective of the size of the wound.

IIIb: Extensive soft tissue injury loss with periosteal stripping and bone exposure, usually associated with massive contamination.

IIIc: Open fractures associated with arterial injury requiring repair.

The importance of describing type III open fractures with this more accurate classification scheme cannot be overstated. This A/B/C stratification also allows for subsequent upward revision for a wound which evidences progressive soft tissue necrosis following initial evaluation. Although this scoring system is the one most widely used for management decisions and comparison of results of treatment among different series, a recent report has claimed that interobserver agreement is moderate to poor and is case dependent.^[3]

An appropriate management plan for open extremity fractures would include coverage with a sterile dressing with gentle pressure applied as necessary to control bleeding. Splinting is carried out, the patient is prophylaxed for tetanus and parenteral antibiotics are administered. Operative wound care should be done under general or regional anesthesia as soon as the patient has been stabilized and cleared for the operating room. Whenever possible, delays of more than six hours should be avoided because of the increased risk of infection. Wound care should involve a thorough debridement of devascularized muscle, fascia, subcutaneous tissue, skin, bone and all foreign material. The importance of adequate surgical debridement can not be overemphasized in controlling wound sepsis since antibiotics are only adjunctive therapy. Determination of the fracture grade should be made at this time. The margins of the wound of compounding are extended as required for debridement and appropriate stabilization of the fracture is effected. The wound is left open under a sterile moisture retaining dressing. A “second-look” may be advisable at 24-48 hours with further debridement if necessary. Ultimately, wound closure may be accomplished by delayed primary closure, split thickness skin graft, local muscle flap rotation, or free tissue transfer with microvascular anastomosis.

Various factors have been recognized as increasing the risk for infection: (1) failure to utilize prophylactic antibiotics; (2) resistance of wound organisms to wound antibiotics; (3) increased time from injury to initiation of antimicrobial agent and operative debridement; (4) extent of soft tissue damage; (5) open tibial fractures; (6) positive post debridement-irrigation cultures; and (7) wound closure in the presence of Clostridium perfringens. Other factors shown to have no effect include the length of antibiotic treatment (3 versus 5 to 10 days) and type of wound closure. Stabilization is now usually obtained by unreamed nailing or external fixation.^[4] Low infection rates have been reported after severe open fractures treated by reamed intramedullary nailing.^[5] Dellinger et al. performed a multivariate logistic regression analysis and identified local factors at the fracture site as more significant risk factors for subsequent infection than Injury Severity Score (ISS), the requirement for blood transfusion, the amount of blood transfused, or the presence of more than one fracture.^[6]

Norden found convincing evidence that antibiotics administered before incision reduced the risk of infection after surgical stabilization of closed hip fractures or proximal femoral endoprosthetic replacement.^[7] The group receiving antibiotics had a 78% lower rate of infection compared with controls. This study was included in this review to demonstrate the role of prophylactic antibiotics following orthopedic procedures for closed fractures. However, Norden did not address the role of prophylactic antibiotics with regard to open fractures in which bacterial contamination is present preoperatively in 48% to 60% of all wounds and 100% of severe wounds.

Dellinger provided an in depth report of prophylactic antibiotics in open fractures in 1991.^[8] He performed a detailed analysis of controlled trials in open fractures and the various studies evaluating choices of antibiotics as well as duration of therapy for these extremity injuries. Subsequent  nvestigations have been carried out to analyze the impact of various antibiotic regimens and the appropriate length of time for continuing therapy.^{[15-17] [22]}

II. Process

A. Identification of references

These recommended guidelines for prophylactic antibiotic usage for open fractures are evidence-based. Articles were identified from the literature by independent searches performed by two of the reviewers. One search was performed using OVID MEDLINE and covered the literature from 1985 to 1997. Key words used in this search were “open fracture, antibiotics, prophylaxis, and management”. References from 1975 to 1985 were identified through a MEDLINE search using the following key words: “antibiotic prophylaxis; human; open fractures; bacterial infections - prevention and control; fracture healing; fracture-complications; and surgical wound infections”. These combined searches identified 313 articles. The bibliography of each article was reviewed for additional references which were not identified in the two original searches. Letters to the editors, case reports, and review articles were excluded from further evaluation. This identified 56 studies for evidentiary review. The articles were reviewed by 3 orthopedic trauma surgeons, 2 general surgeons, and two pharmaceutical outcome researchers with interest in pharmacokinetics and health care economics. These individuals then collaborated to produce the guidelines.

1. Quality of the references

The references were classified in the methodology established by the Agency for Health Care Policy and Research (AHCPR) of the U.S. Department of Health and Human Services. Additional criteria and use for Class I articles were taken from a tool described by Oxman et al.9 Thus, the classifications were:

Class I: Prospective, Randomized, Double-Blinded Study

Class II: Prospective, Randomized, Non-Blinded Trial

Class III: Retrospective Analysis of Patient Series

III. Recommendations

A. Level I

There are sufficient Class I and II data to recommend preoperative dosing with prophylactic antibiotics (as soon as possible after injury) for coverage of gram positive organisms as optimum care for trauma patients with open fractures. For Grade III fractures, additional coverage for gram negative organisms should be given. High-dose penicillin should be added to the antibiotic regimen when there is a concern for fecal/Clostridial contamination such as in farm related injuries.

B. Level II

There are sufficient Class I and Class II data to recommend antibiotics be discontinued 24 hours after wound closure for Grade I and II fractures. For Grade III wounds, the antibiotics should be continued for only 72 hours after the time of injury or not more than 24 hours after soft tissue coverage of the wound is achieved, whichever occurs first (See page 10, paragraph C for discussion).

Definition of Level I recommendation: This recommendation is convincingly justifiable based on the available scientific information alone. It is usually based on Class I data, however, strong Class II evidence may form the basis for a level 1 recommendation, especially if the issue does not lend itself to testing in a randomized format. Conversely, weak or contradictory Class I data may not be able to support a level 1 recommendation.

Definition of Level II recommendation: This recommendation is reasonably justifiable by available scientific evidence and strongly supported by expert critical care opinion. It is usually supported by Class II data or a preponderance of Class III evidence.

IV. Scientific Foundation

A. Historical background

An open fracture was for many thousands of years a sentence of death. Amputation was often considered as the only viable alternative to death. The mortality rate of all kinds of open fractures in the Franco Prussian War was 41%; it was 50% for the lower leg, 66% for the thigh, and 77% for open fractures of the knee joint. Other reports claimed a mortality rate ranging from 54 to 99% for open femur fractures.^[10]

In War World I, the mortality rate for an open fracture of the femur remained approximately 80%. The immediate use of the Thomas splint for femur fractures was introduced in 1916, and the mortality rate for open fractures of the femur fell promptly to 16%. Karpmen later recognized that restoration of the bone length reduced the volume of the fascial compartments and therefore the magnitude of blood loss associated with the open fracture, which explained the reduction in mortality observed with the Thomas splint. Also in World War I, Orr evolved a policy of wound excision and debridement, reduction of the fracture, stabilization with plaster, and leaving the traumatic wound open.^[11] During the Spanish Civil War, Truetta confirmed Orr’s experience with a reported 0.6% septic mortality rate in 1069 open fractures.^[12] Thus, World War I was the first time that the role of wound debridement was correlated with a reduction in septic mortality for open fractures. This reduction occurred prior to antibiotics, blood transfusions, intravenous fluids, and modern anesthesia.

During World War II, there was initial enthusiasm for the use of chemotherapeutic agents primarily in the form of sulfonamides in the immediate care of open fractures. The importance of wound excision with debridement and healing by secondary intention was once again appreciated when antibiotics failed to reduce infectious complications when wounds were primarily closed. The role of delayed primary wound closure was evaluated in 25,000 wounds without antibiotic coverage. There was a 95% success rate in wounds left open for 4 to 10 days despite positive bacterial cultures from the wound.^[13]

Patzakis et al. were the first to perform a prospective, randomized study comparing the infectious rates for penicillin with streptomycin, cephalothin, and placebo.^[14] The rates were 13.9% for controls, 9.7% for penicillin, and 2.3% for cephalothin. Unfortunately, the study was not doubleblinded and did not grade for severity of open fractures. Nonetheless, it was the first report showing a benefit of prophylactic antibiotics in these severe extremity injuries. Since the Patzakis study, there have been multiple reports^{[14] [15] [20] [26] [27] [32] [35] [37] [44] [61] [63]} comparing various antibiotic regimens for efficacy in reducing infections and durations of therapy. These articles did stratify for grade of open fracture and form the basis for this evidence-based outcome review.

B. Choice of antibiotic

The majority of studies contain populations of patients with various mechanisms of injury. Hansraj et al.15 performed a non-blinded comparison of ceftriaxone to cefazolin in extra-articular bony injuries due to gunshot wounds. The mean time between injury and the initial antibiotic dose was 4 hours. All admission cultures were negative, and none of the patients subsequently developed clinical signs of infection. They concluded that the cost of therapy was significantly less with ceftriaxone and resulted in a 1-day reduction in length of stay.^[15] This study questions whether low velocity missile injury to extra-articular cortical bone requires any antibiotic prophylaxis.^[15] If one feels compelled to use a prophylactic antibiotic in this low-risk group, the authors suggest a singledose, long-acting antimicrobial is cost effective in this patient population compared with a shorteracting, first generation cephalosporin which requires multiple dosing.

The benefit of antibiotic coverage in gunshot wounds producing skeletal fractures has also been evaluated in children.^[16] Most of these wounds were caused by low velocity missiles.  Forty-five patients (59%) received a first generation cephalosporin for 48 hours. None of these patients developed an infectious complication. The authors concluded that children with Grade I and II open fractures produced by low velocity missiles require antibiotics for only 48 hours.

Hope and Cole evaluated the role of antibiotics in children with open tibial fractures.^[17] Despite broad-spectrum antibiotics for at least 48 hours, the wound infection rate was 11%. However, the most important variable in these infections was felt to be the severity of the soft tissue injury rather than the antibiotic coverage.^[17] In a similar review of open tibial fractures in children, Buckley et al. reported a wound infection rate of 7.3%, osteomyelitis was 4.9%, and pin track infection was 20%.^[18] Antibiotics were administered for 48-hour intervals and were repeated with subsequent wound debridement. They concluded the most important variable in reducing wound infection was utilizing delayed wound closure rather than primary closure.^[18] Patzakis and Wilkins retrospectively reviewed their experience with various antibiotic regimens including penicillin, cephalothin, and cefamandole as well as a control arm with no antibiotics.^[19] They also looked at the infection rate for adults (7.2%) and pediatric patients (1.8%). The various infectious complication rates were 13.9% for placebo, 10% for penicillin plus streptomycin, 5.6% for cephalothin, and 4.5% for cefamandole plus tobramycin. The duration of antibiotic therapy was not correlated with the reduction in infection rate. Thus, they concluded that, for severely contaminated wounds, broadspectrum antibiotics should be administered as soon as possible after injury and be continued for no more than 72 hours.^[19]

Other investigators have relied on wound cultures to direct antibiotic therapy. In a prospective study of open fractures, Robinson et al. reported 83% of the initial cultures as being positive.^[20] More importantly, over 90% of the organisms identified in these cultures were sensitive to routine antibiotics (1st generation cephalosporins). Four patients had persistent positive cultures at the time of a second debridement 24 hours after admission, and all developed a deep wound infection. They concluded that sequential wound cultures facilitated antibiotic therapy in the management of open extremity fractures. More recent investigations have shown no correlation of wound cultures at the time of presentation or obtained during the initial debridement and subsequent infection.^{[21] [22] [61]}

The importance of prophylactic antibiotics for open fractures of the knee, ankle, hand, digits, and skull has also been evaluated and found to be beneficial.^[23-33] Benson et al. compared clindamycin against cefazolin and saw no difference in the infection rates.^[34] This study suggested that any antimicrobial agent with Staphylococcus aureus coverage is adequate effective prophylaxis for open fractures. Thus, there is adequate Class I and II data to document the benefit of prophylactic antibiotics in open extremity fractures. Agents effective against Staphylococcus aureus would appear to be adequate for Grade I and II fractures.^{[1] [14] [34-38]} Since various gram negative organisms are cultured from Grade III wounds after the initial debridement, broader gram negative coverage through the addition of an aminoglycoside is beneficial.^{[17-20] [26] [39-53]}

C. Duration of therapy

Multiple studies have demonstrated the interaction between antibiotic therapy and wound management.^{[1] [17-20] [39] [42] [44] [45] [53-62]} When Grade I or II wounds are closed primarily, an additional 24 hours of antibiotic coverage is adequate independent of time of initiation after injury.^{[19] [37] [39] [42] [44] [45] [63]} Dellinger et al. observed no relationship between the duration of antibiotic administration (1 day versus 5 days) and the risk of infection, independent of the grade of the fracture.^{[8] [63]} Other reports have identified tibial fracture as being the most significant predictor of subsequent infection.^{[2] [6] [19] [63]}

D. Route of antibiotic delivery 

Most studies report discussed above use intravenous antibiotics for prophylaxis. An alternative technique, the antibiotic bead pouch, was developed in the late 1980’s . Several investigators have utilized aminoglycoside-polymethyl methacrylate (PMMA) beads alone or in addition to parenteral antimicrobials. It has been reported in several series as being useful in the management of traumatic open wounds associated with fracture,^{[57] [68]} particularly in cases of Gustilo types IIIB and IIIC injuries with acute infection and types II and IIIB with chronic osteomyelitis (3.7% versus 12%).^{[56] [69]} This technique promotes high local tissue levels of antibiotic concentration in the target area with a significantly decreased risk of potentially toxic systemic effects as seen with high dose parenteral delivery. In the acute setting, PMMA beads, which have been impregnated with an aminoglycoside antibiotic, are used in conjunction with 5 days of tradition systemic tobramycin, cefazolin and penicillin prophylaxis.^[67] This is combined with a regimen of thorough, serial wound debridements every 48 to 72 hours and bead exchanges with sterile self-adherent porous polyethylene drapes used to seal the wound. Systemic aminoglycoside levels are monitored with “peak” and “trough” levels with the doses being adjusted to maintain a therapeutic range. Soft tissue coverage techniques are carried out based on the immediate needs of the injury, and can include delayed primary closure, split-thickness skin grafting, local flaps or free-tissue transfers, as warranted. Skeletal stabilization is generally managed with intramedullary nailing or external fixation, the latter sometimes being converted to an intramedullary nail after soft tissue coverage has been achieved.^[64] The determinants of wound closure/soft tissue coverage include the viability of the local soft tissue envelope after adequate time for demarcation has been allowed, but generally should be done in under 10 days.^[66] It is not clear whether local therapy provides adequate tissue levels of antibiotic without systemic administration.

E. Evidentiary table

The evidentiary table contains 54 articles that were utilized to formulate these guidelines. The data are listed alphabetically by Class and include 10 Class I articles, 8 Class II, and 36 Class III references. The following data were retrieved and recorded from each article and are listed under the conclusion sections: (1) protocol design; (2) antibiotics utilized; (3) infectious complications; and (4) conclusions.

V. Summary

Multiple studies have documented the reduction in wound infections with the use of prophylactic antibiotics in the care of patients with open fractures. Although studies with various therapeutic agents have suggested an improved outcome with prolonged (> 24 hours) therapy, none have been done with appropriate controls. The most difficult open fracture wound to care for is the Grade IIIb tibial fracture. Although some authors advocate application of antibiotic impregnated beads for local control of infection in addition to parenteral administration, supportive Class I and II data are not available. These wounds (type III) should receive coverage for gram negative organisms in addition to gram positive coverage.

VI. Future investigations

There is a need to re-evaluate the current infection rate for long bone open fractures. Studies should specifically focus on high-risk injuries, ie. the Grade IIIb tibial injury. The study design should evaluate the effect of wound debridement, systemic and local antibiotics, duration, and specific agents as well as cost analysis. Because of the relatively low rate of infection, a multiinstitutional effort would allow a meaningful study to be completed in a short time period.

VII. References

1. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg 1976;58A:453-458.
2. 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;24:742-746.
3. Brumback RJ, Jones AL. Interobserver agreement in the classification of open fractures of the tibia. J Bone Joint Surg 1994;76-A:1162-1291.
4. Seligson D, Banis J, Metheny L. Tibia terrible. In: Coombs R, Green S, Sarmiento AS (Eds.) External Fixation and Functional Bracing. London: Orthotext, 1989:281-284.
5. Court-Brown CM. Antibiotic prophylaxis in orthopaedic surgery. Scand J Infect Dis Suppl 1990;70:74-79.
6. Dellinger EP, Miller SD, Wertz MJ, Grypma M, Droppert B, Anderson PA. Risk of infection after open fracture of the arm or leg. Arch Surg 1988;123:1320-1327.
7. Norden CW. A critical review of antibiotic prophylaxis and orthopedic surgery. Rev Infect Dis 1983;5:928-932.
8. Dellinger EP. Antibiotic prophylaxis in trauma: penetrating abdominal injuries and open fractures. Rev Infect Dis 1991;13:S847-857.
9. Oxman AD, Sackett DL, Guyatt GH. Users’ guide to the medical literature. I. How to get started. The Evidence-Based Medicine Working Group. JAMA 1993;270:2093-2095.
10. Cruse P. Wound infections. In Howard R, Simmons R (Eds.) Epidemiology and Clinical Characteristics in Surgical Infectious Diseases. Norwalk, CT: Appleton and Lange, 1988:319-329.
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12. Truetta J. War surgeries of extremities: treatment of war wounds and fractures. Brit Med J
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14. Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg 1974;56A:532-541.
15. Hansraj KK, Weaver LD, Todd AO, et al. Efficacy of ceftriaxone versus cefazolin in the prophylactic management of extra-articular cortical violation of bone due to low-velocity gunshot wounds. Orthop Clin North Am 1995;26:9-17.
16. Victoroff BN, Robertson WW Jr, Eichelberger MR, Wright C. Extremity gunshot injuries treated in an urban children’s hospital. Pediatr Emerg Care 1994;10:1-5.
17. Hope PG, Cole WG. Open fractures of the tibia in children. J Bone Joint Surg 1992;74B:546-553.
18. Buckley SL, Smith GR, Sponseller PD, Thompson JD, Robertson WW Jr, Griffin PP. Severe
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19. Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop 1989;243:36-40.
20. Robinson D, On E, Hadas N, Halperin N, Hofman S, Boldur I. Microbiologic flora contaminating open fractures: Its significance in the choice of primary antibiotic agents and the likelihood of deep wound infection. J Orthop Trauma 1989;3:283-286.
21. Chapman MW. Open Fractures. In: Chapman MW, (ed.). Operative Orthopaedics. 2nd Edition. Philadelphia: JB Lippincott Company 1993:365-372.
22. Lee J. Efficacy of cultures in the management of open fractures. Clin Orthop1997;339:71-75.
23. Torchia ME, Lewallen DG. Open fractures of the patella. J Orthop Trauma 1996;10:403-409.
24. Acello AN, Wallace GF, Pachuda NM. Treatment of open fractures of the foot and ankle: A preliminary report. J Foot Ankle Surg 1995;34:329-346.
25. Marsh JL, Saltzman CL, Iverson M, Shapiro DS. Major open injuries of the talus. J Orthop Trauma 1995;9:371-376.
26. Sanders R, Pappas J, Mast J, Helfet D. The salvage of open grade IIIb ankle and talus fractures. J Orthop Trauma 1992;6:201-208.
27. Suprock MD, Hood JM, Lubahn JD. Role of antibiotics in open fractures of the finger. J Hand Surg 1990;15A:761-764.
28. Peacock KC, Hanna DP, Kirkpatrick K, Breidenbach WC, Lister GD, Firrell J. Efficacy of perioperative cefamandole with postoperative cephalexin in the primary outpatient treatment of open wounds of the hand. J Hand Surg 1988;13A:960-964.
29. Sloan JP, Dove AF, Maheson M, Cope AN, Welsh KR. Antibiotics in open fractures of the distal phalanx. J Hand Surg 1987;12B:123-124.
30. Franklin JL, Johnson KD, Hansen ST Jr. Immediate internal fixation of open ankle fractures.
    Report of thirty-eight cases treated with a standard protocol. J Bone Joint Surg 1984;66A:1349-1356.
31. Rosenwasser RH, Delgado TE, Buchheit WA. Compound frontobasal skull fractures:
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32. Mendelow AD, Campbell D, Tsementzis SA, et al. Prophylactic antimicrobial management of
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33. Pinckney LE, Currarino G, Kennedy LA. The stubbed great toe: A cause of occult compound fracture and infection. Radiology 1981;138:375-377.
34. Benson DR, Riggins RS, Lawrence RM, Hoeprich PD, Huston AC, Harrison JA. Treatment of open fractures: A prospective study. J Trauma 1983;23:25-30.
35. Wisniewski TF, Radziejowski MJ. Gunshot fractures of the humeral shaft treated with external fixation. J Orthop Trauma 1996;10:273-278.
36. Johnson KD, Johnston DW. Orthopedic experience with methicillin-resistant Staphylococcus aureus during a hospital epidemic. Clin Orthop 1986;212:281-288.
37. Bergman BR. Antibiotic prophylaxis in open and closed fractures: A controlled trial. Acta
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38. Kennedy T, Premer RF, Lagaard S, Gustilo RB. Management of tibial fractures. Minn Med
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39. Cullen MC, Roy DR, Crawford AH, Assenmacher J, Levy MS, Wen D. Open fracture of the
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40. Grimard G, Naudie D, Laberge LC, Hamdy RC. Open fractures of the tibia in children. Clin Orthop 1996;332:62-70.
41. Song KM, Sangeorzan B, Benirschke S, Browne R. Open fractures of the tibia in children. J
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42. Cole JD, Ansel LJ, Schwartzberg R. A sequential protocol for management of severe open tibial fractures. Clin Orthop 1995;315:84-103.
43. Kreder HJ, Armstrong P. A review of open tibia fractures in children. J Pediatr Orthop
    1995;15:482-488.
44. Bednar DA, Parikh J. Effect of time delay from injury to primary management on the incidence of deep infection after open fractures of the lower extremities caused by blunt trauma in adults. J Orthop Trauma 1993;7:532-535.
45. Buckley SL, Smith G, Sponseller PD, Thompson JD, Griffin PP. Open fractures of the tibia in children. J Bone Joint Surg 1990;72A:1462-1469.
46. Swiontkowski MF. Criteria for bone debridement in massive lower limb trauma. Clin Orthop 1989;243:41-47.
47. Burgess AR, Poka A, Brumback RJ, Flagle CL, Loeb PE, Ebraheim NA. Pedestrian tibial
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48. Gustilo RB, Gruninger RP, Davis T. Classification of type III (severe) open fractures relative
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49. Patzakis MJ, Wilkins J, Moore TM. Use of antibiotics in open tibial fractures. Clin Orthop
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50. Patzakis MJ, Wilkins J, Moore TM. Considerations in reducing the infection rate in open tibial fractures. Clin Orthop 1983;178:36-41.
51. Christensen J, Greiff J, Rosendahl S. Fractures of the shaft of the tibia treated with AOcompression osteosynthesis. Injury 1982;13:307-314.
52. Gustilo RB. Use of antimicrobials in the management of open fractures. Arch Surg 1979;114:805-808.
53. Clancey GJ, Hansen ST Jr. Open fractures of the tibia: A review of one hundred and two cases. J Bone Joint Surg 1978;60B:118-122.
54. Steiner AK, Kotisso B. Open fractures and internal fixation in a major African hospital. Injury 1996;27:625-630.
55. Geissler WB, Powell TE, Blickenstaff KR, Savoie FH. Compression plating of acute femoral shaft fractures. Orthopedics 1995;18:655-660.
56. Ostermann PAW, Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085 consecutive cases. J Bone Joint Surg 1995;77B:93-97.
57. Ostermann PAW, Henry SL, Seligson D. The role of local antibiotic therapy in the management of compound fractures. Clin Orthop 1993;295:102-111.
58. Hoffer MM, Johnson B. Shrapnel wounds in children. J Bone Joint Surg 1992;74A:766-769. 59.
59. Kaltenecker G, Wruhs O, Quaicoe S. Lower infection rate after interlocking nailing in open fractures of femur and tibia. J Trauma 1990;30:474-479.
60. Russell GG, Henderson R, Arnett G. Primary or delayed closure for open tibial fractures. J Bone Joint Surg 1990;72B:125-128.
61. Merritt K. Factors increasing the risk of infection in patients with open fractures. J Trauma 1988;28:823-827.
62. Wilson NI. A survey, in Scotland, of measures to prevent infection following orthopaedic surgery. J Hosp Infect 1987;9:235-242.
63. Dellinger EP, Caplan ES, Weaver LD, et al. Duration of preventive antibiotic administration for open extremity fractures. Arch Surg 1988;123:333-339.
64. Keating JF, Blachut PA, O’Brien PJ, Meek RN, Broekhuyse HM. Reamed nailing of open tibial fractures: Does the antibiotic bead pouch reduce the deep infection rate? J Orthop Trauma 1996;10:298-303.
65. Sangha KS, Miyagawa CI, Healy DP, Bjornson HS. Pharmacokinetics of once-daily dosing of gentamicin in surgical intensive care unit patients with open fractures. Ann Pharmacother 1995;29:117-119.
66. Ostermann PA, Henry SL, Seligson D. Timing of wound closure in severe compound fractures. Orthopedics 1994;17:397-399.
67. Seligson D, Ostermann PA, Henry SL, Wolley T. The management of open fractures associated with arterial injury requiring vascular repair. J Trauma 1994;37:938-940.
68. Henry SL, Ostermann PA, Seligson D. The antibiotic bead pouch technique. The management of severe compound fractures. Clin Orthop 1993;295:54-62.
69. Henry SL, Ostermann PA, Seligson D. The prophylactic use of antibiotic impregnated beads in open fractures. J Trauma 1990;30:1231-1238.

Table

(R) – Review article