Case Reports in Orthopedics

Volume 2013 (2013), Article ID 942076, 9 pages

http://dx.doi.org/10.1155/2013/942076

Case Report

Gas Gangrene in Orthopaedic Patients

Zhimin Ying,¹ Min Zhang,² Shigui Yan,¹ and Zhong Zhu³

¹Department of Orthopaedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jiefang Road, Hangzhou, Zhejiang 317000, China

²Taizhou Hospital of Zhejiang Province, The Forth Affiliated Hospital of Wenzhou Medical University, No. 150 Ximen Road, Linhai, Zhejiang 317000, China

³Department of Orthopaedic Surgery, Taizhou Hospital of Zhejiang Province, The Forth Affiliated Hospital of Wenzhou Medical University, No. 150 Ximen Road, Linhai, Zhejiang 317000, China

Received 13 August 2013; Accepted 9 September 2013

Academic Editors: I.-H. Choi, A. Ramasamy, and H. G. Said

Copyright © 2013 Zhimin Ying et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Clostridial myonecrosis is most often seen in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. Since 1953 cases of gas gangrene have been reported in orthopaedic patients including open fractures, closed fractures, and orthopaedic surgeries. We present a case of 55-year-old obese woman who developed rapidly progressive gas gangrene in her right leg accompanied by tibial plateau fracture without skin lacerations. She was diagnosed with clostridial myonecrosis and above-the-knee amputation was carried out. This patient made full recovery within three weeks of the initial episode. We identified a total of 50 cases of gas gangrene in orthopaedic patients. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and outcome. Based on our case report and the literature review, emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation.

1. Introduction

Emergency physicians and surgeons are confronted with patients of gas gangrene so uncommon in civilian practice that many are unfamiliar with its signs and symptoms and do not recognize its development quickly and accurately. The difficulties in diagnosis not only lie in unfamiliarity with the signs and symptoms of gas gangrene but also in the lack of differentiation between contamination and infection and to the confusion between gas gangrene and various clostridial infections and other bacterial and nonbacterial lesions simulating gas gangrene [1, 2]. Gas gangrene occurs in a variety of clinical settings that can be subdivided into three major types: posttraumatic origins, postoperative origins, and spontaneous occurrences. Clostridial myonecrosis, also known as true gas gangrene, is the most devastating kind of clostridial infection which requires aggressive, early surgical management. Its onset is insidious and subsequent progressive rapidly. Spontaneous types occurred in patients with compromised medical conditions including uncontrolled diabetes mellitus and various forms of malignancy, the more commonly reported being leukemia and breast cancer [3]. Clostridium septicum is the major cause of nontraumatic spontaneous gas gangrene in patients with immunosuppressant diseases [4].

2. Case Report

A 55-year-old female obese farmer (BMI 35) presented to the Emergency Department with a two-day history of the right leg progressing sensory deprivation and swelling. Eight days ago she had a car accident which caused her right tibial plateau fracture. Two days after her hospitalization, elective surgery for the fracture was performed at a local hospital. Afterwards, the patient felt increasing pain out of proportion to physical findings accompanied by progressive swelling, numbness, and weakness of the limb. She was unable to move her right lower extremity and had no sensation below the knee joint level. These signs were not taken seriously. Then she was transferred to our university hospital with the presumptive diagnosis of gas gangrene. She denied chills, anorexia, or other symptoms. She also reported no previous episodes or other recent illnesses. Previous medical history included mild type 2 diabetes mellitus which lasted over 20 years poorly controlled with metformin and hypertension treated with hydrochlorothiazide. She was not taking any other medications.

On physical examination this patient was febrile, alert, and comfortable; vital signs were temperature of 38.2 degrees centigrade, pulse of 110 beats/min, respiratory rate of 18 breaths/min, and blood pressure of 105/57 mmHg. Head, neck, cardiac, lung, and abdominal examinations were unremarkable. The physical examination revealed severe swollen and brownish skin of the limb with bullae exuding from the incision (Figure 1). Subcutaneous crepitus extended along the length of the limb and the skin discoloration spread from knee to ankle. Roentgenograms revealed gas in the interfacial planes of the leg. Extensive gas formation throughout all the muscle compartments of the right leg reaching to the level of knee joint was present. Laboratory evaluation showed that white blood cell count was 22.2 × 10⁹/L, hemoglobin was 83 g/L, platelet count was 183 × 10⁹/L, a serum glucose of 324 mg/dL, C-reactive protein was 48.0 mg/dL, and serum creatinine was 155 μmol/L. Examination of a needle aspirated from the incision showed gram-positive bacilli.

Figure 1: The limb was severe swollen and skin was brownish with bullae exuding from the incision.

A diagnosis of gas gangrene was made and the patient was started on broad spectrum antibiotic coverage with intravenous penicillin, clindamycin, metronidazole, and fluid resuscitation. Urgent surgery was carried out immediately. Upon incision, the musculature was found to be extensive necrotic, foul smelling, and crepitant (Figure 2). An above-the-knee amputation remained the single best life-saving treatment and was performed, followed by extensive debridement of the remaining necrotic tissue. Then she was sent to the adult intensive care unit and all the wounds were kept open postoperatively. Two days later, the patient was taken to the operating room again for wound exploration. At this time, the muscle and tissue were found to be viable without evidence of spreading infection, and the wound was closed in a standard fashion. Hemocultures and intraoperative cultures both confirmed the presence of C. perfringens. With aggressive surgical and medical management, this patient made a full recovery and was subsequently discharged twenty days after his initial presentation.

Figure 2: The muscle was found to be necrotic, foul smelling, and crepitant both superficially and deep.

3. Reviw of Published Gas Gangrene in Orthopaedic Patients

All published, English language and full-text available, Medline-reported orthopaedic patients with gas gangrene were included in this review. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and clinical outcome. As seen in Table 1, we identified a total of 50 cases of gas gangrene in orthopaedic patients. Of these, 24(48%) cases were caused by C. perfringens. Average age is 28.75 years old (range from 5 to 76).

Table 1: Gas gangrene infections in traumatic orthopaedic patients.

Source
Cause
Age
Fracture
Soft tissue
Pathogen
Outcome

Fee, 1977 [5]
Fall from a tree
8
Closed, forearm
A small laceration
Gram-positive Spore-forming rods
Lived with disarticulation

Fall from a tree
10
Open, right forearm
Two small lacerations
Clostridium perfringens
Lived with amputation

Fall from a tree
11
Open, right forearm
A puncture wound
Clostridium perfringens
Lived with amputation

Fall from a roof
12
Open, right forearm
Two openings
Clostridium perfringens
Lived with preserved forearm

Fall on the street
52
Open, left radius
A puncture wound
Gram-positive rods
Lived with amputation

Buchanan and Gordon, 1980 [6]
Fall from 5 stories
19
Compound fracture of right tibia and fibula
Contaminated with dirt, gravel
Clostridium perfringens
Lived with amputation

Fulford, 1969 [7]
Traffic accident
19
Open, right femur
Contaminated, No detail
Unknown
Lived with preserved limb

Lucas et al., 1976 [8]
Kicked on right shin in a tackle
24
Tibia and fibula
7 cm wound
Clostridium septicurn
Lived with preserved limb

Woolley et al., 2004 [9]
Fall from high place
39
Open, left tibia, and fibula
Gustillo Grade III
Clostridium septicurn (no gas gangrene)
Lived with preserved limb

Werry and Meek, 1986 [10]
Unknown
32
Distal radius
Abrasion of the volar wrist skin
Clostridium perfringens
Lived with amputation

Goon et al., 2005 [11]
Local accident
76
No fracture
No traumatic history
Clostridium septicurn
Died

Taylor et al., 2011 [12]
High-speed motor vehicle collision
21
Closed, right femur with traction pin
Multiple organ injuries
Clostridium perfringens
Died

Mulier et al., 1993 [13]
Fall from a height of 8 feet
45
Closed, femoral fracture
Unknown
Clostridium septicurn
Survived with disarticulation

Lorea et al., 2004 [14]
Muscle transfer for opponensplasty
49
No fracture
Normal muscle surgery
Clostridium perfringens, Sordellii
Survived with preserved forearm

Sevitt, 1953 [15]
Playing football
26
Closed, left ankle
Unknown
Clostridium perfringens
Survived with amputation

HILL, 1959 [16]
Fall from a gate
6
Left forearm fracture
A small wound on the forearm
Unknown
Survived with amputation

Aufranc et al., 1969 [17]
Struck by a rotating truck wheel
29
Open, right tibia
Wringer-type injury of leg.
Presence of gram-positive rods
Survived with preserved limb

Automobile accident
13
Compound, left tibia, and fibula
Unknown
Bacilli welchii
Died

Fall from window to ground
24
Compound, left tibia
Unknown
Bacilli welchii
Survived with amputation

Automobile accident
37
Compound, left tibia, and fibula
Unknown
Bacilli welchii
Died

Hooked by a cow
6
Compound, right forearm
Unknown
Bacilli welchii
Survived with amputation

Boland, 1929 [18]
Street accident
52
Compound, left tibia, and fibula
Unknown
Positive culture, detail Unknown
Survived with amputation

Truck Accident
21
Compound, left tibia, and fibula
Unknown
Positive culture, detail Unknown
Survived with preserved limb

Motorcycle accident
18
Compound, right tibia, and fibula
Unknown
Bacilli welchii
Survived with amputation

Struck by a truck
5
Compound, upper extremity, left femur, left tibia, and fibula
Unknown
Bacilli welchii
Died

Street-car accident
13
Compound, both legs
Unknown
Bacilli welchii
Died

Knee joint fracture from gun-shot
30
Knee joint fracture
Unknown
Positive culture, detail Unknown
Survived with amputation

Auto accident
36
Compound, right tibia, and fibula
Unknown
Positive culture, detail Unknown
Survived with amputation

Falling from freight train
16
Compound, both legs
Unknown
Positive culture, detail Unknown
Survived with amputation

Motorcycle accident
40
Compound, left tibia, and fibula
Unknown
Positive culture, detail Unknown
Survived with preserved limb

Automobile accident
25
Compound, both legs
Unknown
Positive culture, detail Unknown
Died

Gun-shot
20
Compound, right ulnar, and radius
Unknown
Negative culture
Died

Brume and Ijagha, 1985 [19]
Unknown
9
Closed Colles’ Fracture
Unknown
Unknown
Survived with amputation

Unknown
27
Closed, medical malleolus
Unknown
Unknown
Survived with amputation

Unknown
30
Closed,tibia and fibula
Unknown
Unknown
Died

Unknown
14
Closed Colles’ Fracture
Unknown
Unknown
Survived with amputation

Moehring, 1988 [20]
Automobile accident
13
Right ankle region
Marked soft tissue swelling
Clostridium perfringens
Lived with preserved limb

Oncel and Arsoy, 2010 [21]
Nail pierced the skin of hand
16
No fracture
A small wound on the hand
Gram-positive rods
Survived with amputation

Hoffman et al., 1971 [22]
Working accident
25
Tibia fracture
Muscle and skin lacerated
Clostridium welchii
Survived

DeHaven and Evarts, 1971 [23]
Fall from horseback
10
Open, both bones of forearms
Mild damage of soft tissue
Clostridium perfringens
Survived with amputation

Automobile accident
44
Open, Bilateral tibia, and fibulae
Damaged and contaminated severely
Pseudomonas, Klebsiella et al.
Survived with amputation

Automobile accident
21
Open, pelvic
Multiple
Clostridium perfringens
Survived

Fall from running
10
Open, both bones of forearms
Mild damage of soft tissue
Clostridium perfringens
Survived with amputation

Automobile accident
19
Open, tibia, and fibula
Severe damage of soft tissue
Bacillus subtilis, Proteus
Survived with amputation

Johnson et al., 1994 [24]
Arthroscopic knee surgery
36
No fracture
No
Clostridium Septicum
Survived with amputation

Hip Arthroplasty
57
No fracture
No
Clostridium Septicum
Survived

Dykes, 1977 [25]
Hip nailing
71
Transcervical fracture of femur
No
Clostridium welchii
Died

Hip nailing and plate fixation
68
Subtrochanteric fracture of femur
No
Unknown
Died

Hip nailing
79
Transcervical fracture of femur
No
Unknown
Died

Miller et al., 1993 [26]
Iliac crest bone graft transplantation
55
Nonunion of closed fracture of clavicle
No
Clostridium perfringens
Survived

(1) Compound fracture indicates open fracture, while simple fracture means closed fracture.

(2) Bacillus welchii is another expression of Clostridium perfringens.

(3) Clostridium perfringens (formerly known as C. welchii).

In our review of published orthopaedic gas gangrene literature, we found that conditions related with gas gangrene in orthopaedic patients can be grouped into three major categories: infection with clostridial myonecrosis, nonclostridial myonecrosis, unidentified; 38 patients survived, of which 25 survived with amputation, while 12 patients died. Gas gangrene followed by simple fracture occurred in 25 patients; 3 cases presented with gas gangrene after elective orthopaedic surgery and the rest cases were resulted from compound fracture. As for fracture location, most gas gangrene cases were involved with tibia and/or fibula fracture while forearm fractures ware ranked in the second place and following were femur, ankle, knee, and pelvic. Especially 5 patients developed gas gangrene with no fractures (three were selective orthopaedic surgeries, one was nail piercing, and the other one was soft tissue injury (see Table 2)).

Table 2: Clinical outcome, pathogens, fractures locations, fractures, or surgeries types.

(a) Clinical outcome after infection with gas gangrene

Outcome
Survived with amputation
Survived with no amputation
Died

Number
25
13
12

(b) Pathogen of gas gangrene accompanied with traumatic orthopaedic patients

Pathogen
Clostridium myonecrosis
Non-clostridial myonecrosis
Unidentified

Number
28
3
19

Clostridium myonecrosis including Clostridium perfringen and septium while nonclostridial myonecrosis including culture negative; unidentified indicates no detail about the infection pathogen were reported.

(c) Fractures locations together with gas gangrene

Location
Tibia and/or fibula
Forearm
Femur
Ankle
Clavicle
Knee
Pelvic
None

Number
21
14
7
2
1
1
1
S

One case involved multiple locations of fractures: forearm, tibia and fibula, and femur; forearm including both or single bones of the forearm.

(d) Fractures or surgeries types associated with gas gangrene

Fracture severity
Simple fracture
Compound fracture
Elective orthopaedic surgery

Number
25
22
3

Compound (open) fracture: the bone breaks and pieces of the bone go through the internal soft tissue of the body and break through the skin from the inside.

4. Discussion

Gas gangrene is generally regarded as a disease associated with war or other mass casualty situations and is seldom a feature of normal peaceful time medical practice. The cause of gas gangrene could be grouped into following different types: clostridial myonecrosis, clostridial cellulitis, nonclostridial lesion simulation gas gangrene. Clostridial myonecrosis is the preferred term to denote the clinical syndrome of true gas gangrene [27]. More than 90% of these lesions occur in the extremities, thigh, shoulder, and so on. Clostridial cellulitis has been confused with clostridial myonecrosis by clinicians. Clostridial cellulitis has been noted to be a septic crepitant process involving epifascial, retroperitoneal, or other connective tissues, and its onset has been generally more gradual than clostridial myonecrosis. It is usually little pain, no edema, and little systemic toxicity. The wound is foul with brownish seropurulent exudates, and gas is found diffused through the tissues and bubbling up in the wound. The gas is much more evident than in clostridial myonecrosis, but it has never been found to be intramuscular. Also a large number of other bacterial and nonbacterial lesions which resemble clostridial myonecrosis may be seen in routine clinical practice. Many of these are diagnosed as gas gangrene and diagnostic skill knowledge is necessary for their differentiation [28]. For example, Streptococcal myonecrosis, which clinically resemble a subacute form of clostridial myonecrosis, is the second variety of anaerobic myonecrosis. Clinical considerations are listed in Table 3 when gas gangrene present.

Table 3: Clinical consideration when gas gangrene is present.

(I) Clostridial myonecrosis (true gas gangrene)

 (A) Localized: crepitant or noncrepitant

 (B) Diffuse: crepitant or noncrepitant together with toxemia

(II) Clostridial cellulitis: anaerobic or crepitant

(III) Nonclostridial

 (A) Bacterial: aerobic aerogenic infections; Staphylococcal

 fasciitis; anaerobic streptococcal infections

 (B) Nonbacterial: mechanical trauma; infiltration from air-hose

 injury

The most common causative organism of clostridial myonecrosis is C. perfringens while C. septicum is considered as the second most frequent agent. C. perfringens is commonly found in the human gastrointestinal tract, including the oral cavity. Myonecrosis resulting from C. perfringens alone after surgical procedures is rather uncommon. Clostridium myonecrosis following orthopaedic surgery is associated with a definite set of conditions: underlying malignancies, hematological and gastrointestinal solid tumors primarily, diabetes mellitus and atherosclerotic disease, and severe peripheral vascular disease [29].

Gas gangrene is an acute and life threatening infection characterized by fever, sudden onset of prominent pain, massive local edema, severe extensive myonecrosis, and the accumulation of gas at the site of infection. The typical manifestation of this disease usually starts with excruciating pain, out of proportion to physical findings, not relieved by pain killers. As the infection progresses, myonecrosis is accompanied by necrotizing fasciitis and cutaneous and muscle necrosis. The appearance of the skin around the site of infection usually becomes tense and changes from pale to bronze initially and then to purplish red, and multiple hemorrhagic bullae develop. Paramount to successful treatment for gas gangrene involves prompt recognition of the diagnosis and initiation multiple therapy including supportive measures, antimicrobial therapy, and timely surgical intervention. Despite this, in many cases of C. perfringens induced gas gangrene, radical amputation still remains the treatment of best choice [30]. If not controlled, it will always result in systemic toxemia, hypotension, shock, multiorgan failure, and death [31]. Hyperbaric oxygen therapy is recommended by some experts but is controversial because its effectiveness has not yet been established.

Still we cannot identify the definitive cause of the clostridial myonecrosis in our case, as both postoperative origins and spontaneously occurrences could be possible. Our case is unique in two aspects. First, as we all know, the responsible organism C. perfringens is mostly associated with development of traumatic gas gangrene but also can be associated with the nontraumatic spontaneous gas gangrene in patients with immunocompromised condition including malignancies and diabetes mellitus [2, 32]. Impaired evacuation and motility of the stomach (and the small intestine) has been described in diabetics with long lasting unsatisfactory diabetes compensation, microangiopathic complications, and diabetic autonomous neuropathy [33]. Postoperative infection of elective surgical wounds with Clostridium species has been linked to gastrointestinal tract lesions. As clostridia can multiply readily in low-oxygen conditions, infections are usually seen in the setting of decreased intestine lining blood supply which could account for a route of entry for hematogenous spread. Second, gas gangrene rarely occurs in the patients undergoing elective surgery. One of the basic principles of orthopedic surgery is that gas gangrene does not develop in closed fractures. Almost all cases of gas gangrene after orthopaedic surgery developed in open wounds which was not adequately debrided, in association with peripheral vascular disease and immunocompromised status. Even patients with closed fracture clostridium gas gangrene also had been found [11]. In our case, a possible mechanism is soil contamination of the skin near or at the infection site, as well as the severe injured soft tissue around the fracture together that contribute to the production histohypoxia environment. All these factors such as immunocompromised status, unviability of tissues, and local decrease of blood supply together nourished the gas gangrene. But the exact origin of the germ remains unknown.

5. Conclusion

Based on the case presented in the paper and our review of the literature on gas gangrene in orthopaedics patients, several following points should be emphasized.

(1)Our emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation. Gas gangrene, while rare in now peace days, can be a devastating complication of almost any small wound or surgical procedure even one as common as closed reduction of fractures. It is our experience that we should give sufficient extension of the wound to provide adequate visualization of surgical field so as to be certain that all the necrotic or foreign material has been removed. (2)Strict aseptic techniques should be observed for even the most minor procedure. Clostridial spores are ubiquitous and can reside in hospital environments, possibly on surgeons’ hands, patients’ skin, topical application, and so on. (3)The best way to prevent gas gangrene is meticulous wound debridement and delayed closure for all potentially contaminated wounds regardless of closed or open fractures. (4)Once gas gangrene is diagnosed, careful and adequate debridement should be instituted immediately to avoid further deterioration excision of necrotic tissue still the cornerstone of treatment, which should be involved with antibiotics and all other supportive treatments.(5)Systematic resuscitative efforts should be instituted immediately in whom the diagnosis of incipient gas gangrene is even considered. This cannot be overemphasized.(6)Recognized that gas gangrene may occur spontaneously and often in a immunocompromised patient, postoperative wounds may also develop gas gangrene due to the local soft tissue damage and decreasing blood supply.

Consent

Written informed consent was obtained from the patient for publication of this case report.

Conflict of Interests

The authors have no conflict of interests to declare.

References

W. A. Altemeier, W. R. Culbertson, M. Vetto, and W. Cole, “Problems in the diagnosis and treatment of gas gangrene,” A.M.A. Archives of Surgery, vol. 74, no. 6, pp. 839–845, 1957.

W. A. Altemeier, “Diagnosis classification and general management of gas producing infections, particularly those produced by Clostridium Perfringens,” in proceedings of the 3rd International Conference on Hyperbaric Medicine, pp. 481–490, National Academy of Sciences, Washington, DC, USA, 1966.

R. S. Rich and R. F. Salluzzo, “Spontaneous clostridial myonecrosis with abdominal involvement in a nonimmunocompromised patient,” Annals of Emergency Medicine, vol. 22, no. 9, pp. 1477–1480, 1993.

H. Shibuya, H. Terashi, S. Kurata et al., “Gas gangrene following sacral pressure sores,” Journal of Dermatology, vol. 21, no. 7, pp. 518–523, 1994.

N. F. Fee, A. Dobranski, and R. S. Bisla, “Gas gangrene complicating open forearm fractures. Report of 5 cases,” Journal of Bone and Joint Surgery A, vol. 59, no. 1, pp. 135–138, 1977.

J. R. Buchanan and S. L. Gordon, “Gas gangrene in a wound treated without skin closure: a case report,” Clinical Orthopaedics and Related Research, vol. 148, pp. 233–236, 1980.

P. C. Fulford, “Gas gangrene following compound fracture of femur,” Proceedings of the Royal Society of Medicine, vol. 62, no. 7, p. 644, 1969.

H. K. Lucas, D. C. E. Speller, and M. Stephens, “Chronic Clostridium septicum infection of a tibal fracture: a case report,” Injury, vol. 8, no. 2, pp. 117–119, 1976.

I. J. Woolley, R. L. Love, and A. C. Street, “Clostridium septicum bacteremia without gas gangrene as a late consequence of a contaminated wound,” Surgical Infections, vol. 5, no. 3, pp. 315–317, 2004.

D. G. Werry and R. N. Meek, “Clostridial gas gangrene complicating Colles' fracture,” Journal of Trauma, vol. 26, no. 3, pp. 280–283, 1986.

P. K. Y. Goon, M. O'Brien, and O. G. Titley, “Spontaneous Clostridium septicum septic arthritis of the shoulder and gas gangrene: a case report,” Journal of Bone and Joint Surgery A, vol. 87, no. 4, pp. 874–877, 2005.

B. C. Taylor, T. J. Bramwell, and N. Formaini, “Gas gangrene as a result of femoral traction pin placement,” Case Reports in Orthopedics, vol. 2011, Article ID 459812, 3 pages, 2011.

T. Mulier, M. Morgan, and G. Fabry, “Clostridium septicum gangrene complicating a closed femoral fracture,” Acta Orthopaedica Belgica, vol. 59, no. 4, pp. 416–419, 1993.

P. Lorea, Y. Baeten, N. Chahidi, D. Franck, and J.-P. Moermans, “A severe complication of muscle transfer: clostridial myonecrosis,” Annales de Chirurgie Plastique et Esthetique, vol. 49, no. 1, pp. 32–35, 2004.

S. Sevitt, “Gas-gangrene infection in an operating-theatre,” The Lancet, vol. 262, no. 6796, pp. 1121–1123, 1953.

M. M. HILL, “Gas-gangrene following fracture,” The Lancet, vol. 1, no. 7075, pp. 729–730, 1959.

O. E. Aufranc, W. N. Jones, and B. E. Bierbaum, “Gas gangrene complicating fracture of the tibia,” Journal of the American Medical Association, vol. 209, no. 13, pp. 2045–2047, 1969.

F. K. Boland, “Gas gangrene in compound fractures,” Annals of Surgery, vol. 90, no. 4, pp. 603–613, 1929.

J. Brume and E. O. Ijagha, “Traditional bone setters and gas gangrene,” The Lancet, vol. 1, no. 8432, p. 813, 1985.

H. D. Moehring, “Postoperative clostridial infection. A case report,” Clinical Orthopaedics and Related Research, no. 228, pp. 265–269, 1988.

S. Oncel and E. S. Arsoy, “Rapidly developing gas gangrene due to a simple puncture wound,” Pediatric Emergency Care, vol. 26, no. 6, pp. 434–435.

S. Hoffman, J. F. Katz, and J. H. Jacobson, “Salvage of a lower limb after gas gangrene,” Bulletin of the New York Academy of Medicine, vol. 47, no. 1, pp. 40–49, 1971.

K. E. DeHaven and C. M. Evarts, “The continuing problem of gas gangrene: a review and report of illustrative cases,” Journal of Trauma, vol. 11, no. 12, pp. 983–991, 1971.

S. Johnson, M. R. Driks, R. K. Tweten et al., “Clinical courses of seven survivors of Clostridium septicum infection and their immunologic responses to α toxin,” Clinical Infectious Diseases, vol. 19, no. 4, pp. 761–764, 1994.

R. G. Dykes, “Gas gangrene after hip nailing,” Australian and New Zealand Journal of Surgery, vol. 47, no. 6, pp. 790–792, 1977.

S. D. Miller, B. R. Moed, and J. L. Chess, “Clostridium perfringens infection of an anterior iliac crest bone graft donor site: a case report,” Clinical Orthopaedics and Related Research, no. 293, pp. 265–268, 1993.

L. Weinstein and M. A. Barza, “Gas gangrene,” The New England Journal of Medicine, vol. 289, no. 21, pp. 1129–1131, 1973.

W. A. Altemeier and W. D. Fullen, “Prevention and treatment of gas gangrene,” Journal of the American Medical Association, vol. 217, no. 6, pp. 806–813, 1971.

D. A. Present, R. Meislin, and B. Shaffer, “Gas gangrene: a review,” Orthopaedic Review, vol. 19, no. 4, pp. 333–344, 1990.

D. L. Stevens and A. E. Bryant, “The role of clostridial toxins in the pathogenesis of gas gangrene,” Clinical Infectious Diseases, vol. 35, no. 1, pp. S93–S100, 2002.

D. L. Stevens, “The pathogenesis of clostridial myonecrosis,” International Journal of Medical Microbiology, vol. 290, no. 4-5, pp. 497–502, 2000.

J. M. Pereira De Godoy, J. Vasconcelos Ribeiro, and L. A. Caracanhas, “Mortality and diabetes mellitus in amputations of the lower limbs for gas gangrene: a case report,” International Journal of Lower Extremity Wounds, vol. 7, no. 4, pp. 239–240, 2008.

C. J. Nolan, P. Damm, and M. Prentki, “Type 2 diabetes across generations: from pathophysiology to prevention and management,” The Lancet, vol. 378, no. 9786, pp. 169–181, 2011.