Abstract
Background: Management of post-traumatic open fractures resulting from severe injuries of the lower extremity continues to challenge orthopedic and reconstructive surgeons. Moreover, post-traumatic osteoarticular infections due to Clostridium species are rare, with few reports in the literature. We describe possible pathomechanisms and propose treatment options for cases of delayed diagnosis of osteoarticular infections with Clostridium spp. Case Reports: Two patients sustained severe osteoarticular infection due to Clostridium spp. after open epi- and metaphyseal fractures of the lower extremity. In combination with radical debridement, ankle arthrodesis and long-term antibiotic treatment, satisfactory results were achieved after a follow-up of 18 months and 24 years. Conclusion: Clostridium species are difficult to identify, treatment is usually delayed and most patients have unfavourable outcomes.
Although Clostridium species can be found regularly in post-traumatic wounds, post-traumatic osteoarticular infection due to Clostridium is rare. Approximately 20 cases have been reported in patients with open fractures, located mainly in the diaphyseal area (1-4). Clostridium species are found most often in fractures with severe environmental contamination of the wound during trauma (5).
Clostridium species are anaerobic or occasionally aerotolerant gram-positive rods, found in soil, feces, sewage and marine sediments (6). They have the ability to form endospores, mainly under anaerobic conditions. These spores display high resistance to physical and chemical influences and are not sensitive to antibiotics. In addition, several Clostridium species have the ability to produce numerous protein toxins, causing necrotizing tissue destruction (7). Thus, bone marrow necrosis or necrotic bone fragments may occur (1, 8).
The laboratory diagnosis of clostridial diseases depends on proper collection and handling of tissue samples (6). However, diagnosis is complicated by the fact that bone and joint infections due to Clostridium species are often polymicrobial (2). Although identification can be time-consuming, complete identification and testing of antimicrobial sensitivities have to be pursued. Species other than C. perfringens display a high variability in sensitivity testing, including to penicillin, cephalosporins, carbapenems and clindamycin (9).
Once the strain has been identified, aggressive surgical treatment is mandatory (10). When in doubt, temporary or definitive external fixation should be preferred over internal fixation to allow repeated lavage if necessary (2). Wound excision and lavage without extensive bone tissue resection nearly always fails (2), probably due to persistence of spores in surrounding tissue. All the infected tissue must be excised and any internal fixation hardware removed (2).
As a rule of thumb, Clostridium spp. complicating diaphyseal fractures cause extended bone loss due to necrosis. Reconstruction requires time-consuming segmental bone reconstruction, frequently combined with soft tissue restoration. In this report, we present two patients diagnosed with open malleolar dislocation fractures of the distal lower leg with subsequent osteoarticular infection due to Clostridium spp. It is the purpose of this article to analyse whether the extent of damage is similar to that in diaphyseal fractures. Furthermore, we describe possible pathomechanisms and propose treatment options for delayed diagnosis of osteoarticular infection with Clostridium spp.
Case 1. A, A’: Closed dislocation fracture. B: Immediate lateral osteosynthesis after reposition. C and D: Within 3 months, inner demarcation of the cancellous bone of the tibial pilon.
Case 1
A 43-year-old non-smoking female farmer stumbled over a doorstep. Immediately afterwards she was admitted to the Emergency Department with a Gustilo grade 2 open, dislocated trimalleolar fracture of her lower left leg (Figure 1). Immediate reduction and internal fixation was performed. Due to fever and discharge of pus, revision was required on the sixth postoperative day. Bacteriology harvested at the sixth day showed clostridium species seven days later. The antibiotic therapy was completed according to resistance testing with metronidazole (Table I). Persistent pus production with open fistulae led to two further revisions, once presenting coagulase-negative Staphylococcus spp. Thereafter, the patient was referred to a tertiary centre 3 months after the accident, presenting with three persistent fistulae (Figure 1C). Debridement ended in removal of a large block of dead bone located in the centre of the epi-/metaphyseal area and additional small sequestrae, leaving a bone defect of about 6 cm length (Figures 1C, 2A and B). Histological analysis showed non-vital bone elements in the resected block and chronic inflammation of the surrounding granulation tissue, containing mainly plasma cells and lymphocytes as a sign of chronic infection (Figure 2C and D). External fixation was applied, which was completed 2 weeks later together with an oblique tibial osteotomy for callus distraction and segmental transportation according to Ilizarov (11). The aim of this procedure was to compensate leg shortening and to allow fusion of the ankle joint (Figure 3). Further bacteriological tests remained negative. At 45 weeks later, the external fixation was removed and an orthosis applied. Subsequently, the patient was able to ambulate fully, weight bearing with minor pain. Thirteen years after the ankle fusion, the patient experienced massive arthrosis of the subtalar ankle joint, requiring a subtalar fusion and a supramalleolar correction osteotomy due to an equinus position of the foot (Figure 3C). After 24 years, the patient has only minimal pain and takes no analgesics. She is able to walk independently and is satisfied with the final result, despite osteoarthrosis of the opposite hip.
Case 2
A 58-year-old woman fell into a 2-meter deep cesspool, sustaining a bimalleolar luxation fracture and type II soft tissue damage according to Gustilo (Figure 4A) (12). The patient was a non-smoker and diagnosed with type II diabetes. At 105 min after the accident, she was referred first to the regional hospital and then 5 h later to a secondary referral centre. There, she was given tetanus immunization and 1.5 mg cefuroxim thrice daily was administered parenterally for 5 days. Seven hours after the accident, a thorough debridement, reduction of the dislocation and stabilization with an external fixation was performed in the operating theatre. Open reduction and internal fixation were performed 4 days later (Figure 4B). Due to wound tension and swelling, negative pressure treatment (NPT) was applied laterally. After seven changes of the NPT, a smear from the lateral wound obtained 17 days after the accident showed Clostridium butyricum 7 days after cultivation. Twenty-five days later, removal of all the osteosynthesis and external fixation was necessary due to formation of an abscess (Table II). Magnetic resonance imaging (MRI) and computed tomographic scan showed inflammation of the distal tibia and osteopenia. To cover the soft-tissue defect, a free gracilis flap was performed using the secret scar technique (Figure 5) (13, 14). The external fixation was removed 11 weeks later and a nail-implantation inserted. Revision was then required to drain an abscess and to remove the nail. Scintigraphy and MRI after 5 months suggested the presence of sequestrating osteomyelitis of the tibial pilon, although the patient had no fever, redness or swelling around the ankle joint (Figure 4C). The patient was referred to a university hospital. The gracilis flap was elevated laterally and the bone exposed. A brownish-porous substance including cancellous sequestra was found and curetted out of the tibia (Figure 6A). The biopsies still contained the same bacteria (Table II). The histology showed necrotizing osteomyelitis and haematoid pigment with infiltration of bacteria. The ankle was fused with external fixation using the fibula as a bone bridge (Figure 6B). According to resistance testing, oral treatment with 500 mg metronidazole thrice daily was prescribed for a total of 12 weeks. The external fixation was removed 22 weeks later (Figure 6C). At the follow-up after 18 months, there were no signs of infection, with stable soft-tissue coverage. The patient was full weight-bearing without pain, and radiography showed bony union. Importantly, it was possible to replace the aircast walking boot with an adapted shoe.
Case 1. A: Medial revision presents a demarcation of the central tibial pilon. B: Resected parts of the pilon and the fibula. C: Undecalcified longitudinal section of the pilon, coloured with toluidine blue. An intact joint surface and a demarcated irregular cancellous bone surface are visible. D: Soft tissues of the area under high magnification show chronic infection with plasma cells and lymphocytes (10× magnification).
Chronology and therapy of case 1.
Case 1. A: Bone loss of the pilon of about 6 cm in length. B: Appearance at the end of callus distraction. C, C’: At 45 weeks later, the external fixation was removed and an orthosis applied. D: Thirteen years later subtalar arthrodesis combined with correction osteotomy of the distal tibia to overcome equinus position.
Case 2. A: Grade 2 open dislocation fracture helped with primary debridement and external fixation. B and C: Internal fixation 4 days later. D: Magnetic resonance imaging after 5 months with arrowheads showing strong evidence of sequestrae in the tibial pilon.
Chronology and therapy of case 2.
Case 2. Soft-tissue closure after 6 weeks. Appearance before (A and B) and after (C and D) the operation. The gracilis muscle was tunnelled medially to laterally.
Case 2. A, A’: Preoperative computed tomographic-scan through the tibial pilon area presenting a demarcation of the cancellous bone, which then was resected. B: Ankle fusion with external fixation. C and D: Fixation was removed 22 weeks later, when the fusion was solid enough.
Discussion
Our two cases are remarkable and show that Clostridium spp. can cause severe osteomyelitis after open epi- and metaphyseal tibial fractures. In both cases, local bone necrosis in the pilon tibial was the common finding. Whereas the epiphyseal bone necrosis was attributed to the open dislocation leading to a possible devascularisation (4), the extension into the metaphyseal area could not be explained by this mechanism as there are hardly vascular connections between the tibial meta- and epiphyses (15). In a recent study by Blanke et al., clinical manifestations and risk factors were identified for the development of post-traumatic osteonecrosis (PON) of the distal tibia. Therein, all identified risk factors were associated with heavy fracture mechanisms, leading most likely to serious devascularisation of at least parts of the distal tibial epiphysis (4). Seventy-five percent of patients with PON sustained fractures through a high-energy trauma mechanism, and the combination of tibiotalar dislocation, severe soft-tissue damage and type Weber C-fracture of lateral malleolus was associated with PON in all of the cases. Interestingly, late joint reduction, postoperative infection or bimalleolar fracture were not found at a higher proportion in patients with PON (4).
The patients were treated with a combination of radical and serial debridement of the bone, identification of the bacteria, antibiotic sensitivity testing, ankle arthrodesis and adequate long-term antibiotic treatment. Satisfactory long-term results, consisting of bony union, recovery of ambulatory ability and stability of scars were achieved. Therefore, a multidisciplinary team approach is recommended.
The genus Clostridium comprises more than 200 species and subspecies (http://www.dsmz.de). Different species of Clostridium are known to cause necrotizing tissue infection. Typical examples are C. perfringens causing gas gangrene and C. sordelli causing gynecological infections. The reasons for the potentially vast necrosis caused by infections with different types of Clostridium are several types of extracellular toxins with the potential to cause intravascular activation of platelets with consecutive formation of occlusive thrombi, destruction of cell membranes causing cell lysis, modulation of inflammatory response and modulation of signaling molecules that control the cell cycle, apoptosis and gene transcription (9). The intraoperative findings in our two cases with extensive bone necrosis indicate that the Clostridium species involved had the ability to form some type of toxin, causing tissue death.
Post-traumatic osteoarticular infections due to Clostridium species have rarely been reported in the literature. Open fracture management is guided by well-defined steps aimed at reducing the risk of suppurative infections (16). Furthermore, hyperbaric oxygen therapy may contribute to the management of anaerobic bone infections when used in combination with surgery and antibiotics (2).
In addition to the application of Advanced Trauma Life Support, tetanus management principles are critical (16). Nevertheless, the issues of appropriate antibiotic prophylaxis, ideal timing for operative debridement, and appropriate timing of wound closure after debridement are in constant evolution (16). Prompt administration of antibiotics, based on the grade of injury, can be viewed more as treatment for presumptive infection or contamination, rather than simply prophylaxis (17). Furthermore, it has been suggested that delay in admission to the definitive treating trauma center of more than 2 hours after injury was associated with a 5.4-fold increased risk of developing an infection (18).
Our report confirms that the identification of Clostridium species in specimens from an osteoarticular infection requires extremely extensive and aggressive surgical resection (2). Often, the implantation of fixation hardware on an emergency basis is followed initially by skin necrosis, delayed wound healing, and a seropurulent discharge (2). Other possible reasons for the persistence of infection are an inadequate initial antimicrobial drug regimen, poor diffusion of antibiotic treatment due to the presence of necrotic tissue and the formation of persisting endospores (19). It has been postulated that if a fracture is at risk of contamination with Clostridium, such as after farm-related injuries, penicillin should be added to the antibiotic regimen (20). Thus, the administration of cephalosporin in the case of patient 2 was potentially insufficient due to the severe contamination of the injury with liquid manure. Continuing the prophylactic antibiotics for longer than 48 h is not recommended, as this strategy may put selective pressure on the bacteria, thereby inducing endospore production (2). Despite a multitude of studies, there is no clear evidence of the superiority of a multiple-dose regimen compared with a single-dose one (21-24). However, patients having three or four peri-operative doses appear to have the lowest risk for re-operation at 10 years (21).
Ibnoulkhatib and co-workers retrospectively reviewed 12 patients with Clostridum spp. bone and/or joint infections complicating compound limb fractures with soil contamination and extensive soft-tissue damage. The median time to identification of Clostridium species was 14.5 days. Outcomes were assessed after a follow-up of at least 18 months following identification of the organism. In all 12 patients, the immediate outcome was unfavourable, requiring early reoperation (2).
Conclusion
Osteoarticular infections due to Clostridium spp. are rare but serious and require prompt and extensive treatment. Adequate antibiotic prophylaxis, early identification of disease-causing bacteria, antibiotic sensitivity testing, aggressive surgical treatment and possibly anatoxin-base anti-tetanus vaccine may prevent colonization and chronic infection.
Footnotes
Authors' Contributions
Study design: Mathias Tremp, Carlo M. Oranges, Dirk J. Schaefer, Daniel F. Kalbermatten, Peter E. Ochsner; Data acquisition and collection: Mathias Tremp, Carlo M. Oranges, Daniel F. Kalbermatten, Peter E. Ochsner; Manuscript drafting: Mathias Tremp, Carlo M. Oranges; Critical revision: all Authors. Final approval: all Authors.
This article is freely accessible online.
Conflicts of Interest
The Authors declare that they have no conflicts of interest. None of the Authors has a financial interest in any of the products, devices, or drugs mentioned in this article.
- Received October 6, 2019.
- Revision received October 20, 2019.
- Accepted October 22, 2019.
- Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
References
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.