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ORIGINAL ARTICLE
Year : 2023 | Volume
: 22
| Issue : 4 | Page : 434-439
Outcome of intramedullary nail coated with antibiotic-impregnated cement in chronic osteomyelitis
Pulak Sharma, Anurag Baghel
Department of Orthopaedics, Apex Trauma Center, SGPGI, Lucknow, Uttar Pradesh, India
Correspondence Address:
Pulak Sharma
Department of Orthopaedics, Apex Trauma Center, SGPGI, Lucknow, Uttar Pradesh
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/aam.aam_185_22
Abstract
Introduction: Chronic osteomyelitis (Chr OM) may result as a sequel of acute hematogenous infection or following open fractures or orthopedic surgeries. Among various osteoarticular infections, Chr OM is one of the most challenging in terms of treatment. In the present study, we evaluate the outcome of antibiotic cement-coated nails in the treatment of chronic pyogenic osteomyelitis and also discuss the future innovations in field of antibiotic-compatible biomaterials for coating the implants. Materials and Methods: Twelve cases of Chr OM (5 hematogenous and 7 exogenous following trauma or surgery) were operated by intramedullary nail coated with antibiotic-impregnated bone cement from September 2018 to January 2021. All the cases had bacteriological confirmation of infection by deep curettage and its subsequent culture sensitivity. K nail was used in 10 cases and elastic stable intramedullary nails were used in 2 cases. Results: Out of 12 cases, 8 were male and 4 were female. The average duration of follow-up was 13 months. Infection was controlled in all the cases (two cases required repeat antibiotic-coated nailing), and there was no incidence of relapse in any case. The control of infection was assessed by clinical assessment and laboratory parameters. Conclusion: Antibiotic cement-coated nails are an effective method in local control of infection in Chr OM without any systemic side effect.
Résumé
Introduction: L'ostéomyélite chronique (OM Chr) peut résulter d'une infection hématogène aiguë ou de fractures ouvertes ou chirurgies orthopédiques. Parmi les diverses infections ostéoarticulaires, Chr OM est l'une des plus difficiles en termes de traitement. Dans le présent étude, nous évaluons les résultats des ongles recouverts de ciment antibiotique dans le traitement de l'ostéomyélite pyogénique chronique et discutons également de l'avenir innovations dans le domaine des biomatériaux compatibles avec les antibiotiques pour le revêtement des implants. Matériels et méthodes: Douze cas de Chr OM (5 hématogènes et 7 exogènes à la suite d'un traumatisme ou d'une chirurgie) ont été opérés par clou centromédullaire enduit d'os imprégné d'antibiotique ciment de septembre 2018 à janvier 2021. Tous les cas ont eu une confirmation bactériologique de l'infection par curetage profond et sa sensibilité culturelle. Un clou K a été utilisé dans 10 cas et des clous centromédullaires stables élastiques ont été utilisés dans 2 cas. Résultats: Sur 12 cas, 8 étaient hommes et 4 femmes. La durée moyenne de suivi était de 13 mois. L'infection a été contrôlée dans tous les cas (deux cas ont nécessité une répétition enclouage enduit d'antibiotique), et il n'y a eu aucune incidence de rechute dans tous les cas. Le contrôle de l'infection a été évalué par une évaluation clinique et paramètres de laboratoire. Conclusion: Les ongles enduits de ciment antibiotique sont une méthode efficace dans le contrôle local de l'infection chez les Chr OM sans tout effet secondaire systémique.
Mots-clés: Ciment antibiotique, ostéomyélite chronique, clous centromédullaires
Keywords: Antibiotic cement, chronic osteomyelitis, intramedullary nails
Introduction 
Chronic osteomyelitis (Chr OM) is a progressive inflammatory process caused by pathogens, resulting in bone destruction and sequestrum formation.[1] The most common pathogens responsible for osteomyelitis in humans are Staphylococcus species, followed by Enterobacteriaceae and Pseudomonas species. Osteomyelitis associated with an implant is caused by Staphylococcus epidermidis more than 90% of the time.[2]
Chr OM is one of the most challenging clinical conditions in terms of treatment. Many of these patients have associated joint stiffness, soft tissue contractures, inadequate nutrition, and poor skin condition along with a history of multiple failed surgeries and a prolonged hospital stay. Antibiotic resistance, poor financial condition, and multiple consultations from different doctors make the situation even more challenging.
Historically, long duration of antibiotic treatment in combination with extensive surgical debridement was used in the management of Chr OM.[3] Systemic antibiotic therapy is not able to provide a minimum inhibitory concentration at the site of pathology, and this is further worsened by an impaired blood supply and formation of biofilm.[4] As a result, there was a shift in focus toward local antibiotic delivery in adjunct with surgical debridement.[5] Local delivery of antibiotics requires a suitable carrier. Polymethylmethacrylate (PMMA) bone cement is the most commonly used and widely available carrier for this purpose. Initially, antibiotics mixed with bone cement were used as blocks, gradually there was a shift toward the use of antibiotic beads, to deliver high doses of antibiotics at the site of pathology.[5],[6] One drawback with PMMA beads was that it did not provide any structural support to the diseased bone and required removal, which at times was difficult due to fibrosis. The issue of decreased vascularity and biofilm at the infection site remained unaddressed with the use of beads.[6]
The rationale for intramedullary antibiotic cement is an extension of the known utility of antibiotic-impregnated bone cement in the treatment of osteomyelitis.
There are four key principles in the treatment of osteomyelitis given by Cierny:[7]
Debridement and dead space managementStabilizationSoft tissue coverageAdequate antibiotic administration.The use of an antibiotic-coated nail in the treatment of long-bone osteomyelitis directly addresses three of these four principles. An antibiotic nail provides local antibiotic administration to the intramedullary canal, fills up the canal's dead space, and also provides stability to the bone. Reaming of the bone and debridement at the time of surgery increases the vascularity of the diseased area and takes care of the biofilm.
The aim of this study is to describe the outcome of antibiotic nail in chronic pyogenic osteomyelitis, in terms of remission of infection and relapse after remission.
Materials and Methods A prospective experimental study was conducted in the specialty of orthopedics, in a Level 1 trauma center after obtaining clearance from the institutional ethical committee. Fourteen consecutive adult patients with diaphyseal or metaphyseo-diaphyseal pyogenic Chr OM were operated from September 2018 to January 2021. Two patients were lost to follow-up and were excluded from the study.
Inclusion criteria
Age >18 yearsCulture-proven diaphyseal or metaphyseo-diaphyseal pyogenic osteomyelitis of more than 6-week duration with radiologic evidence of sequestrum formation or sclerosisLong-bone involvement.Exclusion criteria
Age <18 yearsPathological fracturesNonpyogenic osteomyelitis (e.g., fungal or tubercular)Any previous surgery with antibiotic-impregnated PMMA bead/coated nailInfected nonunionSmall bone involvement.Procedure
All patients were assessed clinically (for site/pain/swelling/discharging sinus), hematologically (for baseline erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] values), microbiologically (culture and sensitivity), and radiologically (nature/extent of lesion). Preoperative cultures were taken from the depth of sinus tract. In cases where there was no sinus present, bone and marrow biopsies were taken and sent for histopathology and culture and sensitivity. Radiological evaluation included plain radiography, computed tomography, and magnetic resonance imaging to evaluate the pathology with reference to bone and soft tissues.
After optimizing the host condition, the patients were taken up for surgery. All patients were operated under spinal anesthesia. Debridement and excision of the sinus or drainage of associated pyomyositis was performed first. Thereafter, the patients were taken up for the intramedullary procedure.
Entry for the nail was made under C arm guidance. Subsequently, the canal was sequentially reamed with flexible reamers of progressively increasing sizes. The reamed material was sent for histopathology, culture, and sensitivity. Once the canal has been prepared an infant feeding tube was placed and inside the canal and it was lavaged with one liter of normal saline containing 100 ml of hydrogen peroxide and 100 ml of 5% povidone-iodine solution. A suction tip was placed at the entry site of the nail, to create a negative pressure so that the whole of the canal gets thoroughly irrigated with the solution. This exercise was repeated with one lit of unadulterated normal saline to wash away all the povidone-iodine and hydrogen peroxide from the canal.
While the canal was being prepared, the second surgical team prepared the antibiotic nail. K nail or elastic stable intramedullary nails were used for this purpose. High-viscosity PMMA bone containing 1 g gentamicin (aminoglycoside) was mixed with 4 g of vancomycin (glycopeptides) in all the cases. Coupling of a glycopeptide with an aminoglycoside covered both Gram-negative and Gram-positive bacteria. Nails coated with antibiotic-impregnated bone cement were inserted from the entry site and its distal and proximal levels were checked under an image intensifier.
The patient was allowed partial weight bearing from the 2nd postoperative day. Intravenous antibiotics were given for 7 days followed by 4 weeks of oral antibiotics. The choice of antibiotics was based on preoperative culture and sensitivity results. Follow-up was done every 6 weeks for the first two visits and later every 3 months till 1 year.
In each visit, the patient was assessed for remission and recurrence of infection. The assessment was done clinically (pain, swelling, and persistence of sinus), hematologically (total leukocyte count, ESR, and CRP), and radiologically (improvement of bone quality).
Remission was declared when the patient had improvement in all the parameters clinical (decrease in pain and swelling and healing of sinus), hematological (normalization of ESR and CRP values), and radiological (improvement in bone quality). In cases where the infection did not undergo remission even at 6 weeks postsurgery, the procedure of antibiotic cement-coated nailing was repeated. All the patients with antibiotic nails were counseled for exchange nailing with standard interlocking nail after 6 weeks of surgery if the remission has been achieved. Treatment was considered a failure if there was no clinical remission even after 6 weeks of the second surgery.
Observations and Results Twelve cases were (8 males and 4 females) included in the study. The mean age of patients was 30 years (20–58 years). Five were hematogenous in origin, four patients had a history of compound fracture, and 3 cases were postoperative diaphyseal Chr OM with implant in situ. Eight cases had involvement of the femur and 4 cases had involvement of tibia. Staphylococcus aureus was isolated in most of the cases (9/12). Coagulase-negative Staphylococcus (3/12) and Escherichia coli (1/12) were other organisms which were isolated.
Organisms isolated were commonly resistant to penicillin, ampicillin, tetracycline, and erythromycin and were sensitive to vancomycin, levofloxacin, and gentamycin.
Discharging sinus healed by 2 weeks in 7 cases; in 3 cases, healed at 4 weeks, and in 2 cases, there was persistence of sinus at 6 weeks, for which a repeat surgery was performed. The sinuses in these patients eventually healed at 2 weeks following the second surgery. The mean follow-up of patients was 13 months (12–16).
Hematological parameters normalized at 3 weeks in most of the cases (10/12), and in two cases (which required a second surgery), the parameters normalized at 8 weeks from the first surgery. All the cases achieved remission, and there was no relapse in any of the cases at the end of 1 year of follow-up after surgery [Figure 1] and [Figure 2].
Figure 1: Chronic OM of femur with diaphyseal involvement (a and b), treated by antibiotic nail prepared over K nail (c). Exchange nailing with standard interlocking nail was done at 6 weeks. Clinical and radiological picture at 1-year follow-up (d and e) OM = Osteomyelitis
Figure 2: Diffuse diaphyseal involvement of femur with associated pyomyositis (a and b), treated by antibiotic nail prepared over K nail (c). Exchange nailing with standard interlocking nail was done at 6 weeks. Clinical and radiological picture at 13-month follow-up (d and e)K nail was used in 10 cases and elastic stable titanium nails were used in 2 cases. All the patients were taken up for exchange nailing between 6 and 10 weeks after surgery, which had led to remission of their disease (first surgery in 10 cases and second surgery in 2 cases). We encountered dissociation of cement and nail complex in one case at the time of exchange nailing. The cement could not be completely removed from the canal, and the procedure was abandoned. The patient remained asymptomatic at the end of the study [Figure 3].
Figure 3: Diffuse diaphyseal involvement of femur with associated soft tissue component (a and b). The medullary canal was narrow and dysmorphic, so the antibiotic nail prepared over TENS (c). Exchange nailing was attempted at 6 weeks following remission, but there was dissociation between cement and nail. Clinical and radiological picture at 13-month follow-up, the patient is asymptomatic with no relapse (d and e). TENS = Titanium elastic nail system Discussion Around 30 years back, Belches and Engelbrecht had reported that penicillin, erythromycin, and gentamicin introduced into the bone cement for surgeries around hip resulted in spread of these antibiotics into the surrounding tissues for months, leading to a prolonged local concentration of antibiotic in the tissues.[8] These findings led to an interest in the application of cement impregnated with antibiotic in the treatment of osteomyelitis. Klemm introduced gentamicin in cement beads, as an alternative to the introduction of large deposits of antibiotic cement at the site of infection, and used them as a temporary filler for the gap that was created after the removal of necrotic tissue.[9] Since then, several studies have been undertaken to study the role of local antibiotic delivery in orthopedic infections.[5],[6],[10],[11],[12]
More recently, there has been a shift toward the use of antibiotic-coated intramedullary devices or cement rods containing antibiotics in the medullary cavity, which deliver drugs directly at the site of pathology.[13],[14],[15],[16],[17],[18],[19],[20],[21] This concept of combining the need for fixation and infection control in osteomyelitis was first published by Klemm et al.[20] in 1988, but it was a very primitive stage at that time. The idea of directly combining intramedullary stabilization with local anti-infective therapy gained acceptance when Darouiche et al.[21] used it in an animal study. Since then, there have been numerous studies which applied this principle to humans [Table 1].
Table 1: Summary of similar studies of antibiotic-impregnated cement-coated nails in treatment of osteomyelitisBarger et al.[22] and Koury et al.[23] reviewed the concept of antibiotic nail in the treatment of long-bone infections. Both the reviews on this technique shared a similar conclusion that antibiotic cement nails offered a useful and relatively simple technique to treat intramedullary osteomyelitis of the long bones. The results of the present study reaffirm the findings given by the above authors. Out of 12 cases included in the study, all had a clinical remission, and there was no relapse at the end of 1 year postsurgery.
There have been reports in the literature that have expressed concerns regarding the use of intramedullary antibiotic delivery systems. The main objections are the unpredictable and inconsistent antibiotic release, possibility of development of antibiotic resistance, and fears regarding toxicity from the absorption of methyl methacrylate (MMA) monomers via the carboxylesterase-mediated conversion of MMA to methacrylic acid. These reports have been only sporadic, and no consistent finding has yet been established. The use of antibiotic-impregnated cement has shown a consistent and reproducible result in a variety of anatomic locations, including the tibia, femur, humerus, knee, and ankle.[24],[25] The concerns regarding its safety have not been validated till date, and there is ample of evidence from animal models and published reports to support their use.[22],[23]
The antibiotic nail shows a promising result, but the system is not yet perfect. The technique has its own limitations. Only a limited spectrum of medicines can be used in its preparation, due to the essential clause of heat stability for antibiotics to be used. Bone cement occupies space which necessitates the use of smaller diameter nail, thereby decreasing the sturdiness of the construct. Furthermore, the long-term presence of cement presents the theoretical possibility of bacterial adhesion and biofilm formation. Several innovations are being done to overcome the limitations and come up with an ideal antibiotic nail.
Berebichez-Fridman et al.[26] proposed the development of an intramedullary nail coated with bacteria-specific antibiotics and growth factor nanoparticles for the treatment of OM, infected nonunions, infected malunions, and arthrodesis of the joints. It is believed that this will not only ensure antimicrobial effects but will also stimulate osteoblastic differentiation and proliferation, thus enhancing the formation of healthy bone tissue and providing stable and strong fixation of the bone. With advances in technologies, it may be possible to see such an implant in near future.
Metsemakers et al.[27] used doxycycline-loaded polymer-lipid encapsulation matrix (PLEX) in animal models of methicillin-susceptible S. aureus and methicillin-resistant S. aureus-contaminated intramedullary nailing. PLEX is a biodegradable material that can be spray-coated onto orthopedic implants, and it also permits the use of nonheat stable antibiotics. A more sustained release of antibiotic was detected and the bactericidal levels were maintained for a period of 4 weeks. At the end of 4 weeks, there was radiographic evidence of osteomyelitis in all control animals, and none in doxycycline-PLEX-treated animals.
Tsuchiya et al.[28] carried out a trial in which 64 patients with active surgical site infections and 158 patients with compromised clinical status (diabetes mellitus, cancer, the use of chemotherapy, or systemic corticosteroids) and/or contaminated bone defects were treated with various iodine-supported titanium implants. Iodine-containing anodic oxides are a very promising development in the treatment of infection during the use of orthopedic instrumentation. Iodine-coated implants have a wider spectrum of antimicrobial activity, do not require removal, and have no effect on bone healing or thyroid physiology. The results of the clinical trial were very promising, all the patients with active infection recovered, and in clinically compromised patients, only 3 had infection which settled with the use of systemic antibiotics.
Kose et al.[29] used silver ion-doped ceramic nanopowder coating in animal models. The results were promising with no evidence of systemic effects of silver ion on the animals. The use of silver rather than antibiotics is hypothesized to be advantageous because it demonstrates a wide spectrum of bacterial killing and resistance has not been described.
Giavaresi et al.[30] used Defensive Antibacterial Coating (DAC) which is a bioabsorbable adhesive hydrogel, in animal models with promising results. There was no bacteremia which occurred in controls, and DAC had no effect on the underlying histology of the bone. It is also hypothesized to prevent biofilm formation. The disadvantage is its short duration of action which is only 24 h.
Conclusion There is no single modality of treatment for Chr OM which is universally acceptable. The surgical options available for patients included debridement, sequestrectomy, curettage, and antibiotic beads placement. Intramedullary nails coated with antibiotic-impregnated bone cement can be a useful addition to the existing armamentarium against Chr OM. They have been shown to provide high rates of infection control in addition to osseous stability. Preliminary results of this procedure are very promising, further long-term multicentric randomized controlled trials are needed to validate the usefulness.
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Conflicts of interest
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References 
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