Technical Note
479
Antibiotic-Impregnated Cement Embedding Technique for Spinal Instrumentation Infections Takahiro Hozumi1
Kiyofumi Yamakawa1
1 Department of Orthopaedic Surgery and Musculoskeletal Oncology,
Tokyo Metropolitan Komagome Hospital, Tokyo, Japan J Neurol Surg A 2014;75:479–484.
Abstract
Keywords
► spinal instrument ► infection ► antibiotic impregnated cement ► embedding
Taiji Kondo1
Address for correspondence So Kato, MD, Department of Orthopaedic Surgery, Sensory and Motor System Medicine, The University of Tokyo, Graduate School of Medicine, Surgical Sciences, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan (e-mail: [email protected]).
Background and Study Aims When surgical site infection occurs in patients with an instrumented spine, the management of infection is challenging because a biofilm is formed around the metallic surface of the implant. Although a wide variety of methods to salvage implants has been developed, previously reported methods reduce the patients’ quality of life and are frequently time consuming and costly. Patients and Methods We performed a cement embedding technique in 13 consecutive patients with infection after spinal instrumentation. After meticulous open débridement, the metallic implants were embedded using polymethylmethacrylate (PMMA) mixed with antibiotics. Antibiotics were selected in each case according to the pathogens and their sensitivity. The wound was primarily closed. We did not restrict the patients’ activity postoperatively. The implants were not removed unless it was necessary for further procedures. Results Nine patients, including those infected by methicillin-resistant Staphylococcus aureus (MRSA), were cured by débridement and PMMA embedding followed by systemic antibiotic treatment. No complications were reported. Conclusions The antibiotic-impregnated PMMA embedding technique is an effective method for the treatment of spinal instrumentation infections. It is easy to perform and is also effective for MRSA infection.
Introduction Spinal instrumentation is thought to be a risk factor for deep surgical site infection (SSI).1 When SSI occurs in patients with an instrumented spine, the management of the infection is more challenging compared with that for SSI without instrumentation. Although some authors have reported that a biofilm shows lower adhesion ability to titanium in comparison with stainless steel2 and modern titanium alloy implants are thought to have a reduced need for removal in case of infection, we are still confronted with devastating cases that cannot be treated conservatively. To avoid implant removal that could cause spinal instability, a wide variety of methods has been developed to achieve preservation of infected spinal
received October 23, 2013 accepted after revision November 15, 2013 published online June 27, 2014
Takahiro Goto1
implants. Historically early repetitive débridement was advocated as the optimal strategy for implant preservation.3,4 Currently, closed-suction irrigation system5–8 and vacuumassisted closure (VAC)9–14 are the two most commonly reported techniques. However, these methods still lead to longstanding restriction of activities of daily living (ADLs) for patients, necessitate human resources and is expensive. Therefore, simpler and more cost-effective methods of implant salvage are needed. Antibiotic-impregnated polymethylmethacrylate (PMMA) has been widely used in infections following joint replacement surgery.15,16 With regard to spine surgery, the use of PMMA beads for infected instrumentation was reported in 1990s.17 We developed a novel simple PMMA embedding
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1371519. ISSN 2193-6315.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
So Kato1
Journal of Neurological Surgery—Part A
Vol. 75
F
M
62
68
62
63
72
68
57
35
49
63
50
3
4
No. A6/2014
5
6
7
8
9
10
11
12
13
L2 OCF, kyphosis
C6 metastasis
C4–C6 metastasis
C5–C6 pseudoarthrosis
T11–L1 osteosarcoma
None
Malignancy
Malignancy
None
DM, malignancy, CRF
DM, malignancy, CRF
RA
Malignancy
Steroid use
Steroid use
Malignancy
DM, malignancy
RA
Comorbidity
Multiple previous operations
Previous radiation therapy
Previous radiation therapy
Smoking
Multiple previous operations, previous radiation therapy
Multiple previous operations
Multiple previous operations
Multiple previous operations, previous radiation therapy
Other risk factors for SSI
L2 PSO, T11–L5 PSF
C4–C7 LN, C4–C7 PSF
C3–C7 LN, C2–T1 PSF
C5–C6 PSF
T10–12 LN, T9–L2 PSF
T12–L1 LN, T11–L3 PSF
L1–L2 PSO, T10–L4 PLF
T2–T4 LN, T1–T5 PSF
L1–L5 PLIF
L4–S1 PLF
T4–T7 LN, T2–L1 PSF
C1 LN, Occiput–C4 PSF
Occipt–C5 PSF
Initial operation
535
273
433
158
243
209
401
211
406
223
220
180
325
Length of initial operation, min
3270
1730
1340
290
380
130
790
230
700
290
1230
1020
235
Blood loss, mL during initial operation
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Abbreviations: CRF, chronic renal failure; DM, diabetes mellitus; LN, laminectomy; OCF, osteoporotic compression fracture; PLF, posterolateral fusion; PLIF, posterior lumbar interbody fusion; PSF, posterior spinal fusion; PSO, pedicle subtraction osteotomy; RA, rheumatoid arthritis; SAS, subaxial subluxation; SSI, surgical site infection.
F
M
M
L1 metastasis
L1–L2 OCF, kyphosis
T3 metastasis
L4 OCF
L5 OCF
T4–T12 metastasis
C1–C2 metastasis
C4–C5 SAS
Disease
Antibiotic-Impregnated Cement Embedding Technique
M
F
F
F
F
F
M
63
2
F
Sex
72
Age, y
1
Case
Table 1 Patient demographic data
480 Kato et al.
Antibiotic-Impregnated Cement Embedding Technique
Patients and Methods Among the patients who underwent instrumentation in our service between January 1995 and May 2011, 25 patients were diagnosed with deep SSI. We used the antibiotic-impregnated PMMA embedding technique for 13 consecutive patients (five men and eight women) beginning February 2004. ►Table 1 summarizes the demographic data of the patients. The diagnosis of SSI was confirmed by physical findings, laboratory data, and/or radiographic findings. The median time interval between the primary operation and the diagnosis of SSI was 8 days (range: 5–33 days). The pathogens and their sensitivity to antibiotics were identified by blood culture and stab culture of the infected wound. The pathogen was methicillin-resistant Staphylococcus epidermidis (MRSE) in six, methicillin-sensitive Staphylococcus aureus in three, methicillin-resistant Staphylococcus aureus (MRSA) in two and Enterobacter cloacae in two patients.
Surgical Technique Once the diagnosis of SSI was confirmed, the patient was transferred to the operating room for open débridement of all infected tissues. Large-volume irrigation using normal saline was performed. Implant loosening was ruled out. The PMMA powder was manually mixed with the antibiotic powder (typically 3.0 g of vancomycin per 20 g of PMMA); both were then meticulously mixed with the liquid monomer in the closed mixing bowl until the mixture became completely homogeneous. After the antibiotic-impregnated PMMA became moldable, the whole metallic surface was embedded (►Fig. 1). If the pathogen was not yet identified, vancomycin was empirically given. Otherwise, the antibiotic was selected according to the pathogen and its sensitivity: These antibiotics were included gentamicin, meropenem, and ceftriaxone. A closed suction drain was placed subfascially, and the wound was primarily closed. Intravenous antibiotics were administered for 6 weeks in most cases, followed by oral
481
antibiotics as needed. The drainage was removed within 7 days postoperatively. We did not restrict the patients’ activity after surgery. All patients were discharged after wound healing and normalization of C-reactive protein and erythrocyte sedimentation rate. The treatment was considered successful if laboratory data and clinical findings ruled out recurrence after the discontinuation of oral antibiotics.
Results ►Table 2 shows the details of SSI and subsequent treatment. One patient with spinal metastasis died of tumor progression unrelated to infection 9 weeks after the operation (case 9). In the other patients, the median follow-up period was 1.5 years (range: 3.8 months to 8.2 years). Nine patients were cured; postoperative spinal stability was confirmed radiographically. No complications attributable to the embedding technique were observed throughout the treatment course. In three patients, we failed to control the infection. One of them was cured by implant removal (case 5). In the other two with a history of radiation therapy for spinal metastasis (cases 3 and 8), we did not removed their implants due to concerns about stability because of massive vertebral invasion and switched to VAC treatment. However, the infections could not be controlled until their deaths. In summary, 10 of 13 patients were cured in terms of infection control, and 9 of these 10 cured patients (90%) were successfully treated with implant salvage. In comparison, before we established this antibiotic PMMA embedding technique, 10 of 12 patients were cured, but only 3 (30%) underwent standardized repetitive open débridement without implant removal.
Case Presentation (Case 13) A 50-year-old woman with lumbar kyphosis due to L2 osteoporotic compression fracture underwent L2 pedicle subtraction osteotomy in combination with T11–L5 posterior spinal fusion. Surgical procedure was successfully completed, but wound secretion did not cease and dehiscence subsequently occurred. She had a fever of 39°C on the eighth postoperative day, and stab culture showed gram-positive
Fig. 1 Scheme of antibiotic-impregnated polymethylmethacrylate (PMMA) embedding technique. (A) First operation: Posterior decompression and fusion. (B) Second operation for infection: PMMA embedding. Journal of Neurological Surgery—Part A
Vol. 75
No. A6/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
technique for infected implants and have used this method since 2004. In the present case series, we report the outcomes and discuss its effectiveness.
Kato et al.
Journal of Neurological Surgery—Part A
63
62
68
62
63
72
68
57
35
49
63
50
2
3
Vol. 75
4
5
6
No. A6/2014
7
8
9
10
11
12
13
F
M
M
F
M
M
F
F
F
F
F
M
F
Sex
8
7
33
6
16
14
8
16
9
5
7
5
9
Time to infection, d
Wound secretion, wound dehiscence
Wound secretion, redness
Wound secretion, redness
Wound secretion, fever, pain
Wound secretion, wound dehiscence
Wound secretion, fever
Wound secretion, fever
Wound secretion, fever, redness
Wound secretion, fever
Pain
Wound secretion, redness
Fever, pain
Wound secretion, fever
Initial symptoms of infection
MRSA
MSSA
MRSE
MRSE
MRSA
E. cloacae
MSSA
E. cloacae
MSSA
MRSE
MRSE
MRSE
MRSE
Causative organism
8
34 29 10 14 10 17 11
VCM 4.0 g þ PMMA 30 g MEPM 2.0 g, CTRX 2.0 g þ PMMA 40 g VCM 4.0 g þ PMMA 20 g VCM 3.0 g þ PMMA 20 g VCM 2.0 g þ PMMA 20 g VCM 3.0 g þ PMMA 20 g VCM 4.0 g, MEPM 4.0 g þ PMMA 40 g
23
VCM 1.5 g þ PMMA 10 g 11
12
GM 420 mg þ PMMA 20 g
12
VCM 2.0 g þ PMMA 10 g VCM 3.0 g þ PMMA 20 g
MEPM 2.0 g þ PMMA 20 g
46
Total duration of systemic antibiotics, wk
VCM 3.5 g þ PMMA 20 g
Antibiotic used with PMMA embedding
Cured
Cured
Cured
Cured
N/A
Failed
Cured
Cured
Failed
Cured
Failed
Cured
Cured
Result of operation for SSI
None (death)
VAC
Implant removal
VAC
Salvage procedure
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Antibiotic-Impregnated Cement Embedding Technique
Abbreviations: CTRX, ceftriaxone; E. cloacae, Enterobacter cloacae; GM, gentamicin; MEPM, meropenem; MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; MSSA, methicillin-sensitive Staphylococcus aureus; PMMA, polymethylmethacrylate; VAC, vacuum-assisted closure; VCM, vancomycin. a Thirteen consecutive patients with instrumentation infection underwent the polymethylmethacrylate embedding technique.
72
Age, y
1
Case
Table 2 Details of surgical site infection and subsequent treatmenta
482 Kato et al.
Antibiotic-Impregnated Cement Embedding Technique
Kato et al.
483
cocci. We made the diagnosis of SSI. After meticulous open débridement, the antibiotic-impregnated PMMA embedding technique was performed. Vancomycin and meropenem were selected empirically to cover MRSA as well as gram-negative germs, and they were mixed with 40 g of PMMA. The intraoperative picture is shown in ►Fig. 2. Because the causative organism turned out to be MRSA postoperatively, intravenous administration of vancomycin was continued for 5 weeks, followed by oral administration of clindamycin and rifampicin for 6 weeks. The wound healing was uneventful, and all laboratory data normalized rapidly. The patient was followed 18 months without signs of recurrence.
Discussion We reported the treatment outcomes of patients with deep SSI after spinal instrumentation undergoing the antibioticimpregnated PMMA embedding technique. This technique can be easily performed with no complications. It was also effective for MRSA infection. We suggest that spine surgeons consider this technique a useful option. Two factors make the treatment of instrumentation infections challenging. First, the bacteria can adhere to the metallic surfaces of the instrumentation in case of SSI.18,19 The cluster of bacteria forms a self-produced polymer matrix (glycocalyx, also known as a biofilm) that protects them and confers a much higher tolerance to antibiotics.6 The minimal inhibitory concentration and minimal bactericidal concentration of antibiotics are considered to be 100- to 1000-fold higher. Second, implant removal to eradicate infection seems reasonable,20,21 but results in spinal instability restricting the patients ADLs or even requiring bed rest until the infection is successfully controlled and re-instrumentation can be performed. As an option for implant salvage, antibiotic-impregnated PMMA has been used to treat SSI, and many authors reported good results with infection control after joint replacement surgeries.15,16 The local concentration of antibiotics is maintained over a few weeks by release from the impregnated PMMA with minimal systemic toxicity.22 For infections after spinal instrumentation, Glassman et al first reported successful instrumentation salvage in 1996.17 They packed a chain of
antibiotic-impregnated PMMA beads into the gutter lateral to the instrumentation. This technique is easy to perform, but has the drawbacks that the cement beads create a large dead space due to their bulky profile and are prone to dislodgement into the spinal canal. In the present study, we avoid these drawbacks by embedding the implants in the antibioticimpregnated PMMA, making the whole complex low profile and minimizing the risk of dislodgement. Our technique does not require prolonged bed rest and re-surgery for PMMA removal. Among our successfully treated patients were some with MRSA infection, which is considered to be difficult to control without implant removal. Possibly, this is related to a much higher local concentration of the antibiotic than in other management protocols, because the antibiotic-impregnated PMMA directly cover the biofilm. Further studies are needed to investigate local pharmacodynamics of antibiotics released from impregnated PMMA to clarify the mechanism of its effectiveness.
Conclusion Antibiotic-impregnated PMMA embedding technique is an effective method for treating infections after spinal instrumentation without implant removal. It is easy to perform and could also be effective for MRSA infection. We suggest that spine surgeons consider this technique as the first-line treatment.
References 1 Smith J, Bhatia NN. Postoperative spinal infections. In: Herkowitz
HN, Garfin SR, Eismont FJ, Bell GR, Balderston RA, eds. RothmanSimeone The Spine. Philadelphia, PA: Elsevier Saunders; 2011: 1789–1803 2 Sheehan E, McKenna J, Mulhall KJ, Marks P, McCormack D. Adhesion of Staphylococcus to orthopaedic metals, an in vivo study. J Orthop Res 2004;22(1):39–43 3 Aydinli U, Karaeminoğullari O, Tişkaya K. Postoperative deep wound infection in instrumented spinal surgery. Acta Orthop Belg 1999;65(2):182–187 4 Weinstein MA, McCabe JP, Cammisa FP Jr. Postoperative spinal wound infection: a review of 2,391 consecutive index procedures. J Spinal Disord 2000;13(5):422–426 Journal of Neurological Surgery—Part A
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This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Fig. 2 Demonstrative case (case 13) in which the antibiotic-impregnated polymethylmethacrylate (PMMA) embedding technique was used. Right: cranial, left: caudal. (A) After débridement. (B) The whole implant was embedded in PMMA.
Antibiotic-Impregnated Cement Embedding Technique
Kato et al.
5 Levi AD, Dickman CA, Sonntag VK. Management of postoperative
6
7
8
9
10
11
12
13
infections after spinal instrumentation. J Neurosurg 1997;86(6): 975–980 Vender JR, Hester S, Houle PJ, Choudhri HF, Rekito A, McDonnell DE. The use of closed-suction irrigation systems to manage spinal infections. J Neurosurg Spine 2005;3(4):276–282 Chikawa T, Sakai T, Bhatia NN, et al. Retrospective study of deep surgical site infections following spinal surgery and the effectiveness of continuous irrigation. Br J Neurosurg 2011;25(5): 621–624 Ido K, Shimizu K, Nakayama Y, Shikata J, Matsushita M, Nakamura T. Suction/irrigation for deep wound infection after spinal instrumentation: a case study. Eur Spine J 1996;5(5):345–349 Mehbod AA, Ogilvie JW, Pinto MR, et al. Postoperative deep wound infections in adults after spinal fusion: management with vacuum-assisted wound closure. J Spinal Disord Tech 2005;18(1): 14–17 Ploumis A, Mehbod AA, Dressel TD, Dykes DC, Transfeldt EE, Lonstein JE. Therapy of spinal wound infections using vacuumassisted wound closure: risk factors leading to resistance to treatment. J Spinal Disord Tech 2008;21(5):320–323 Jones GA, Butler J, Lieberman I, Schlenk R. Negative-pressure wound therapy in the treatment of complex postoperative spinal wound infections: complications and lessons learned using vacuum-assisted closure. J Neurosurg Spine 2007;6(5):407–411 Labler L, Keel M, Trentz O, Heinzelmann M. Wound conditioning by vacuum assisted closure (V.A.C.) in postoperative infections after dorsal spine surgery. Eur Spine J 2006;15(9):1388–1396 Vicario C, de Juan J, Esclarin A, Alcobendas M. Treatment of deep wound infections after spinal fusion with a vacuum-assisted
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15
16
17
18
19 20
21
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device in patients with spinal cord injury. Acta Orthop Belg 2007;73(1):102–106 Ahmed R, Greenlee JD, Traynelis VC. Preservation of spinal instrumentation after development of postoperative bacterial infections in patients undergoing spinal arthrodesis. J Spinal Disord Tech 2012;25(6):299–302 Pitto RP, Spika IA. Antibiotic-loaded bone cement spacers in twostage management of infected total knee arthroplasty. Int Orthop 2004;28(3):129–133 Hanssen AD, Spangehl MJ. Practical applications of antibioticloaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res 2004;(427):79–85 Glassman SD, Dimar JR, Puno RM, et al. Salvage of instrumental lumbar fusions complicated by surgical wound infection. Spine (Phila Pa 1976) 1996;21(18):2163–2169 Gristina AG, Costerton JW. Bacterial adherence to biomaterials and tissue. The significance of its role in clinical sepsis. J Bone Joint Surg Am 1985;67(2):264–273 Donlan RM. Biofilm formation: a clinically relevant microbiological process. Clin Infect Dis 2001;33(8):1387–1392 Richards BR, Emara KM. Delayed infections after posterior TSRH spinal instrumentation for idiopathic scoliosis: revisited. Spine (Phila Pa 1976) 2001;26(18):1990–1996 Hedequist D, Haugen A, Hresko T, et al. Failure of attempted implant retention in spinal deformity delayed surgical site infections. Spine (Phila Pa 1976) 2009;34(1):60–64 Seligson D, Mehta S, Voos K, Henry SL, Johnson JR. The use of antibiotic-impregnated polymethylmethacrylate beads to prevent the evolution of localized infection. J Orthop Trauma 1992;6(4): 401–406
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
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479
Antibiotic-Impregnated Cement Embedding Technique for Spinal Instrumentation Infections Takahiro Hozumi1
Kiyofumi Yamakawa1
1 Department of Orthopaedic Surgery and Musculoskeletal Oncology,
Tokyo Metropolitan Komagome Hospital, Tokyo, Japan J Neurol Surg A 2014;75:479–484.
Abstract
Keywords
► spinal instrument ► infection ► antibiotic impregnated cement ► embedding
Taiji Kondo1
Address for correspondence So Kato, MD, Department of Orthopaedic Surgery, Sensory and Motor System Medicine, The University of Tokyo, Graduate School of Medicine, Surgical Sciences, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan (e-mail: [email protected]).
Background and Study Aims When surgical site infection occurs in patients with an instrumented spine, the management of infection is challenging because a biofilm is formed around the metallic surface of the implant. Although a wide variety of methods to salvage implants has been developed, previously reported methods reduce the patients’ quality of life and are frequently time consuming and costly. Patients and Methods We performed a cement embedding technique in 13 consecutive patients with infection after spinal instrumentation. After meticulous open débridement, the metallic implants were embedded using polymethylmethacrylate (PMMA) mixed with antibiotics. Antibiotics were selected in each case according to the pathogens and their sensitivity. The wound was primarily closed. We did not restrict the patients’ activity postoperatively. The implants were not removed unless it was necessary for further procedures. Results Nine patients, including those infected by methicillin-resistant Staphylococcus aureus (MRSA), were cured by débridement and PMMA embedding followed by systemic antibiotic treatment. No complications were reported. Conclusions The antibiotic-impregnated PMMA embedding technique is an effective method for the treatment of spinal instrumentation infections. It is easy to perform and is also effective for MRSA infection.
Introduction Spinal instrumentation is thought to be a risk factor for deep surgical site infection (SSI).1 When SSI occurs in patients with an instrumented spine, the management of the infection is more challenging compared with that for SSI without instrumentation. Although some authors have reported that a biofilm shows lower adhesion ability to titanium in comparison with stainless steel2 and modern titanium alloy implants are thought to have a reduced need for removal in case of infection, we are still confronted with devastating cases that cannot be treated conservatively. To avoid implant removal that could cause spinal instability, a wide variety of methods has been developed to achieve preservation of infected spinal
received October 23, 2013 accepted after revision November 15, 2013 published online June 27, 2014
Takahiro Goto1
implants. Historically early repetitive débridement was advocated as the optimal strategy for implant preservation.3,4 Currently, closed-suction irrigation system5–8 and vacuumassisted closure (VAC)9–14 are the two most commonly reported techniques. However, these methods still lead to longstanding restriction of activities of daily living (ADLs) for patients, necessitate human resources and is expensive. Therefore, simpler and more cost-effective methods of implant salvage are needed. Antibiotic-impregnated polymethylmethacrylate (PMMA) has been widely used in infections following joint replacement surgery.15,16 With regard to spine surgery, the use of PMMA beads for infected instrumentation was reported in 1990s.17 We developed a novel simple PMMA embedding
© 2014 Georg Thieme Verlag KG Stuttgart · New York
DOI http://dx.doi.org/ 10.1055/s-0034-1371519. ISSN 2193-6315.
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
So Kato1
Journal of Neurological Surgery—Part A
Vol. 75
F
M
62
68
62
63
72
68
57
35
49
63
50
3
4
No. A6/2014
5
6
7
8
9
10
11
12
13
L2 OCF, kyphosis
C6 metastasis
C4–C6 metastasis
C5–C6 pseudoarthrosis
T11–L1 osteosarcoma
None
Malignancy
Malignancy
None
DM, malignancy, CRF
DM, malignancy, CRF
RA
Malignancy
Steroid use
Steroid use
Malignancy
DM, malignancy
RA
Comorbidity
Multiple previous operations
Previous radiation therapy
Previous radiation therapy
Smoking
Multiple previous operations, previous radiation therapy
Multiple previous operations
Multiple previous operations
Multiple previous operations, previous radiation therapy
Other risk factors for SSI
L2 PSO, T11–L5 PSF
C4–C7 LN, C4–C7 PSF
C3–C7 LN, C2–T1 PSF
C5–C6 PSF
T10–12 LN, T9–L2 PSF
T12–L1 LN, T11–L3 PSF
L1–L2 PSO, T10–L4 PLF
T2–T4 LN, T1–T5 PSF
L1–L5 PLIF
L4–S1 PLF
T4–T7 LN, T2–L1 PSF
C1 LN, Occiput–C4 PSF
Occipt–C5 PSF
Initial operation
535
273
433
158
243
209
401
211
406
223
220
180
325
Length of initial operation, min
3270
1730
1340
290
380
130
790
230
700
290
1230
1020
235
Blood loss, mL during initial operation
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Abbreviations: CRF, chronic renal failure; DM, diabetes mellitus; LN, laminectomy; OCF, osteoporotic compression fracture; PLF, posterolateral fusion; PLIF, posterior lumbar interbody fusion; PSF, posterior spinal fusion; PSO, pedicle subtraction osteotomy; RA, rheumatoid arthritis; SAS, subaxial subluxation; SSI, surgical site infection.
F
M
M
L1 metastasis
L1–L2 OCF, kyphosis
T3 metastasis
L4 OCF
L5 OCF
T4–T12 metastasis
C1–C2 metastasis
C4–C5 SAS
Disease
Antibiotic-Impregnated Cement Embedding Technique
M
F
F
F
F
F
M
63
2
F
Sex
72
Age, y
1
Case
Table 1 Patient demographic data
480 Kato et al.
Antibiotic-Impregnated Cement Embedding Technique
Patients and Methods Among the patients who underwent instrumentation in our service between January 1995 and May 2011, 25 patients were diagnosed with deep SSI. We used the antibiotic-impregnated PMMA embedding technique for 13 consecutive patients (five men and eight women) beginning February 2004. ►Table 1 summarizes the demographic data of the patients. The diagnosis of SSI was confirmed by physical findings, laboratory data, and/or radiographic findings. The median time interval between the primary operation and the diagnosis of SSI was 8 days (range: 5–33 days). The pathogens and their sensitivity to antibiotics were identified by blood culture and stab culture of the infected wound. The pathogen was methicillin-resistant Staphylococcus epidermidis (MRSE) in six, methicillin-sensitive Staphylococcus aureus in three, methicillin-resistant Staphylococcus aureus (MRSA) in two and Enterobacter cloacae in two patients.
Surgical Technique Once the diagnosis of SSI was confirmed, the patient was transferred to the operating room for open débridement of all infected tissues. Large-volume irrigation using normal saline was performed. Implant loosening was ruled out. The PMMA powder was manually mixed with the antibiotic powder (typically 3.0 g of vancomycin per 20 g of PMMA); both were then meticulously mixed with the liquid monomer in the closed mixing bowl until the mixture became completely homogeneous. After the antibiotic-impregnated PMMA became moldable, the whole metallic surface was embedded (►Fig. 1). If the pathogen was not yet identified, vancomycin was empirically given. Otherwise, the antibiotic was selected according to the pathogen and its sensitivity: These antibiotics were included gentamicin, meropenem, and ceftriaxone. A closed suction drain was placed subfascially, and the wound was primarily closed. Intravenous antibiotics were administered for 6 weeks in most cases, followed by oral
481
antibiotics as needed. The drainage was removed within 7 days postoperatively. We did not restrict the patients’ activity after surgery. All patients were discharged after wound healing and normalization of C-reactive protein and erythrocyte sedimentation rate. The treatment was considered successful if laboratory data and clinical findings ruled out recurrence after the discontinuation of oral antibiotics.
Results ►Table 2 shows the details of SSI and subsequent treatment. One patient with spinal metastasis died of tumor progression unrelated to infection 9 weeks after the operation (case 9). In the other patients, the median follow-up period was 1.5 years (range: 3.8 months to 8.2 years). Nine patients were cured; postoperative spinal stability was confirmed radiographically. No complications attributable to the embedding technique were observed throughout the treatment course. In three patients, we failed to control the infection. One of them was cured by implant removal (case 5). In the other two with a history of radiation therapy for spinal metastasis (cases 3 and 8), we did not removed their implants due to concerns about stability because of massive vertebral invasion and switched to VAC treatment. However, the infections could not be controlled until their deaths. In summary, 10 of 13 patients were cured in terms of infection control, and 9 of these 10 cured patients (90%) were successfully treated with implant salvage. In comparison, before we established this antibiotic PMMA embedding technique, 10 of 12 patients were cured, but only 3 (30%) underwent standardized repetitive open débridement without implant removal.
Case Presentation (Case 13) A 50-year-old woman with lumbar kyphosis due to L2 osteoporotic compression fracture underwent L2 pedicle subtraction osteotomy in combination with T11–L5 posterior spinal fusion. Surgical procedure was successfully completed, but wound secretion did not cease and dehiscence subsequently occurred. She had a fever of 39°C on the eighth postoperative day, and stab culture showed gram-positive
Fig. 1 Scheme of antibiotic-impregnated polymethylmethacrylate (PMMA) embedding technique. (A) First operation: Posterior decompression and fusion. (B) Second operation for infection: PMMA embedding. Journal of Neurological Surgery—Part A
Vol. 75
No. A6/2014
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
technique for infected implants and have used this method since 2004. In the present case series, we report the outcomes and discuss its effectiveness.
Kato et al.
Journal of Neurological Surgery—Part A
63
62
68
62
63
72
68
57
35
49
63
50
2
3
Vol. 75
4
5
6
No. A6/2014
7
8
9
10
11
12
13
F
M
M
F
M
M
F
F
F
F
F
M
F
Sex
8
7
33
6
16
14
8
16
9
5
7
5
9
Time to infection, d
Wound secretion, wound dehiscence
Wound secretion, redness
Wound secretion, redness
Wound secretion, fever, pain
Wound secretion, wound dehiscence
Wound secretion, fever
Wound secretion, fever
Wound secretion, fever, redness
Wound secretion, fever
Pain
Wound secretion, redness
Fever, pain
Wound secretion, fever
Initial symptoms of infection
MRSA
MSSA
MRSE
MRSE
MRSA
E. cloacae
MSSA
E. cloacae
MSSA
MRSE
MRSE
MRSE
MRSE
Causative organism
8
34 29 10 14 10 17 11
VCM 4.0 g þ PMMA 30 g MEPM 2.0 g, CTRX 2.0 g þ PMMA 40 g VCM 4.0 g þ PMMA 20 g VCM 3.0 g þ PMMA 20 g VCM 2.0 g þ PMMA 20 g VCM 3.0 g þ PMMA 20 g VCM 4.0 g, MEPM 4.0 g þ PMMA 40 g
23
VCM 1.5 g þ PMMA 10 g 11
12
GM 420 mg þ PMMA 20 g
12
VCM 2.0 g þ PMMA 10 g VCM 3.0 g þ PMMA 20 g
MEPM 2.0 g þ PMMA 20 g
46
Total duration of systemic antibiotics, wk
VCM 3.5 g þ PMMA 20 g
Antibiotic used with PMMA embedding
Cured
Cured
Cured
Cured
N/A
Failed
Cured
Cured
Failed
Cured
Failed
Cured
Cured
Result of operation for SSI
None (death)
VAC
Implant removal
VAC
Salvage procedure
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Antibiotic-Impregnated Cement Embedding Technique
Abbreviations: CTRX, ceftriaxone; E. cloacae, Enterobacter cloacae; GM, gentamicin; MEPM, meropenem; MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; MSSA, methicillin-sensitive Staphylococcus aureus; PMMA, polymethylmethacrylate; VAC, vacuum-assisted closure; VCM, vancomycin. a Thirteen consecutive patients with instrumentation infection underwent the polymethylmethacrylate embedding technique.
72
Age, y
1
Case
Table 2 Details of surgical site infection and subsequent treatmenta
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cocci. We made the diagnosis of SSI. After meticulous open débridement, the antibiotic-impregnated PMMA embedding technique was performed. Vancomycin and meropenem were selected empirically to cover MRSA as well as gram-negative germs, and they were mixed with 40 g of PMMA. The intraoperative picture is shown in ►Fig. 2. Because the causative organism turned out to be MRSA postoperatively, intravenous administration of vancomycin was continued for 5 weeks, followed by oral administration of clindamycin and rifampicin for 6 weeks. The wound healing was uneventful, and all laboratory data normalized rapidly. The patient was followed 18 months without signs of recurrence.
Discussion We reported the treatment outcomes of patients with deep SSI after spinal instrumentation undergoing the antibioticimpregnated PMMA embedding technique. This technique can be easily performed with no complications. It was also effective for MRSA infection. We suggest that spine surgeons consider this technique a useful option. Two factors make the treatment of instrumentation infections challenging. First, the bacteria can adhere to the metallic surfaces of the instrumentation in case of SSI.18,19 The cluster of bacteria forms a self-produced polymer matrix (glycocalyx, also known as a biofilm) that protects them and confers a much higher tolerance to antibiotics.6 The minimal inhibitory concentration and minimal bactericidal concentration of antibiotics are considered to be 100- to 1000-fold higher. Second, implant removal to eradicate infection seems reasonable,20,21 but results in spinal instability restricting the patients ADLs or even requiring bed rest until the infection is successfully controlled and re-instrumentation can be performed. As an option for implant salvage, antibiotic-impregnated PMMA has been used to treat SSI, and many authors reported good results with infection control after joint replacement surgeries.15,16 The local concentration of antibiotics is maintained over a few weeks by release from the impregnated PMMA with minimal systemic toxicity.22 For infections after spinal instrumentation, Glassman et al first reported successful instrumentation salvage in 1996.17 They packed a chain of
antibiotic-impregnated PMMA beads into the gutter lateral to the instrumentation. This technique is easy to perform, but has the drawbacks that the cement beads create a large dead space due to their bulky profile and are prone to dislodgement into the spinal canal. In the present study, we avoid these drawbacks by embedding the implants in the antibioticimpregnated PMMA, making the whole complex low profile and minimizing the risk of dislodgement. Our technique does not require prolonged bed rest and re-surgery for PMMA removal. Among our successfully treated patients were some with MRSA infection, which is considered to be difficult to control without implant removal. Possibly, this is related to a much higher local concentration of the antibiotic than in other management protocols, because the antibiotic-impregnated PMMA directly cover the biofilm. Further studies are needed to investigate local pharmacodynamics of antibiotics released from impregnated PMMA to clarify the mechanism of its effectiveness.
Conclusion Antibiotic-impregnated PMMA embedding technique is an effective method for treating infections after spinal instrumentation without implant removal. It is easy to perform and could also be effective for MRSA infection. We suggest that spine surgeons consider this technique as the first-line treatment.
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HN, Garfin SR, Eismont FJ, Bell GR, Balderston RA, eds. RothmanSimeone The Spine. Philadelphia, PA: Elsevier Saunders; 2011: 1789–1803 2 Sheehan E, McKenna J, Mulhall KJ, Marks P, McCormack D. Adhesion of Staphylococcus to orthopaedic metals, an in vivo study. J Orthop Res 2004;22(1):39–43 3 Aydinli U, Karaeminoğullari O, Tişkaya K. Postoperative deep wound infection in instrumented spinal surgery. Acta Orthop Belg 1999;65(2):182–187 4 Weinstein MA, McCabe JP, Cammisa FP Jr. Postoperative spinal wound infection: a review of 2,391 consecutive index procedures. J Spinal Disord 2000;13(5):422–426 Journal of Neurological Surgery—Part A
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Fig. 2 Demonstrative case (case 13) in which the antibiotic-impregnated polymethylmethacrylate (PMMA) embedding technique was used. Right: cranial, left: caudal. (A) After débridement. (B) The whole implant was embedded in PMMA.
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