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ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 10  |  Page : 3340-3344  

Study of antibiotic efficacy of topical vancomycin powder in treatment of infected mandibular fractures and soft tissue surgical site infections


1 Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, King Georges Medical University, Lucknow, Uttar Pradesh, India
2 Department of Dentistry, Sub-Divisional Hospital, Bundu, Ranchi, Jharkhand, India
3 Department of Head and Neck Oncology, Homi Bhabha Cancer Hospital, Varanasi, Uttar Pradesh, India

Date of Submission20-Aug-2019
Date of Decision20-Aug-2019
Date of Acceptance10-Sep-2019
Date of Web Publication31-Oct-2019

Correspondence Address:
Dr. Deepak Passi
Department of Dentistry, Sub Divisional Hospital, Bundu, Ranchi, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_661_19

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  Abstract 


Aims and Objective: To study the antibiotic efficacy of topical vancomycin in infected mandibular fracture treatment and its effect in preventing surgical site infections. Materials and Methods: The study comprised of 100 subjects of infected mandibular fractures requiring open reduction and internal fixation, randomly categorized into two equal groups of 50 each, that is, vancomycin group (N = 50) treated for infected mandibular fractures with topical vancomycin powder used as adjunct and non-vancomycin group (N = 50). Clinical parameters like hospital stay, postoperative infections, postoperative fever, abnormal swelling, purulent discharge, and fistula formation at surgical site and radiographic healing was evaluated and compared between the groups. Results: Mean age of vancomycin group and non-vancomycin group was 32.5 and 33.2 years, respectively. Demographic factors of the patients like age, sex, and hospital stay (3 ± 0.5 days) did not show significant difference between two groups. Vancomycin group shows 1 hyperthermia, 2 abnormal swelling and discharge, whereas non-vancomycin group shows 6 hyperthermia, 5 postoperative abnormal swelling and discharge with statistically significant (P < 0.05). Culture sensitivity of discharged fluid shows staphylococcal + MRSA infection in two patients in vancomycin group and eight patients in non-vancomycin group. Bony healing in vancomycin group shows one patient had non-union and one had graft rejection, whereas five patients had non-union and graft rejection in non- vancomycin group. The comparative results were statistically significant (P < 0.05). Conclusion: From the result of our study we can conclude that routine use of vancomycin powder in surgical site as a surgical adjunct reduces the incidence of infections at surgical site when it is applied in addition to standard antibiotic prophylaxis. Topical application into a surgical wound also reduces the risk associated with parenteral administration of vancomycin.

Keywords: MRSA (Methicillin resistant Staphylococcus aureus), SSI (surgical site infections), systemic toxicity, vancomycin


How to cite this article:
Singh G, Passi D, Daga D, Manas A, Vignesh U, Bhave SM. Study of antibiotic efficacy of topical vancomycin powder in treatment of infected mandibular fractures and soft tissue surgical site infections. J Family Med Prim Care 2019;8:3340-4

How to cite this URL:
Singh G, Passi D, Daga D, Manas A, Vignesh U, Bhave SM. Study of antibiotic efficacy of topical vancomycin powder in treatment of infected mandibular fractures and soft tissue surgical site infections. J Family Med Prim Care [serial online] 2019 [cited 2019 Nov 21];8:3340-4. Available from: http://www.jfmpc.com/text.asp?2019/8/10/3340/270015




  Introduction Top


Infection is one of the most common complication in mandibular fractures. It may be due to negligence on account of patients or may be surgical site infection. Careful aseptic technique is necessary to prevent any surgical site infections. Various treatment modalities had been suggested in literature for management of infected mandibular fractures. The main goals include restoration of pretrauma form and function, elimination of infection and limitation of pain and disability. Prolonged MMF and external fixation was used in the past for management of infected mandibular fractures.[1] Current literature supports use of rigid fixation, debridement and use of rigid fixation with bone grafting. Thus, there is decreased need for MMF and less reliance on patient cooperation for favorable outcome.[2]

Surgical guidelines recommend antibiotic prophylaxis in open surgical procedures, especially in cases with implantation. Administration of local antibiotics in conjunction with parenteral antibiotics is gaining popularity among surgeons for reducing the incidence of infection at surgical site.

Topical application of vancomycin was widely used in orthopedic and neurosurgery for prevention of surgical site infection. Local administration of powdered antibiotics with the potential to deliver high doses of antibiotic at surgical with less systemic exposure and hence less adverse effects has gained attention in medical literature. Also in recent year an increase in MRSA infection has been noted. Thus topical vancomycin powder in infected mandibular fractures was used in this study with aim to compare the outcome in patients with infected mandibular fractures treated with rigid fixation with and without the adjunct of topical vancomycin powder.


  Materials and Methods Top


A total of 100 patients were included in this study. Ethical approval was obtained from the institutional ethical committee (Study has been approved from institutional ethical committee dates 22 may 2017). Informed consent from patients was taken. Patients were divided into two groups [Groups 1 and 2] with 50 patients in each group. Healthy men and women between 20 and 65 years with clinically proven infected cases of mandibular fractures requiring open reduction and internal fixation were included in study. Patients with previous history of infections at the surgical site, allergic to vancomycin, pathological fracture, patients with systemic diseases/immuno-compromised (hypertension, diabetes mellitus, respiratory and cardiovascular disease, patient on steroids, bony disorders, smoking habit, etc.) and patients failing to visit postoperative follow-up time of less than 6 month were excluded from the study. All patients were operated by same surgeon and followed up for minimum of 1 year duration.

Surgical procedure

In infected fractures with purulent discharge, specimen of pus was acquired and sent for culture and sensitivity. Empirical antibiotic was started preoperatively after specimen was sent. In all patients, extraoral approach was preferred. Fracture site was exposed. Thorough debridement of the area was done till bleeding bone ensues. Any infected tooth or tooth in the fracture line indicated for removal were extracted. Intraoral irrigation was done. Fracture site was reduced. Rigid fixation was done. Use of bone grafts was done depending on the case. Iliac crest graft was used in most of the cases. Holes were drilled with drill bit corresponding to the diameter of the core diameter of the screw. A minimum of three screw rule with three screws on either side of the fracture site were placed. 1 g of vancomycin powder was applied directly to the wound just prior to closure. Vancomycin powder was sprinkled liberally over the area and suctioning of the area avoided thereafter to soak the vancomycin powder in blood already present at the site. Closure was done by 3-0 vicryl and 4-0 nylon sutures. Patients were discharged on oral antibiotics and recalled at 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery and followed up for at least 1 year. In cases of graft placement closure of graft site was done. Postoperative instructions were given and patient was hospitalized for 2--3 days postoperative [Figure 1], [Figure 2], [Figure 3].
Figure 1: Preoperative clinical and radiological images

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Figure 2: Intraoperative images showing vancomycin powder sprinkled over surgical site

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Figure 3: Postoperative clinical and radiological images

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  Results Top


The patients group who underwent surgery and received intrawound vancomycin powder in addition to the standard antimicrobial prophylaxis was categorized as vancomycin group (n = 50) and other group who did not receive intrawound vancomycin powder was categorized as non-vancomycin group (n = 50).

Among the different age intervals, vancomycin group shows 15 patients are less than 25 years, 28 patients are the age groups between 26 and 50 years, and 7 patients are between 51 and 65 years of age group. Mean age of vancomycin group and non-vancomycin group was 32.5 and 33.2 years, respectively [Graph 1].



There are 40 men and 10 women patients in vancomycin group and 42 men and 8 women patients in non-vancomycin group. Demographic factors of patients did not show significant difference between two groups [Graph 2]. Patients of both the groups show the hospital stay of 3 ± 0.5 days and comparative results was not significant [Table 1].

Table 1: Showing demographic and operative data

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Clinical evaluation and healing

Both the groups were evaluated clinically for postoperative fever, abnormal swelling, any purulent discharge, and fistula formation at surgical site. Out of 50 patients, 1 patient shows hyperthermia and 6 patients in vancomycin and non-vancomycin group respectively. Two patients had abnormal swelling and discharge in vancomycin group and 5 had swelling and discharge in non-vancomycin group. Two patients in non-vancomycin group had chronic postoperative fistula which was managed by debridement and culture directed antibiotics. Culture sensitivity of discharged fluid shows staphylococcal + MRSA infection in two patients in vancomycin group and 8 patients in non-vancomycin group. The comparative results was statistically significant (P < 0.05) [Graph 3].



In late postoperative period, bony healing was assessed through radiographs and the result shows one patient had non-union and one had graft rejection in vancomycin group. In non-vancomycin group, 5 patients had non-union and graft rejection. The comparative results was statistically significant (P < 0.05) [Graph 4].




  Discussion Top


Surgical site infections (SSIs) are currently the most frequent hospital-acquired infections accounting for 31% of all infections among hospitalized patients.[3] SSIs are also one of the most common complications in operated cases of maxillofacial trauma especially mandibular fractures despite of use of prophylactic antibiotics.  Staphylococcus epidermidis Scientific Name Search Staphylococcus aureus are the common bacteria associated with SSIs and are resistance to antibiotics that bind penicillin-binding proteins. SSI is thought mainly to arise from wound contamination occurring from small inoculums during the operation. 103-105 bacteria may be necessary to initiate a bone infection, however 10 organisms may be sufficient in the presence of an implant to cause infection.[4]

Local administration of topical powdered antibiotics was first popularized in the late 1960s for prevention of wound infection in abdominal surgery prior to the existence of effective systemic prophylaxis.[5]

Topical antibiotics have also been applied locally in irrigation solutions, ointments, pastes, beads, sponges, and fleeces.[6] Local administration of powdered antibiotics is a potential method to deliver exceptionally high doses of antibiotic to the surgical site with less systemic exposure and adverse systemic effects. The vancomycin was first isolated by Eli Lilly from Streptomyces orientalis and was renamed vancomycin due to its ability to kill penicillin resistant Staphylococcus aureus. This glycopeptides is highly effective against gram-positive bacteria. It acts as a bactericidal agent against most gram-positive bacteria by inhibiting cell wall synthesis.[7]

The main aim of locally applied powdered antibiotics is to achieve substantially higher and long-lasting antibiotic concentrations at the surgical site without exposing the systemic circulation to toxic drug levels. This pharmacokinetics is based on studies evaluating both serum drug levels and surgical site levels excreted into surgical drains. After administration of 2 g of vancomycin, surgical site levels during the first day postoperatively reached nearly 1,500 mg/L and remained elevated above 100 mg/L through the third day. Serum levels were undetectable (<0.6 mg/L) in 80% of patients.[8] 1 g of vancomycin topically in pediatric spine patients, with surgical drain levels reaching above 400 mg/L and serum concentrations peaking at a mean of only 2.5 mg/L postoperatively.[9]

Vancomycin has been selected as prophylactic topical antibiotic of choice due to its cost-effectiveness, easy-to-use powdered form, and its effective broad coverage against organisms such as MRSA. Intrawound topical vancomycin powder is not readily absorbed into the systemic circulation, but rather stays in the wound and acts locally to prevent infection.

Systemic level of vancomycin is lower than 2.0 μg/mL required to cause systemic toxicity. This may be largely due to large molecular size of vancomycin, thus interrupting vancomycin from absorbed systematically. Study comparing vancomycin and control group which injected S. aureus into the wound after surgery and concluded that intrawound vancomycin concentration was high enough to defeat known staphylococcal infection.[10]

Persistent systemic exposure to sub-inhibitory levels of vancomycin may cause resistant strains. The development of vancomycin intermediate-resistant Staphylococcus was demonstrated in anin vitro model with persistent vancomycin exposure above 10 mg/L.[11] However, the emergence of vancomycin resistance has not been reported in studies on the use of topical vancomycin in spine surgery[12]

One of the main attention of local antibiotics is low systemic toxicity. 16 studies including 6,701 patients shows only 23 complications including culture-negative seromas, ototoxicity resulting in transient hearing loss, nephropathy, and super-therapeutic exposure. One case of circulatory collapse following an anaphylactic reaction to intrawound vancomycin has been reported.[13] Study shows topical vancomycin is safe for use in pediatric patients with no reported anaphylaxis, nephrotoxicity, red man syndrome, thrombophlebitis, or rash.[14]

Topical vancomycin and healing

In an experiment, the use of local vancomycin shows no significant effect on fracture healing at typical levels achieved with systemic therapy.[15] Concentrations (>2,000 mg/L) may be attained when using local antibiotics. Studies on osteoblast-like cells have demonstrated that concentrations of vancomycin below 1,000 mg/L had little or no detrimental effect, but concentrations of 10,000 mg/L caused osteoblast cell death.[16] The relative risk for pseudoarthrosis with the use of topical vancomycin in was shown to 0.87.[17] Different studies shows that there is no increased risk of wound dehiscence at surgical site with the use of topical vancomycin, although one study reported n increased dehiscence and herniation.[18],[19],[20],[21],[22]

Topical application of vancomycin powder over surface wounds and suturing sites can be good method in treatment of SSI at primary healthcare centres. Primary care centres, rural areas where MRSA infections prevails more, vancomycin continues to be the drug of choice for treating most MRSA infections caused by multidrug-resistant strains with low side effects.


  Conclusion Top


Vancomycin is a well-known antibiotic against gram-positive bacteria. Its topical use is well studied in spine surgery, orthopedic surgery, and cranial surgery to reduce SSIs. The result of our study also shows decreased SSIs with its topical use when it is applied in addition to standard antibiotic prophylaxis. Topical application into a surgical wound also reduces the risk associated with parenteral administration. Also, there is no data and observation that routine single-use vancomycin powder leads to antibiotic resistance. So we can conclude that routine use of vancomycin powder in surgical site as a surgical adjunct reduces the incidence of infections at surgical site. Small sample size was our main limitation of our study and it requires larger study samples in randomized controlled trials for conclusive results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Maloney PL, Lincoln RE, Coyne CP. A protocol for the management of compound mandibular fractures based on the time from injury to treatment. J Oral Maxillofac Surg 2001;59:879-84.  Back to cited text no. 1
    
2.
Prein J, Schmoker R. Treatment of infected fractures and pseudoarthrosis of the mandible. In: Spiessl B, editor. New Concepts in Maxillofacial Bone Surgery. New York: Springer; 1976. p. 169-74.  Back to cited text no. 2
    
3.
Ulu-Kilic A, Alp E, Cevahir F, Tucer B, Demiraslan H, Selçuklu A, et al. Economic evaluation of appropriate duration of antibiotic prophylaxis for prevention of neurosurgical infections in a middle-income country. Am J Infect Control 2015;43:44-7.  Back to cited text no. 3
    
4.
Lidwell OM, Lowbury EJ, Whyte W, Blowers R, Stanley SJ, Lowe D. Airborne contamination of wounds in joint replacement operations: The relationship to sepsis rates. J Hosp Infect 1983;4:111-31.  Back to cited text no. 4
    
5.
Huiras P, Logan JK, Papadopoulos S, Whitney D. Local antimicrobial administration for prophylaxis of surgical site infections. Pharmacotherapy 2012;32:1006-19.  Back to cited text no. 5
    
6.
Hanssen AD. Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop Relat Res 2005;91-6.  Back to cited text no. 6
    
7.
Levine DP. Vancomycin: A history. Clin Infect Dis 2006;42(Suppl 1):S5-12.  Back to cited text no. 7
    
8.
Sweet FA, Roh M, Sliva C. Intrawound application of vancomycin for prophylaxis in instrumented thoracolumbar fusions: Efficacy, drug levels, and patient outcomes. Spine 2011;36:2084-8.  Back to cited text no. 8
    
9.
Armaghani SJ, Menge TJ, Lovejoy SA, Mencio GA, Martus JE. Safety of topical vancomycin for pediatric spinal deformity: Nontoxic serum levels with supratherapeutic drain levels. Spine 2014;39:1683-7.  Back to cited text no. 9
    
10.
Zebala LP, Chuntarapas T, Kelly MP, Talcott M, Greco S, Riew KD. Intrawound vancomycin powder eradicates surgical wound contamination: Anin vivo rabbit study. J Bone Joint Surg Am 2014;96:46-51.  Back to cited text no. 10
    
11.
Tsuji BT, Rybak MJ, Lau KL, Sakoulas G. Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob Agents Chemother 2007;51:1089-91.  Back to cited text no. 11
    
12.
Ghobrial GM, Cadotte DW, Williams K, Fehlings MG, Harrop JS. Complications from the use of intrawound vancomycin in lumbar spinal surgery: A systematic review. Neurosurg Focus 2015;39:E11.  Back to cited text no. 12
    
13.
Mariappan R, Manninen P, Massicotte EM, Bhatia A. Circulatory collapse after topical application of vancomycin powder during spine surgery Case report. J Neurosurg Spine 2013;19:381-3.  Back to cited text no. 13
    
14.
Gans I, Dormans JP, Spiegel DA, Flynn JM, Sankar WN, Campbell RM, et al. Adjunctive vancomycin powder in pediatric spine surgery is safe. Spine 2013;38:1703-7.  Back to cited text no. 14
    
15.
Haleem AA, Rouse MS, Lewallen DG, Hanssen AD, Steckelberg JM, Patel R. Gentamicin and vancomycin do not impair experimental fracture healing. Clin Orthop Relat Res 2004;427:22-4.  Back to cited text no. 15
    
16.
Edin ML, Miclau T, Lester GE, Lindsey RW, Dahners LE. Effect of cefazolin and vancomycin on osteoblasts in vitro. Clin Orthop Relat Res 1996;333:245-51.  Back to cited text no. 16
    
17.
Alcalá-Cerra G, Paternina-Caicedo AJ, Moscote-Salazar LR, Gutiérrez-Paternina JJ, Niño-Hernández LM. Application of vancomycin powder into the wound during spine surgery: Systematic review and meta-analysis. Rev Esp Cir Ortop Traumatol 2014;58:182-91.  Back to cited text no. 17
    
18.
Raahave D, Hesselfeldt P, Pedersen T, Zachariassen A, Kann D, Hansen OH. No effect of topical ampicillin prophylaxis in elective operations of the colon or rectum. Surg Gynecol Obstet 1989;168:112-4.  Back to cited text no. 18
    
19.
Andersen B, Korner B, Ostergaard AH. Topical ampicillin against wound infection after colorectal surgery. Ann Surg 1972;176:129-32.  Back to cited text no. 19
    
20.
Mohammed S, Pisimisis GT, Daram SP, Bechara CF, Barshes NR, Lin PH, et al. Impact of intraoperative administration of local vancomycin on inguinal wound complications. J Vasc Surg 2013;57:1079-83.  Back to cited text no. 20
    
21.
He Y, Liu Q, Wang Y, Zhao Y. The value of topical vancomycin powder prophylaxis in spinal surgical site infection with a focus on bacterial spectrum: A systematic review. Int J Clin Exp Med 2018;11:12933-45.  Back to cited text no. 21
    
22.
Tailaiti A, Shang J, Shan S, Muheremu A. Effect of intrawound vancomycin application in spinal surgery on the incidence of surgical site infection: A meta-analysis. Ther Clin Risk Manag 2018;14:2149-59.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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