INTRODUCTION
Despite the use of prophylactic systemic antibiotics and improved surgical techniques, surgical site infection (SSI) is still a serious, challenging postoperative complication. Such infections often require additional surgery, prolonged administration of systemic antibiotics, delayed rehabilitation, and increased medical costs. Therefore, they have a profound impact on patients. In addition, mortality risk is doubled in patients with SSI12).
To reduce the incidence of infection, local application of antibiotics is an attractive option because high concentrations are achieved directly at these sites and systemic toxicity is limited6,7,14). In the only human study of prophylactic local antibiotics, the addition of vancomycin powder to standard systemic prophylaxis in elective spine surgery reduced infection rates from 2.6% to 0.2%27). In addition, no specific adverse events were reported, and no differences in radiographic outcomes was found between groups5,27).
The authors aimed to determine the effect of local application of vancomycin powder on reducing the infection rate among patients undergoing instrumented posterior spinal fusion, by comparing patients who did and did not receive local application of vancomycin powder at the surgical site, in addition to standard intravenous (IV) antibiotic prophylaxis.
MATERIALS AND METHODS
Study setting and Patient Enrollment
From July 2012 to December 2012, 74 consecutive cervical, thoracic, and lumbar instrumented spinal fusions were performed by 1 surgeon at a single institute.
From July 2012 to October 2012, all patients received standard systemic antibiotic prophylaxis consisting of 1 g IV cefazolin within 1 hour of surgical incision followed by 1 g IV cefazolin every 8 hours for 1 day. All patients who underwent spinal instrumented fusion surgery in or after October 2012 received an additional application of 1 g of vancomycin powder spread throughout the surgical wound.
Patients who had undergone elective spinal fusion using pedicle screw and rod instrumentation at any level for treatment of spinal instability were included. Patients with a previous history of spinal instrumented surgery and infections at the surgical site were excluded.
We divided the patients into 2 groups depending on the use of local application of 1 g vancomycin powder: Group A (additional local vancomycin powder used) and Group B (local vancomycin powder not used).
All patients underwent preoperative preparation with alcohol followed by betadine solution.
Before closing the wound, 1 g of vancomycin powder was directly applied on the muscle, fascia, and subcutaneous tissues after ensuring that the bone graft or dura mater was not exposed.
The wounds were closed with absorbable sutures for the fascia and subcutaneous layers and with staples for the skin. After skin closure, the incisions were cleaned again with alcohol and betadine solution, and a sterile dressing was applied.
A drain was kept in place until the drainage volume was less than 30 cc, and the dressing was maintained daily until the stitches were removed (usually 7 days).
The clinical demographics (age and gender), data on coexisting chronic diseases (diabetes, hypertension, and tuberculosis), history of tobacco use, and operative time for each patient were retrospectively obtained from clinical chart reports. The estimated blood loss (EBL), number of levels fused, and drain maintenance period were also obtained from the operative chart.
The primary outcome was the incidence of SSI. We classified SSI according to 2 types: deep SSI and superficial SSI. Deep SSI was confirmed by culture results of the drainage line tip, and superficial SSI was confirmed by the results of swab culture of surgical wound discharge. When SSI was discovered in a patient, cultured organisms and subsequent treatments were recorded.
Statistical Analysis
All retrieved data were converted into categorical or binominal variables. Chi squared test, 1-way analysis of variance (ANOVA), logistic regression analysis, multiple regression analysis, t-test, and Cox regression analysis were used for assessment of statistical relationships. Statistical significance was accepted at a p-value of <0.05.
RESULTS
Seventy-four patients were included in the study. Group A included 34 patients, and group B included 40 patients. Overall, the groups were similar with regard to baseline characteristics (Table 1). The general surgical variables between the 2 groups are described in Table 2. The operative level, approach methods, disease entity, and operative parameters (operation time, EBL, transfusion volume, and duration of drainage) of the 2 groups were similar, and no statistical differences were found between the 2 groups, except for infection rate. No infections (0%) occurred in group A, whereas 5 surgical infections (12.5%), including 3 deep wound and 2 superficial wound infections occurred in group B; this difference was found to be statistically significant (p=0.033) using Fisher's exact test. An additional statistical analysis for relative risk (RR) is shown in Table 3. This analysis revealed that the RR for infection in the control group was 1.143 times higher than that in the vancomycin group, which was found to be statistically significant (95% confidence interval, 1.017-1.285).
All SSIs were found in cases of posterior approach surgery, but this was not statistically significant (p=0.176). Methicillin-resistant coagulase-negative staphylococcus (MRCNS) was cultured from 2 of the 3 deep SSIs, and Acinetobacter baumannii was cultured from the third SSI. Two cases of methicillin-sensitive Staphylococcus aureus (MSSA) were found in the superficial SSIs. All SSIs occurred primarily in elderly patients. In our study, in contrast to common conventions, diabetes (p=0.178) and smoking history (p=0.147) were not associated with the occurrence of infection. Treatments used for patients with SSIs are described in Table 4.
No adverse effects were attributable to local application of vancomycin powder.
DISCUSSION
Postoperative deep wound infection after instrumented spinal fusion is a significant complication with an unexpected worsening clinical outcome. Prophylaxis with IV cephalosporin provides coverage for less than 50% of the Staphylococcus organisms found in hospitals and is probably not an adequate prophylactic agent by itself13,19). However, IV vancomycin does not reduce SSI rates either18,25), and administration of IV vancomycin is associated with several side effects, including hypotension, renal toxicity, and the development of resistant organisms17).
To reduce the rate of infection, the use of local antibiotics in addition to IV antibiotics has been suggested1,2,3,4,23,24). Local delivery of antibiotics is an attractive option because high concentrations are achieved directly at surgical wound sites and systemic toxicity is limited6,7,14). Thus, antibiotics are delivered where they are needed the most. This rationale is well accepted in the treatment of established infections and has recently been investigated as a means of prophylaxis rather than treatment.
Several related studies have reported the pharmacokinetics of locally applied antibiotic powder; however, the standard goal of local pharmacokinetics remains undetermined. In 2011, Sweet et al. reported the local pharmacokinetics of vancomycin powder27). Their study showed that very high doses of vancomycin were achieved in the local environment, with drug levels up to a 1,000-fold higher than the mean inhibitory concentration for methicillin-resistant S. aureus and coagulase-negative staphylococcus. Local application of vancomycin powder into the surgical wound produced wound drug levels of 128-1,457 µg/mL, several fold higher than those documented with vancomycin elution from bone cement (15 µg/mL). This concentration of vancomycin may provide a super-bactericidal effect in the local environment.
Several studies have reported the effect of local antibiotic powder. Kevin et al. reported a significantly lower incidence of postoperative surgical wound infections through the use of local vancomycin powder in patients undergoing posterior spinal stabilization for traumatic injuries20). The infection rate of 13% in the control group is in agreement with previous studies in this population22). No infections were found in the group treated with vancomycin powder in the surgical wound. This infection rate is consistent with that reported in a previous study of locally applied vancomycin powder for infection prophylaxis, which found that the infection rate decreased from 2.6% to 0.2% in patients undergoing elective spinal fusions27). Similarly, results of our study show a significant difference between the treatment (vancomycin powder) and control groups. There was no occurrence of infection in the treatment group, whereas 5 infections (12.5%) occurred in the control group. The group with local vancomycin powder treatment showed no infections, which was statistically different when compared with the infection rate in the group with no use of local vancomycin powder (p=0.033).
Some studies have reported that high concentrations of antibiotics inhibit bone healing in vitro5,8-11,16,15,21). In an animal model, the peak concentration of gentamicin after application of powder briefly exceeds the threshold for affecting osteoblasts10,26). However, it is unclear whether this would have a significant effect on bone healing or fusion. In the only human study of prophylactic vancomycin powder usage, concentrations were found to be well below the threshold concentration estimated to inhibit osteoblasts in vitro, and no difference was found in radiographic outcomes2,5,27).
This study has several limitations. First, this study was conducted in a retrospective fashion. Therefore, selective bias and confounding factors were likely present. In addition, not all factors known to contribute to postoperative infections were evaluated. Information on factors that contribute to infection, such as limited mobility, malnutrition, obesity, and various medical comorbidities could not be obtained in a retrospective fashion. The available data were insufficient for comparison of nutrition markers. Another limitation is that a relatively small number of patients were evaluated. Finally, the local pharmacokinetics (such as the local concentration and dose) achieved using the method described in our study remains undetermined. Future studies are needed to determine the minimally effective local concentration and to standardize the treatment dose of vancomycin.
CONCLUSION
In our study, the use of local vancomycin powder resulted in a significant decrease in the occurrence of postoperative infections in patients undergoing instrumented spinal fusion surgery. No adverse side effects were attributable to the local vancomycin powder. Additional prospective and large-volume studies are needed to further substantiate the effectiveness of this prophylactic method for reduction of postoperative spinal SSIs using a simple application of local vancomycin powder. Furthermore, culture of the drainage tip is very important for confirming the microorganisms present in deep wound infection; the results of culture facilitate selection of antibiotic treatment for postoperative infections.
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