Abstract
Background: The use of an effective antimicrobial preoperative skin preparation solution is essential in preventing infections after surgery, but the findings in the literature regarding efficacy are not necessarily applicable to surgery involving the hip. The purpose of the present study was twofold: 1) to examine the native bacteria on the skin at the hip and 2) to determine the efficacy of 2 surgical skin preparation solutions at eliminating bacteria from the hip site in patients undergoing total hip arthroplasty.
Methods: We conducted a prospective randomized controlled trial in consecutive adult patients who underwent primary total hip arthroplasty at a single institution from October 2014 to December 2015. Each patient was randomly allocated to be treated with 1 of 2 commonly used surgical skin preparation solutions: ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol) or DuraPrep (0.7% iodophor and 74% isopropyl alcohol). Aerobic and anaerobic samples were obtained for culture before skin preparation, immediately after skin preparation and after skin closure.
Results: Full data were obtained for 105 patients: 54 in the ChloraPrep group and 51 in the DuraPrep group. Staphylococcus epidermidis, Corynebacterium and Micrococcus luteus were the organisms most commonly isolated from the hip before skin preparation. Positive bacterial culture results were obtained in 50 patients (93%) in the ChloraPrep group and 48 patients (94%) in the DuraPrep group. Immediately after skin preparation, the overall proportion of positive culture results was significantly lower in the DuraPrep group than the ChloraPrep group (14% v. 35%, adjusted relative risk 0.40, 95% confidence interval 0.18–0.85). After wound closure, there was no significant difference in the rate of positive culture results between the 2 groups.
Conclusion: DuraPrep was more effective than ChloraPrep at eliminating skin flora at the hip initially on application, but the 2 solutions were equally effective at the time of closure. Further study with larger samples is required to identify any influence of skin preparation solution on the incidence of prosthetic joint infection.
Postoperative infections are relatively uncommon after arthroplasty, with reported rates ranging between 0.25% and 2.0%.1 When postoperative infections do occur, they can lead to considerable patient morbidity and cost.2,3 A potential risk factor for the development of postoperative wound infection is the amount of bacterial skin flora present at the operative site at the time of surgery. Human skin is home to a diverse community of microorganisms. Therefore, it is critical to use an effective antimicrobial preoperative skin preparation solution to prevent contamination at the surgical site and, in turn, the surgical wound.
Several different types of antimicrobial skin preparation solutions are currently available. Guidelines published by the Centers for Disease Control and Prevention and the World Health Organization state that alcohol-based preparations combining chlorhexidine or iodophors with alcohol are recommended in preference to aqueous-based solutions.4,5 However, these guidelines do not provide consensus regarding which agent to combine with alcohol, and, thus, controversy still exists as to which solution is superior.
Several authors have investigated bacterial cultures before and after skin preparation for orthopedic surgery; however, the procedures were performed on the foot, shoulder, lumbar spine, knee or hand.6–10 The topography of the hip is quite different from that of other sites, and different native bacterial flora likely reside in this region.11,12 In addition, the hip is adjacent to several distinct areas, including the inguinal fold, buttock and perineum. Thus, the findings in the literature are not necessarily applicable to surgery involving the hip.
The purpose of this study was twofold: to examine the native bacteria present on the skin around the hip, and to assess the efficacy of 2 of the most commonly used surgical skin preparation solutions, ChloraPrep (chlorhexidine–alcohol) and DuraPrep (iodine–alcohol), at eliminating bacteria from the hip site.
Methods
Study design and participants
This prospective randomized trial included consecutive adult patients who underwent elective primary total hip arthroplasty at a single institution from October 2014 to December 2015. A 3-month moratorium (July–September 2015) was imposed on the study owing to limitations of supply of the neutralization agent. All procedures were performed by 1 of 3 fellowship-trained arthroplasty surgeons (K.P.D., D.P., C.C.) using the lateral or posterior approach. Research ethics board approval was obtained from the institution. All patients gave informed consent to participate in the study and were required to be able to communicate in English.
Patients were formally interviewed by a clinical trials nurse to obtain information about confounding variables such as smoking history and chronic disease, including diabetes. Patients were excluded if they had had previous hip surgery, had evidence of an abrasion or open wound at the incision site, had an active infection at or near the incision site or elsewhere in the body, or were chronically immunosuppressed.
All patients were seen at 6 weeks and 3 months postoperatively to evaluate for any wound complications.
Skin preparation
Hair within the surgical region was removed with clippers just before surgery. No antimicrobial bathing cleanser was used preoperatively. Perioperative antibiotics were given to all patients (1 or 2 g of cefazolin, depending on weight, within 1 h of surgery; if allergic to penicillin, they received 600 or 900 mg of clindamycin, depending on weight). No antimicrobial adhesive drape was used for any of the procedures.
Immediately before surgery, patients were randomly assigned to receive 1 of 2 commonly used surgical skin preparation agents: ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol; Enturia) or Dura-Prep (0.7% iodophor and 74% isopropyl alcohol; 3M Healthcare). Randomization, with an allocation ratio of 1:1, was performed by a clinical trial nurse by opening a sealed envelope that indicated the agent to be used. Each hip region was then prepared according to the manufacturer’s instructions by trained operating room staff and allowed to dry. Patients and surgeons were not blind to treatment group; however, culture specimens did not identify which treatment group the participant belonged to in order to blind those performing the laboratory analysis and reporting the results of bacterial culture.
Sampling and culture
All patients had culture specimens obtained before skin preparation, after skin preparation and immediately after skin closure. Both aerobic and anaerobic cultures were done; therefore, 6 specimens were obtained for each patient. All culture specimens were collected with premoistened, sterile rayon-tipped swabs (aerobic: Copan Diagnostics; anaerobic: Starplex Scientific). A validated neutralization agent was used to ensure that the antimicrobial activity of the skin preparation solution was stopped immediately upon sampling. The specimens obtained before skin preparation were premoistened with sterile saline, and those obtained after skin preparation and after skin closure were premoistened with neutralization agent, since these were the samples that incorporated the skin preparation agent.
A 4 cm × 4 cm area adjacent to the proposed incision site was sampled before preparation. Once the skin was prepared with agent, the square was divided in half; one half was used for sampling after skin preparation, and the other half for sampling after skin closure. This ensured that neutralization solution would not be applied to the postclosure section before sampling. Swab sampling was performed by the surgeon with a firm motion for a minimum of 10 seconds on the skin. The swab was placed in a sterile container and immediately transported to the microbiology laboratory at our hospital.
All cultures were incubated for 7 days. Swab samples of neutralization agent were analyzed weekly and served as negative controls. Neutralization agent was supplied by an independent laboratory (MicroBioTests) not affiliated with the study. Details of the neutralization agent have been previously described.8
Statistical analysis
Sample size requirements were based on the findings of a prospective randomized study evaluating the rate of positive results of culture of specimens from the shoulder after skin preparation.7 On the basis of the assumption that a 20% difference in positive culture rates would be clinically relevant, the number of participants required to achieve 80% power at α = 0.05 would be at least 50 per group. We used descriptive statistics (means and proportions) to present baseline patient characteristics including age, sex, body mass index, and proportions of smokers, patients with diabetes and patients diagnosed with rheumatoid arthritis. We presented proportions of positive culture results overall and for the most common bacteria for the prepreparation, postpreparation and postclosure stages. We computed the relative risk (RR) of a positive culture result for the 2 skin preparation solution groups by time (after surgical skin preparation and after skin closure) using a generalized linear model. Within the model, we adjusted for patient characteristics (age, sex, body mass index), duration of surgery and culture result (positive or negative) at prepreparation. For the most common bacteria, we calculated RRs comparing group by time (after skin preparation and after skin closure). We also examined percent reduction and associated RR of the most common bacteria by group by time (before v. after skin preparation; after skin closure v. after skin preparation). Significance was defined as p < 0.05.
Results
Between October 2014 and December 2015, 347 patients consented for total hip arthroplasty. Of the 347, 115 were enrolled in the study (Figure 1). Ten patients were excluded after randomization; reasons for exclusion were no neutralization agent available (n = 5), use of a contaminated neutralization agent (negative control for the lot returned with a positive result) resulting in a spurious microbiologic profile (n = 3), antimicrobial skin wash used (n = 1) and withdrawal from study before surgery (n = 1) (Figure 1). The trial ended when the last follow-up visit was completed, in May 2016. Full data were obtained for 105 patients: 54 in the ChloraPrep group and 51 in the DuraPrep group.
Flow diagram showing patient allocation.
The study included 58 male and 47 female patients with an average age of 65.8 (range 36–86) years, average body mass index of 29.9 (range 27.1–47.1) and average duration of surgery of 60 (range 23–103) minutes. Twelve patients (11.4%) were active smokers, 18 (17.1%) had diabetes, and 10 (9.5%) had been diagnosed with rheumatoid arthritis. The 2 groups were similar across patient characteristics (Table 1).
Baseline characteristics of patients who underwent total hip arthroplasty, by surgical skin preparation solution
Culture results
Culture of specimens obtained before surgical skin preparation gave positive results in 50 (93%) and 48 (94%) of patients allocated to the ChloraPrep and DuraPrep groups, respectively (Table 2). The most common bacterial organisms isolated were Staphylococcus epidermidis (50 isolates), Corynebacterium (47 isolates), Micrococcus luteus (40 isolates), S. hominis (38 isolates) and S. capitis (22 isolates) (Figure 2). Propionibacterium acnes was cultured in 5 isolates. A mean of 3.4 different organisms were isolated from the site. Two or more isolates were obtained in 76 patients (72.4%), and 3 or more were identified in 66 (62.8%). Corynebacterium was present in 32 patients (63%) in the DuraPrep group, compared to 17 (31%) in the ChloraPrep group. No other differences in organism distribution were identified between the 2 groups.
Bacterial culture results.
Overall positive culture results
Immediately after skin preparation, the overall proportion of positive culture results was significantly lower in the DuraPrep group than in the ChloraPrep group (14% [n = 7] v. 35% [n = 19], adjusted RR 0.40, 95% confidence interval [CI] 0.18–0.85) (Table 2). The most common bacterial organisms isolated at this stage were M. luteus (15 isolates), Corynebacterium (4 isolates) and S. epidermidis (3 isolates) (Figure 2).
After wound closure, there was no significant difference in the positive culture rate between the DuraPrep and ChloraPrep groups (29% [n = 15] v. 35% [n = 19], adjusted RR 0.83, 95% CI 0.48–1.44). There was a 114% increase in the proportion of positive culture results after wound closure compared to immediately after skin preparation in the DuraPrep group (adjusted RR 2.10, 95% CI 1.12–3.95). The most common bacterial organisms isolated after wound closure were M. luteus (15 isolates), Staphylococcus (5 isolates) and Corynebacterium (3 isolates) (Figure 2).
The rates of positive culture results for the most common organisms are shown in Table 3. After skin preparation, 14 specimens (26%) in the ChloraPrep group and 1 specimen (2%) in the DuraPrep group yielded M. luteus (adjusted RR 0.08, 95% CI 0.01–0.55). Similar proportions were seen after closure (24% v. 4%, adjusted RR 0.16, 95% CI 0.04–0.69). There was a greater reduction in the proportion of cultures positive for M. luteus in the DuraPrep group than in the Chlora-Prep group after skin preparation (95% v. 21%, adjusted RR 0.06, 95% CI 0.01–0.43) and after closure (91% v. 27%, adjusted RR 0.13, 95% CI 0.03–0.55). No differences were observed after skin preparation for the other common organisms between the 2 groups.
Positive culture results for common bacteria, by time and group
Association with confounding variables/ complications
Male patients had an 85% increased risk of a positive culture result overall compared to female patients (adjusted RR 1.85, 95% CI 1.05–3.24). Age (p = 0.6), body mass index (p = 0.8), positive culture result before skin preparation (p = 0.2) and duration of surgery (p = 0.8) were not significantly associated with increased risk of positive culture results.
Three patients had superficial wound complications within 6 weeks of surgery, 1 (2%) in the ChloraPrep group and 2 (4%) in the DuraPrep group (p = 0.6). No superficial wound complications were identified at 3 months, and no deep wound infections were encountered during the duration of the study.
Discussion
We found that the most common bacteria cultured from the hip area in patients undergoing total hip arthroplasty were S. epidermidis (48% of samples), Corynebacterium (45%), M. luteus (38%), S. hominis (36%) and S. capitis (21%). Collectively, coagulase-negative Staphylococcus was the most prevalent organism. In contrast to reports evaluating the bacteria around the shoulder, lumbar spine and hand,7,8,10 there was a paucity of P. acnes at the hip.
In a recent randomized controlled trial (RCT) comparing alcohol-based skin preparations after hip and knee arthroplasty, no difference was observed in the incidence of superficial wound complications.13 However, in an analysis of secondary outcomes, a significant difference was found in favour of iodine–alcohol for the prevention of surgical site infections (SSIs).13 The rate of SSIs was 1.0% and 3.1% in the alcohol and chlorhexidine groups, respectively (OR 3.06, 95% CI 1.26–7.46). These results are in contrast to the World Health Organization guidelines, which recommend that chlorhexidine-based preparations be used.5
In several recent meta-analyses, investigators aimed to evaluate the efficacy of chlorhexidine- and iodine-based alcohol solutions for the prevention of SSI after surgery. Based on 9 RCTs, Privitera and colleagues14 reported in favour of chlorhexidine (RR 0.70, 95% CI 0.52–0.92). Chen and colleagues15 examined 19 RCTs and reported a lower SSI rate with chlorhexidine than with povidone–iodine (RR 0.57, 95% CI 0.47–0.70). Although these results are promising, they should be interpreted with caution, as the formulation, concentration and application of the antiseptic solutions were variable and not consistent across studies. Furthermore, a range of procedure types were included, with limited data from orthopedic studies. A meta-analysis based on 13 RCTs showed an overall reduction in the risk of SSI with the use of chlorhexidine compared to iodine (RR 0.79, 95% CI 0.67–0.93); however, in a subgroup analysis examining only bone and joint data (5 RCTs), chlorhexidine was associated with an increased risk of SSI (RR 2.67, 95% CI 1.05–6.8).16 Thus, the efficacy of antiseptic solutions may differ according to the surgical procedure.
Since the incidence of SSI is very low after hip arthroplasty,1 most studies assessing colonization or culture rates (including the present study) are underpowered to detect differences in SSI rates between skin preparations. However, they are powered to detect differences in the reduction of skin flora, which may serve as a potential surrogate measure of efficacy. Ostrander and colleagues6 and Saltzman and colleagues7 concluded that ChloraPrep was at least twice as effective as DuraPrep in eliminating bacteria from the forefoot and shoulder regions, respectively. Neither group used a neutralization agent before sampling. Contamination with antiseptic on the culture swab likely led to ongoing bacterial death and exaggerated efficacy, particularly in the ChloraPrep group, as it is a non–film-forming antiseptic.17 Savage and colleagues8 reported that ChloraPrep and DuraPrep were equally effective at eradicating bacteria on the skin overlying the lumbar spine region. Although they used a neutralization agent, they reported a relatively low prepreparation positive culture rate of 82%, which suggests that the sampling technique or the laboratory plating process was not ideal, and, as a result, culture results after skin preparation were under-represented. In a study evaluating the flora on the hand, Xu and colleagues10 reported that the rate of positive culture results after skin preparation was 26% in the Chlora-Prep group, 4% in the DuraPrep group and 1% in the Betadine group (p < 0.001). They, too, had a low prepreparation rate of positive culture results, 38%, and did not control for antimicrobial hand washing by the patients before surgery. Consequently, it remains unclear whether a specific solution is superior.
The rate of positive culture results before skin preparation in the current study (93% in the ChloraPrep group and 94% in the DuraPrep group) suggests a more robust sampling and culturing process than in the previous studies. Furthermore, presurgical cleansing soap and adhesive sealant drapes were not used in order to eliminate any potential confounding effects. DuraPrep was more effective than ChloraPrep at eradicating bacteria initially on application. However, there was no difference between the preparation solutions after wound closure. This initial difference was largely due to the continued presence of M. luteus in the ChloraPrep group. Continued presence of Micrococcus was also observed on the skin overlying the lumbar spine, as Savage and colleagues8 reported a reduction of only 30% of Micrococcus isolates after skin preparation. The clinical significance of this finding is unclear, as periprosthetic infections from M. luteus are relatively rare.18
Limitations
This study was not powered to show a correlation between prosthetic joint infection and type of skin preparation solution. The rate of prosthetic joint infection in elective total hip arthroplasty is very low.1 The overall rate of superficial and deep wound infection in our study was 3% and 0%, respectively. A much larger patient population would be required to show a significant correlation. Second, qualitative rather than quantitative culture data were used. Perhaps the number of residual colonies is more representative of solution efficacy and, in turn, the risk of postoperative infection. Last, contamination was encountered, which resulted in 3 false-positive results; the data from the affected patients were excluded.
Conclusion
This study successfully identified the native bacteria present on the skin around the hip. In addition, DuraPrep was more effective than ChloraPrep at reducing bacteria at the hip immediately after skin preparation for surgery. At the time of wound closure, there was no longer a difference between the 2 solutions. Further study with larger samples is required to identify any influence of skin preparation solution on the incidence of prosthetic joint infection.
Acknowledgements
The authors thank Lori Moon for assistance with participant recruitment and consent; Simrun Chahal and Paige Wagar for assistance with the manuscript submission and revision process; Rabail Siddiqui for assistance with data cleaning; Shalyn Littlefield for assistance with writing and submitting grant applications that made the project possible, protocol development and data management; and Wendy Goliquer for assistance with sample analysis and management.
Footnotes
Competing interests: None declared.
Contributors: K. Droll, M. Abouassaly, C. Cullinan and D. Puskas designed the study. S. Dubois analyzed the data. K. Droll wrote the manuscript, which M. Abouassaly, C. Cullinan, D. Puskas and S. Dubois critically revised. All authors gave final approval of the article to be published.
Data sharing: Data are available on request from the corresponding author.
Funding: This study was supported by a Northern Ontario Academic Medicine Association Clinical Innovation Opportunities Fund grant to Kurt Droll.
- Accepted January 29, 2022.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
References
In this issue
Article tools
Related Articles
Cited By...
- No citing articles found.