Microbiology and Risk Factors of Surgical Site Infection in Limb Fractures


 Background: Limb fractures are becoming more common, and implant implants increase the risk of surgical site infection.The purpose of this study was to identify risk factors and microbiological characteristics for surgical site infection of limb fractures.Methods: We reviewed the data of 4,478 patients with limb fractures treated at Zhejiang Provincial People's Hospital from January 2010 to January 2020, including demographic, fracture, and microbiological characteristics. Chi-square tests and multivariate logistic regression were used to identify risk factors.Results: Staphylococcus aureus is a major threat to surgical site infection of limb fractures (26.46%). Open fractures are a risk factor for gram-negative infections. The following factors are considered as risk factors for surgical site infection: lower limb fractures, diabetes mellitus (OR 2.911 ; 95% CI 1.767-4.793), hypoproteinemia (OR 5.153 ; 95% CI 2.478-10.714), vascular injury(OR 8.531 ; 95% CI 4.028-18.070), nerve injury(OR 1.966 ; 95% CI 1.132-3.414) and open fractures (OR 9.561 ; 95% CI 6.565-13.925).Conclusions: Patients with these factors are at risk of surgical site infection after open reduction and internal fixation, and orthopedic surgeons should pay attention to these patients.


Introduction
Limb bones are more vulnerable to the violence that causes fractures than axial and skull bones. In recent years, the treatment of limb fractures has been improving, for example, by designing longer steel plates and intramedullary nails, and improving the coating of internal plant surfaces to reduce complications such as osteoporosis, nonunion, and posttraumatic bone defects. [1] However, post-implantation infection is still an important problem for orthopedic surgeons.
Deep surgical stie infection (SSI) is de ned as an infection that occurs in the fascia, muscle layer, or any part of the body that is opened during surgery. On average, SSI extended hospital stays by 9.7 days and increased the cost of each hospitalization by $20,000. [2] Orthopaedic surgery poses a greater risk of infection than other procedures without implant implants. Microorganisms commonly associated with orthopedic SSI, such as Staphylococcus aureus (S. aureus) and Staphylococcus epidermis (S. epidermis), can adhere to the surface of internal plants and form bio lms to resist the in ltration of antibiotics. [3] At the same time, the presence of implant tends to make the infection more chronic, stimulating the formation of granulation tissue and the formation of brous encapsulation. [4] Identi ed the microbiological characteristics of different limb fractures and risk factors for SSI is important to infection prevention. Continuous infection surveillance has been used worldwide for infection prevention. [5] In this study, we evaluate the microbiological characteristics and incidence of SSI for limb fractures and to identify risk factors.

Methods
We reviewed the data of patients with limb fractures who underwent surgery at Zhejiang Provincial People's Hospital from January 1, 2010 to January 1, 2020. This 1800-bed university a liated hospital, with a 219-bed Orthopedic Service, served a total population of about 1000,000 people.
We accessed the database of hospital and screened out 4478 patients meeting the inclusion. Next, four physicians recorded data of each patients, including gender, age, hypertension, diabetes, hypoproteinemia, nerve injury at the fracture site, vascular injury at the fracture site, skin injury, wound type, infections, infecting microorganisms and drug sensitivity test results.
SSI was de ned according to a standard 2008 Centers for Disease Control and Prevention (CDC) de nition. [6] The infection occurring within 1 year after implantation was de ned as SSI. All SSIs detected during hospitalisation, readmission and post-discharge outpatient visit were included.
Potential risk factors associated with SSI were analyzed using a univariate and multivariate models. Rate and categorical variables were compared by chi-square test with values of P < 0.2 considered to be potential independent variables, and entered into the logistic regression model. The variables of two-tailed P < 0.05 were included in nal model. Statistical analysis was conducted with the SPSS program version 23.0 (IBM Corp., Armonk, NY).

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The characteristics of the patients were shown in Table 1. A total of 187 patients with limb fractures treated with internal xation had surgical site infection. Microbiology: The microorganism most frequently isolated from infected surgical wounds is S. aureus (26.46%), followed by Acinetobacter baumannii (AB) (12.23%) and Pseudomonas aeruginosa (PA) (10.05%). In our study, the infection rate for lower limb fractures is signi cantly higher than that for upper limb fractures (3.75% vs. 0.42%), so we compare surgical site infections of the humerus, radius, and ulna under one category. After adjusting for age, sex and other confounders, the distribution of gram-negative and gram-positive bacteria in different limb fractures is similars (P > 0.2). [ Figure 1] Figure 1: The distribution of microorganisms in limb fractures. We de ned microorganism with frequencies less than 6 times as rare microorganisms.
In orthopaedic common antibiotics, S. aureus is sensitive to Levo oxacin and Moxi oxacin. Moxi oxacin has a good effect on S. epidermis and Streptococcus hemolyticus (S. hemolyticus). AB has poor sensitivity to most antibiotics and Cefoperazone / Sulbactam is the most effective antibiotic. Most antibiotics are effective against Pseudomonas aeruginosa. Klebsiella pneumoniae (KP) is the most sensitive to Cefotaxime. In addition to Ceftriaxone, other antibiotics have a good effect on Escherichia coli (E. coil). [ Table 2] Risk factors: In order to determine limb fracture infection and risk factors affecting the distribution of gram-negative and gram-positive bacteria, we further treated multiple taxonomic variables. Since there were fewer patients with limb fractures under the age of 10 in this hospital, we divided the patients into three groups: 0 < age ≤ 30, 30 < age ≤ 50, and 50 < age. The results showed that advanced age did not increase the risk of SSI, nor did it affect the distribution of gram-negative and gram-positive bacteria (P > 0.05).
Multivariate Logistic regression analysis suggests that wound type and vascular injury at the fracture site can in uence the distribution of gram-negative and gram-positive bacteria. Open fractures (adjusted OR = 2.945 ; 95% CI 1.529-5.674) and vascular injury at the fracture site (adjusted OR = 2.624 ; 95% CI 1.058-6.505) are risk factors for gram-negative bacteria infection. In this study, we also analyze the effect of soft tissue injury on the distribution of gram-negative and gram-positive bacteria in closed fractures and found that soft tissue injury alone do not increase the risk of gram-negative bacteria infection (P > 0.05).
The risk factors associated with SSI by Multivariate Logistic regression analysis are shown in Table 3  Discussion Consistent with previous studies, S. aureus is the greatest threat to orthopedic SSI. S. aureus is continuously colonized in the anterior nasal in about 20% of the population and intermittently colonized in up to 60%. [7,8] Past studies have found that prophylaxis by temporarily removing s. aureus colonized in the anterior nasal passage before surgery or by giving antibiotics to patients screened for positive s.
aureus colonizations can effectively reduce the risk of SSI. [9,10] Ran Schwarzkopf and his colleagues found that S. aureus colonized the anterior nasal of orthopaedic surgeons at a higher rate than patients who received joint replacement and spinal surgery, revealing a potential risk factor. [11] S. aureus has ability to attach to implants. [12] Osteomyelitis is a serious consequence of S. aureus infection. The classic mechanism of S. aureus causing osteomyelitis includes four steps:(1)abscess formation;(2)bio lms formation;(3)invasion of the osteocyte lacuno-canalicular network (OLCN) of bone;(4) intracellular infection. [13] The formation of bio lms is an important step in staphylococcus aureus infection, which limits access of antibiotics to microorganisms. In our study, the sensitivity of S. aureus to methicillin is only 38.78%, far lower than the results of foreign surveys in the same period. [14,15] The proportion of drug-resistant bacteria is on the rise worldwide, suggesting the importance of developing countries in controlling the growth of microbial resistance. In recent years, there have been improvements in measures to prevent SSI in orthopaedic, such as the use of implants with antimicrobial coatings, but this has also increased the risk of developing drug-resistant bacteria. [16] There have been few studies on the association between AB and PA and orthopedic SSI in the past. In our study, AB and PA are signi cantly more distributed in open fractures than in closed fractures, suggesting an increased risk. AB is a common infection in intensive care units. As an opportunistic pathogen, AB mainly affects people with low immunity. [17] The symptoms it causes are usually milder than those of S. aureus. Compared with other hospitals, the proportion of critically ill patients admitted to this hospital is not signi cantly higher, and we suggest that limb fractures may be a potential risk factor for AB infection. Similar to S. aureus, PA can also form bio lms. Recently, Guoqi Wang and his colleagus found that negative-pressure wound therapy can treat treat infections caused by PA. [18] We nd that the distribution of gram-negative and gram-positive bacteria is similar among different limb fractures, suggesting that we may be able to view limb fractures as a whole in terms of microbial composition. Open fractures and vascular injury at fracture site increase the risk of contamination of the wound, and thus more likely to cause infection with gram-negative bacteria.
The basic physical condition play an important role in the postoperative recovery of patients with limb fracture. Consistent with past studies, diabetes and hypoproteinemia increase the risk of infection after fracture surgery [19,20]. High blood sugar provides a breeding ground for microbes to grow, while low protein can delay healing of surgical incisions. Albumin supplementation through diet is easier to maintain than intravenous infusion. Recent study suggests that preoperative enteral protein powder supplementation in patients with hypoproteinemia who recieve hip replacement reduces SSI rates and readmission rates [21].
The immunity and surgical wound healing ability of the elderly patients are decreased compared with the younger patients. Interestingly, in this study, we do not nd that advanced age increased the risk of SSI. After reviewing the treatment measures in the hospital, we nd that elderly patients tend to receive more care, such as additional use of forced-air warming system for warmth, albumin supplementation to a higher level before surgery, and more frequent dressing changes, which may have played a protective role.
Soft tissue injury, vascular injury and nerve injury at fracture sites are important problems that orthopedic surgeons pay close attention to. Our study shows that open fractures, vascular injury and nerve injury at fracture site all increase the risk of SSI. Nerve injury may make the patient insensitive to painful stimuli and reduce the protection of the surgical site. Patients with lower limb fractures have a higher risk of infection than those with upper limb fractures, which may be associated with longer bed time. Tibio bula and patella have less soft tissue coverage, making the wound more likely to become contaminated during trauma.They are also more likely to develop skin tension after surgery.This may account for their higher risk of infection.
Although we have reviewed a long period of time, the multicentre study is still bene cial.