Epidemiology of Staphylococcus aureus Surgical Site Infections

Abstract

Background:

Surgical site infections (SSI) due to Staphylococcus aureus are associated with substantial mortality rates and morbidity. Hence, various strategies are being investigated to prevent them. We explore time trends and risk factors associated with S. aureus SSI to identify high risk patients who might benefit the most from these strategies.

Methods:

This is a retrospective cross-sectional study on a prospectively maintained database. We identified organism specific risk factors for S. aureus SSI as a whole, methicillin-sensitive S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA). We also identified procedure-specific risk factors for S. aureus SSI for colectomy, hip, and knee arthroplasty, herniorrhaphy, and cholecystectomy.

Results:

We compared 249 patients with S. aureus SSI with 54,988 uninfected control patients. The rate of S. aureus SSI was steady throughout the study period with MSSA being more common than MRSA. Independent risk factors for S. aureus SSI from multivariable analysis were length of hospitalization prior to surgery [odds ratio (OR) 1.01; 95% confidence interval (CI), 1.00–1.02)], colectomy (OR 2.81; 95% CI, 1.94–4.07), hip or knee arthroplasty (OR 1.52; 95% CI, 1.04–2.21), extended duration of surgery (OR 1.61; 95% CI, 1.10–2.37), NNIS score of two or more (OR 2.04; 95% CI, 1.24–3.36), and re-interventions for non-infectious reasons (OR 1.82; 95% CI, 1.16–2.86). Minimally invasive (OR 0.21; 95% CI, 0.13–0.34) and emergency operations (OR 0.61; 95% CI, 0.41–0.92) were protective against S. aureus SSI.

Conclusions:

Future S.aureus SSI prevention measures should focus on patients with risk profiles identified from this and other similar studies.

Surgical site infections (SSI) are among the most common causes of nosocomial infections. They are associated with substantial morbidity and mortality rates, prolonged hospital stays, and increased healthcare costs [1 –4]. Furthermore, the cost of SSI with a resistant organism is considerably higher [5]. In an analysis of 150 patients with SSI due to MRSA, 231 uninfected-matched control patients and 128 patients with SSI due to MSSA, MRSA SSI led to incremental attributable charges in excess of $60,000 when compared with uninfected control patients and in excess of $20,000 when compared with MSSA SSI [6]. Various risk factors have been identified to explain the occurrence of SSI including surgical techniques, duration of surgery, hospital and operating room environment, pre-operative shaving of hair, diabetes mellitus, obesity, and cigarette smoking [7]. However, it remains unclear whether these general SSI risk factors also apply specifically to S. aureus SSI.

Recently, Kaasch et al. [8] published a multi-center comparative analysis of prospective cohort studies investigating the epidemiology, risk factors, and outcome of S. aureus bacteremia. This study, which included Germany, Spain, the United Kingdom, and the United States, showed substantial differences in risk factors between countries. Another study published by Pan et al. from the MOSAR study team concluded that risk profiles of MRSA carriers varies between surgical wards in Europe [9]. This underscores the need for caution in adapting international studies and stresses the need for local data. Surprisingly, there is a paucity of population-based data on the current epidemiology of SSI caused by S. aureus SSI in Western Europe.

Therefore, we identified an urgent need to better elucidate the incidence, prevalence, and risk factors for S. aureus SSI. To this end, we analyzed data from a network of hospitals in Western and Southern Switzerland that participated in a surveillance program for SSI from 1998 to 2010 [10]. The objective of this study is to describe the epidemiology and identify risk factors for S. aureus SSI from this large cohort.

Patients and Methods

In March 1998, six Swiss public hospitals initiated a surveillance program for SSI based on voluntary participation. By December 2010, the number of participating hospitals had increased to 23. Each participant hospital chose among four digestive surgical procedures (appendectomy, cholecystectomy, herniorrhaphy, colon surgery) and since 2002, two orthopedic procedures (first elective hip and knee arthroplasties). The program was developed according to the principles of the US National Nosocomial Infections Surveillance (NNIS) system, currently National Healthcare Safety Network (NHSN) [11,12]. We conducted a retrospective cross-sectional study on the data extracted from this SSI surveillance program.

Demographic and clinical data were prospectively collected in each hospital during hospital stays by trained infection control nurses and post-discharge by means of standardized phone interviews after 1 y for hip and knee arthroplasties and after 1 mo for other surgical procedures. Any suspected or unclear cases were discussed with infectious disease physicians for confirmation of SSI according to the U.S. Centers for Disease Control and Prevention (CDC) definitions. Cases suspected after discharge motivated the search for more information from physicians in charge of the patient, looking for the presence of SSI according to CDC criteria. Data extracted from the SSI surveillance database included type and incidence of SSI (per 1,000 operations) grouped yearly; patient parameters such as age, gender, and American Society of Anaesthesiology (ASA) physical status classification score; and procedure related parameters such as type of procedure, contamination of the incision, duration of operation more than T hours (T hours is the length of time in hours that represents the 75th percentile of procedures reported), time from admission to operation, emergency operation, and pre-operative antibiotic prophylaxis given <1 h prior to incision. The NNIS score was used to stratify risks. ASA score, a measure of physical health status of patients, was divided into <3 or ≥3 as described before [13]. Although all hospitals were included in the risk factor analysis, only hospitals that participated without interruption to the surveillance program from 1998 until 2010 were included in the trend analysis. Entries with incomplete or incorrect data were excluded from risk factors analysis.

Descriptive analysis was performed to determine the prevalence and trend of S. aureus SSI. A case-control study was carried out to identify risk factors for S. aureus SSI, by comparing patients with S. aureus (MRSA and MSSA) SSI with patients without any SSI. Two subgroup analyses were performed, first to identify risk factors for MRSA and MSSA related SSI, and the second to identify surgery-specific risk factors for S. aureus SSI. For procedure-specific SSI, cases were compared with uninfected control patients who had undergone similar procedures. Patients with mixed S. aureus and non–S. aureus SSI were excluded from the final analysis.

Chi-square or Fisher exact tests were used to compare categorical exposure variables, and either the Student t-test or the non-parametric Mann-Whitney U test was used to compare continuous variables depending on their distributions. Variables with a p < 0.2 on univariate analysis were entered into a logistic regression model. For correlated variables (pairwise correlation coefficient >0.7), only one of the covariates was selected for inclusion into the candidate models on the basis of the strength of association. A two-sided p value <0.05 was considered statistically significant. All statistical analyses were done with STATA 12.1.

Results

Between 1998 and 2010, a total of 23 hospitals contributed data to the surveillance program. Nine of these hospitals which participated without interruption were included in the trend analysis. During the same period 62,781 surgical patients were followed prospectively as part of the surveillance program. We excluded 4,622 patients from the risk factor analysis because they underwent procedures not included in the present analysis or because of incomplete or incorrect data entry. Of those included, 54,988 patients (94.5%) did not develop SSI, 2,922 patients (5.0%) had non–S. aureus SSI and 249 patients (0.4%) had S. aureus SSI. Methicillin-resistant Staphylococcus aureus and MSSA contributed to 19.3% and 80.7%, respectively, of S. aureus SSI (Fig. 1). Herniorrhaphy was the most common type of surgery with 14,586 (25.1%) patients, and colectomy was the least common with 8,464 (14.6%) of patients. Patients with appendectomy, cholecystectomy, and hip or knee arthroplasty were 8,923 (15.4%), 13,044 (22.4), and 13,096 (22.5%), respectively.

FIG. 1.

Enrolment of patients. SSI, surgical site infections.

The overall incidence of S. aureus, MSSA, and MRSA SSI in this cohort was 3.97 per 1,000 operations, 3.20 per 1,000 operations, and 0.76 per 1,000 operations, respectively. The overall trend of S. aureus SSI has been stable between 1998 and 2010 (Fig. 2a). MSSA SSI was more common than MRSA SSI in all years except for 2002 and 2006. Staphylococcus aureus SSI trended downwards between 1998 and 2007, but showed an upward movement between 2007 (1.4 per 1,000 operations) and 2010 (3.9 per 1,000 operations), contributed mainly by MSSA SSI. Between 1998 and 2010, the overall trend of MSSA SSI showed a slight increase (Fig. 2b) whereas MRSA SSI showed a decline (Fig. 2c). The changes in trends were not statistically significant.

FIG. 2.

(a) Incidence of S. aureus surgical site infection between 1998 and 2010 for 9 hospitals in Western and Southern Switzerland. (b) Incidence of methicillin-sensitive S. aureus surgical site infection between 1998 and 2010 in Western and Southern Switzerland. (c) Incidence of methicillin-resistant S. aureus surgical site infection between 1998 and 2010 in Western and Southern Switzerland.

Univariate analysis revealed that compared with uninfected control patients, patients with S. aureus SSI were older, stayed longer in the hospital prior to surgery, and had a poorer physical status as denoted by greater ASA score. Colectomy, hip or knee arthroplasty, duration of surgery, NNIS score of two or more, and re-interventions for non-infectious reasons were more common with S. aureus SSI (Table 1). Independent risk factors for S. aureus SSI from multivariable analysis were length of hospitalization prior to surgery (OR 1.01; 95% CI, 1.00–1.02), colectomy (OR 2.81; 95% CI, 1.94–4.07), hip or knee arthroplasty (OR 1.52; 95% CI, 1.04–2.21), duration of surgery above the predefined T-time (OR 1.61; 95% CI, 1.10–2.37), NNIS score of two or more (OR 2.04; 95% CI, 1.24–3.36), and re-interventions for non-infectious reasons (OR 1.82; 95% CI, 1.16–2.86). However, minimally invasive surgery (OR 0.21; 95% CI, 0.13–0.34) and emergency operations (OR 0.61; 95% CI, 0.41–0.92) were associated with a protective effect against S. aureus SSI (Table 1).

Table 1.

Risk Factors for Staphylococcus aureus Surgical Site Infections

			Univariate analysis		Multivariable analysis
Variables	S. aureus SSI (n = 249) (%)	Uninfected (n = 54,988) (%)	OR (95% CI)	p	OR (95% CI)	p
Gender (male)	143 (57.4)	30,349 (55.1)	0.91 (0.71–1.17)	0.48
Age, median years (IQR)	66 (53–77)	61 (44–73)	1.01 (1.00–1.01	<0.001
Days from admission to operation, mean (days)	4	1.3	1.01 (1.01–1.02)	<0.001	1.01 (1.00–1.02)	<0.001
ASA >2	96 (38.6)	10,800 (19.6)	2.57 (1.99–3.32)	<0.001
More than one intervention at the time of surgery	7 (2.8)	949 (1.7)	1.65 (0.77–3.50)	0.19
Type of surgery
Appendectomy	7 (2.8)	8,302 (15.1)	0.16 (0.08–0.34)	<0.001
Cholecystectomy	27 (10.8)	12,618 (23.0)	0.41 (0.27–0.61)	<0.001
Colectomy	88 (35.3)	6,902 (12.6)	3.81 (2.93–4.94)	<0.001	2.81 (1.94–4.07)	<0.001
Herniorrhaphy	54 (21.7)	14,275 (26.0)	0.79 (0.58–1.07)	0.13
Hip or knee arthroplasty	73 (29.3)	12,892 (23.4)	1.35 (1.03–1.78)	0.03	1.52 (1.04–2.21)	0.03
Site of SSI
Superficial	107 (42.9)	N.A.
Deep	69 (27.7)	N.A.
Organ and/or space	73 (29.3)	N.A.
Emergency operation	34 (13.7)	11,420 (20.8)	0.60 (0.42–0.87)	0.01	0.61 (0.41–0.92)	0.02
Surgery under GA	193 (77.5)	41,907 (76.2)	1.08 (0.80–1.45)	0.63
Minimally invasive surgery	25 (10.0)	19,939 (36.3)	0.20 (0.13–0.30)	<0.001	0.21 (0.13–0.34)	<0.001
Wound contamination class ≥3	54 (21.7)	11,502 (20.9)	1.05 (0.77–1.42)	0.77
Duration of surgery > T hours	63 (25.3)	7,261 (13.2)	2.23 (1.67–2.97)	<0.001	1.61 (1.10–2.37)	0.01
NNIS ≥2	63 (25.3)	5,812 (10.6)	2.87 (2.15–3.82)	<0.001	2.04 (1.24–3.36)	0.01
Re-intervention for non-infectious reasons	18 (7.2)	1,121 (2.0)	3.74 (2.31–6.07)	<0.001	1.82 (1.16–2.86)	0.01
Received antibiotics prophylaxis	246 (98.8)	54,309 (98.8)	1.03 (0.33–3.21)	0.97

Appendectomy and herniorrhaphy were removed from logistic regression because of colinearity

Patients with non-S. aureus SSI were excluded from the analysis; non-significant effect sizes are not shown in the multivariable model

SSI = surgical site infection; ASA = American Society of Anaesthesiology score; GA = general anaesthesia; T = length of time in hours that represents the 75th percentile of procedures reported in the NNIS survey; NNIS = National Nosocomial Infections Surveillance; N.A. = not applicable; CI = confidence interval.

The results of surgery-specific multivariable analyses are shown in Table 2. Independent risk factors for S. aureus SSI among patients undergoing hip or knee arthroplasty were days from admission to operation (OR 1.01; 95% CI, 1.00–1.02) and re-interventions unrelated to infections (OR 6.64; 95% CI, 1.58–27.86) whereas age played a protective role (OR 0.98; 95% CI, 0.96–0.99). For patients undergoing colectomy, days from admission to operation (OR 1.02; 95% CI, 1.01–1.03), ASA score of more than two (OR 1.93; 95% CI, 1.04–3.58), and duration of surgery of more than T hours (OR 1.78; 95% CI, 1.00–3.18) were identified as the independent risk factors. Surgery under general anaesthesia (GA) (OR 1.90; 95% CI, 1.03–3.52) and re-interventions unrelated to infections (OR 5.19; 95% CI, 1.49–18.07) were risk factors for herniorrhaphy related S. aureus SSI. Among patients undergoing cholecystectomy, duration of surgery of more than T hours (OR 3.30; 95% CI, 1.31–8.35) was the only risk factor for S. aureus SSI, whereas receiving antibiotics prophylaxis was protective (OR 0.15; 95% CI, 0.03–0.68). Minimally invasive surgery was protective against S. aureus SSI among patients undergoing colectomy (OR 0.29; 95% CI, 0.13–0.65), herniorrhaphy (OR 0.21; 95% CI, 0.06–0.69), and cholecystectomy (OR 0.15; 95% CI, 0.07–0.35).

Table 2.

Procedure Specific Independent Risk Factors for Staphylococcus aureus Surgical Site Infections

	Hip or knee arthroplasty S. aureus SSI (n = 73) vs uninfected control patients (n = 12,891)		Colectomy S. aureus SSI (n = 88) vs uninfected control patients (n = 6,902)		Herniorrhaphy S. aureus SSI (n = 50) vs uninfected control patients (n = 14,275)		Cholecystectomy S. aureus SSI (n = 20) vs uninfected control patients (n = 12,618)
Variables	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p
Age, median years (IQR)	0.98 (0.96–0.99)	0.02
Days from admission to operation, mean (days)	1.01 (1.00–1.02)	0.05	1.02 (1.01–1.03)	<0.001
ASA score >2			1.93 (1.04–3.58)	0.04
Surgery under GA					1.90 (1.03–3.52)	0.04
Minimally invasive surgery			0.29 (0.13–0.65)	0.003	0.21 (0.06–0.69)	0.01	0.15 (0.07–0.35)	<0.001
Duration of surgery > T hours			1.78 (1.00–3.18)	0.05			3.30 (1.31–8.35)	0.01
Re-intervention for non-infectious reasons	6.64 (1.58–27.86)	0.01			5.19 (1.49–18.07)	0.01
Received antibiotics prophylaxis							0.15 (0.03–0.68)	0.01

Multivariable analysis for appendectomy was not reported because of small number of cases (n = 7).

SSI = surgical site infections; ASA = American Society of Anaesthesiology score; GA = general anaesthesia; T = length of time in hours that represents the 75th percentile of procedures reported in the National Nosocomial Infections Surveillance (NNIS) survey; CI = confidence interval.

On subgroup analysis, independent predictors of MRSA SSI (Table 3) were days from admission to surgery (OR 1.02; 95% CI, 1.01–1.03), ASA score >2 (OR 3.65; 95% CI, 1.66–8.02), surgery under GA (OR 8.36; 95% CI, 1.06–66.10), and colectomy (OR 4.43; 95% CI, 1.62–12.15). Emergency procedures (OR 0.25; 95% CI, 0.09 – 0.69) and minimally invasive surgery (OR 0.16; 95% CI, 0.04–0.54) were protective against MRSA SSI. Independent predictors of MSSA SSI were duration of surgery of more than T hours (OR 1.78; 95% CI, 1.14–2.79), colectomy (OR 1.60; 95% CI, 1.03–2.49) and re-interventions unrelated to infections (OR 1.88; 95% CI, 1.03–3.42). Protective factors against MSSA SSI were appendectomy (OR 0.21; 95% CI, 0.08–0.54) and minimally invasive surgery (OR 0.26; 95% CI, 0.15–0.44).

Table 3.

Independent Risk Factors for Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Surgical Site Infections with Uninfected Control Patients as Comparison Group

	Multivariable analysis of methicillin-resistant S. aureus SSI compared with uninfected control patients		Multivariable analysis of methicillin-sensitive S. aureus SSI compared with uninfected control patients
Parameters	OR (95% CI)	p	OR (95% CI)	p
Days from admission to operation, mean (days)	1.02 (1.01–1.03)	<0.001
ASA >2	3.65 (1.66–8.02)	0.001
Appendectomy			0.21 (0.08–0.54)	0.001
Colectomy	4.43 (1.62–12.15)	0.004	1.60 (1.03–2.49)	0.04
Emergency operation	0.25 (0.09–0.69)	0.01
Surgery under GA	8.36 (1.06–66.10)	0.04
Minimally invasive surgery	0.16 (0.04–0.54)	0.003	0.26 (0.15–0.44)	<0.001
Duration of surgery > T hours			1.78 (1.14–2.79)	0.01
Re-intervention for non-infectious reasons			1.88 (1.03–3.42)	0.04

SSI = surgical site infection; ASA = American Society of Anaesthesiology score; GA = general anaesthesia; T = length of time in hours that represents the 75th percentile of procedures reported in the National Nosocomial Infections Surveillance (NNIS) survey; CI = confidence interval.

Discussion

Analysis of this large prospective cohort showed that in Western and Southern Switzerland the rate of S. aureus SSI remained stable between 1998 and 2010. This was similar to the findings from England [14]. However, whereas in our cohort S. aureus SSI was mainly because of MSSA, in the English cohort it was mainly because of MRSA [15]. In comparison in the United States, S. aureus SSI increased between 1998 and 2003 for all types of operations [16]. A decreasing trend in S. aureus (and MRSA) SSI between 2002 and 2013 was recently reported in Australia [17].

As we explore various preventive strategies to reduce S. aureus SSI [18], it becomes crucial to identify patients at the highest risk of SSI who will benefit the most from these interventions. Because there were only a limited number of studies published on risk factors for S. aureus SSI, and with most of those studies looking at MSSA SSI and MRSA SSI separately, we compared our risk factors for S. aureus SSI with a comprehensive list of either MSSA SSI or MRSA SSI risk factors. Some of the risk factors derived from our study concur with previously published reports. These include longer duration of surgery [19 –21], greater ASA score [21], longer in-hospital stay before surgery [22], re-opening of surgical sites [20] and colectomy [21]. However, emergency operation, which was protective against S. aureus SSI in our study, perhaps by reducing the length of in-hospital stay prior to surgery or by the fact that most clean surgery is performed as elective procedure, was found to be a risk factor for MRSA SSI by Harbarth et al. in a single center study from Switzerland [19].

Interestingly, the overall proportion of S. aureus SSI was highest among patients undergoing colectomy (1.3%) followed by hip or knee arthroplasty (0.6%), herniorrhaphy (0.4%), and cholecystectomy (0.2%). To our knowledge, this is the first study to identify S. aureus SSI risk factors for herniorrhaphy and cholecystectomy. Surgery under general anaesthesia and re-intervention for non-infectious reasons were risk factors for herniorrhaphy related S. aureus SSI, whereas long duration of surgery was the only risk factor for cholecystectomy. Minimally invasive surgery was protective against S. aureus SSI, especially among patients undergoing colectomy, herniorrhaphy, and cholecystectomy. This may be because of smaller incisions, earlier mobilisations, and decreased use of central venous catheters among other reasons [23]. Receipt of antibiotic prophylaxis was protective against S. aureus SSI in cholecystectomy (92.6% compliance for cases vs 98.7% among control patients), but not in other operations. This could be because of the fact that compliance to prescription of appropriate antibiotics prophylaxis for other operations was equally high in both cases and control patients, for example among patients undergoing colectomy 98.9% of cases and 99.1% of control patients received adequate antibiotic prophylaxis.

This study adds to the previously known risk factors for MRSA and MSSA SSI and because risk factors were identified from the same cohort, we were able to compare and contrast these two groups of patients. Risk factors unique to MRSA SSI were days from admission to operation, ASA score of more than two, and surgery under general anaesthesia. These findings suggest that pre-surgical in-hospital acquisition of MRSA might be a crucial initiating step toward infection as evidenced by the fact that emergency operations, which are usually associated with short pre-surgical in-hospital stay, were protective against MRSA SSI, whereas a longer duration from admission to operation was a risk factor. This is in contrast to the finding by Harbarth et al. [19] and Manian et al. [24], who suggested that length of stay after surgery is a more important risk factor. Because length of time from surgery to infection was not considered in our analysis, we are unable to deduce a definitive answer from this study.

The study benefits from the use of a large database of prospectively collected information for analysis. Follow-up of patients prospectively in an outpatient setting by means of phone calls and inclusion of family physicians and infectious disease physicians in the diagnosis of outpatient SSI are clearly advantageous for our study. Nevertheless, the data used for this study were collected for epidemiological surveillance and did not include patient level data on other potential confounders for SSI such as diabetes mellitus, obesity, pre-operative S. aureus carriage, and functional status, the inclusion of which may change the risk factor profile observed. Second, similar to the Australian SSI surveillance study [17], the reason for the SSI trend observed in Switzerland is not clear and requires further studies. Third, we found emergency surgery to be protective against MRSA SSI, which could be artificial because no orthopedic operations performed under emergency conditions were included in the surveillance program. Indeed, because emergency operations were registered in the surveillance only for digestive procedures [10], this finding could change substantially if all pathogens causing SSI were included.

The risk factors identified from our study can be used to identify high risk patients for S. aureus SSI. It provides information that can be used by healthcare workers in counselling patients regarding the risk of S. aureus SSI. Future SSI prevention studies should focus on these high risk group patients who stand to gain maximum benefit.

Footnotes

Acknowledgments

Dr. Marimuthu was supported by Health Manpower Development Plan Singapore (HMDP).

Author Disclosure Statement

Drs. Marimuthu, Eisenring, and Troillet report no conflicts of interest. Dr. Harbarth reports having received funding for investigator-initiated research projects funded by Pfizer and B.Braun; he is also a member of the advisory boards of Destiny Pharma, bioMerieux, Novartis, and DaVolterra.

S. aureus SSI prevention studies by Dr. Harbarth leading to this project idea have received support from the Innovative Medicines Initiative Joint Undertaking under the Combatting Bacterial Resistance in Europe (COMBACTE) grant agreement no. 115523, resources of which are composed of financial contribution from the EU's Seventh Framework Programme (FP7/2007–2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in-kind contribution.

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