Epidemiology and Risk Factors for Superficial Surgical Site Infections after Appendectomy for Acute Appendicitis: A Secondary Data Analysis

Abstract

Background:

The identification of risk factors for superficial surgical site infections (SSSIs) associated with appendectomy is paramount in the management of patients with acute appendicitis (AA).

Methods:

This study was a secondary data analysis from a prospective multi-center observational study. It included all consecutive hospitalized patients with AA who underwent appendectomy and were monitored for complications at 30 days after the intervention. A case-control approach was used to evaluate risk factors associated with the occurrence of SSSI.

Results:

Among 2,667 patients, 156 (5.8%) developed an SSSI. The series included 1,449 males (54.3%) and 1,218 females with a median age of 29 years (interquartile range [IQR] 20–45 years). Antimicrobial therapy within the previous 30 days was reported by 170 patients (6.4%), and a C-reactive protein concentration (CRP) >50 mg/L was observed in 609 (22.8%). A total of 960 patients (36.0%) underwent open surgery, 1,699 (63.7%) laparoscopic surgery, and 8 (0.3%) another surgical intervention. In 2,575 patients (95.6%), a pathological appendix was detected during the operation. In 776 patients (29.1%), an intra-operative abdominal drain (IAD) was placed; 125 patients (4.7%) were admitted to the intensive care unit. The median hospital length of stay was 3 days (IQR 2–5 days). The overall mortality rate was 0.11%. Multinomial logistic regression analysis of risk factors demonstrated that statistically significant risk factors independently associated with the occurrence of SSSIs were antimicrobial therapy within the previous 30 days, CRP >50 mg/L, open surgical procedures, presence of IAD, and intra-operative findings of complex appendicitis.

Conclusions:

Knowledge of five easily recognizable variables, assessable at hospital admission or as soon as the surgical intervention is concluded, might identify patients with a greater risk of developing an SSSI.

Acute appendicitis (AA) is the most common surgical disease world-wide [1]. Its incidence is stable in most Western countries, but data from newly industrialized countries suggests that AA is rising rapidly [1]. Traditionally, appendectomy—performed through a laparoscopic or an open surgery approach—has been the treatment of choice, and operative management still represents the backbone of treatment by surgeons [2 –4].

Over the past 50 years, a noteworthy reduction has been observed in the mortality rate attributed to AA, from nearly 26% to less than 1% [5]. However, the overall reported incidence of short- and long-term post-operative complications, including surgical site infections (SSIs), still ranges from 3.0%–28.7% [6]. Such infections represent the most common complication for complicated AA surgery [7,8], with an estimated 10% incidence [9]. The economic burden of SSIs is associated with direct medical costs related to prolonged hospitalization [10 –12], intensive care unit (ICU) stay, re-operation [13], and hospital re-admission [14]. Despite the increasing number of appendectomies performed worldwide, a lack of data related to the global epidemiology of SSIs after appendectomy still exists in both developed and developing countries [15,16].

Previous studies have been conducted in surgical settings to identify risk factors for superficial surgical site infections (SSSIs) after appendectomy. Several investigations provided local data obtained from patients recruited from single hospitals or belonging to single countries [17 –23]. However, it seems important to investigate more extensively new and different risk factors that predict the likelihood of occurrence of SSSIs associated with appendectomy from a worldwide perspective.

The objectives of this study were: (1) To analyze a large-scale multi-center dataset of hospitalized patients admitted to surgical departments with a diagnosis of AA who underwent appendectomy and developed an SSSI within 30 days after the surgery; and (2) to identify specific risk factors for SSSIs, which could help to improve the post-operative management and outcome of patients after appendectomy through the prompt implementation of measures of prevention and quick diagnosis of SSSIs.

Patients and Methods

Study population and design

This was a secondary data analysis from a prospective multi-center observational study: The Prospective Observational Study on acute Appendicitis Worldwide (POSAW) study [2], performed between April 1, 2016, and September 30, 2016. This study included all consecutively hospitalized patients admitted to surgical departments with a clinical diagnosis of AA. The POSAW study was performed in 116 surgical departments from 44 countries and enrolled 4,282 patients. The purpose of the POSAW study was to describe the clinical, diagnostic, treatment, and pathological profile of patients with AA in surgical departments in a worldwide context.

In the present study, a case-control approach was used to evaluate the factors associated with the occurrence of SSSIs in enrolled patients who underwent appendectomy and were monitored for complications at 30 days after the intervention.

Case definition

An SSSI was defined according to the U.S. Centers for Disease Control and Prevention (CDC) criteria as infection within 30 days that involved skin and subcutaneous tissue, with any of the following: Purulent drainage, positive culture of microorganisms from fluid or tissue, or at least one of the following symptoms/signs: Pain or tenderness, localized swelling, redness or heat, and superficial incision deliberately opened by the surgeon and either culture-positive or not cultured [24].

Data collection

On admission to a surgical department, the following data were collected from each patient: Gender, age, previous episodes of suspected AA, presence of co-morbidities (primary or secondary immunodeficiency, severe cardiovascular disease), and antimicrobial therapy within the previous 30 days. Clinical and laboratory findings, namely fever (defined as core temperature >38.0°C), leukocytosis (white blood count [WBC] >12,000/mL), and serum C-reactive protein concentration (CRP), were recorded at admission. The type of surgical treatment was listed as open appendectomy (OA), laparoscopic appendectomy, other open interventions (ileocecal resection or lavage and drainage), other laparoscopic interventions (ileocecal resection or lavage and drainage), and other types of intervention. Moreover, the presence of intra-operative abdominal drainage (IAD) and adequate source control were noted, defining the latter as establishment of the cause of AA and controlling its origin [25]. Intra-operative pathological findings were collected. Using the classification system by Bhangu et al. [26], the macroscopic appearance of the appendix was categorized into three subgroups: (1) Normal, if the appendix presented no visible changes; (2) simple, non-perforated appendicitis (including evidence of inflammation, periappendicitis, or suppurative appendicitis); or (3) complex appendicitis (including gangrenous or perforated appendicitis or pelvic or abdominal abscess). Microbiologic results were collected from cultures performed on intra-operative samples of peritoneal fluid or purulent exudate/discrete abscesses to identify gram-negative, gram-positive, and anaerobic bacteria and fungi. Finally, the duration of antimicrobial therapy, admission to the ICU, hospital length of stay (LOS), re-laparotomy (defined as unplanned re-intervention carried out during the immediate post-operative period after appendectomy, causally related to the first operation and performed during the same hospital stay), and death were registered.

Statistical analysis

Data were analyzed as absolute frequency and percentage in the case of qualitative variables. Quantitative variables were analyzed as medians and interquartile ranges (IQRs). The characteristics of patients with and without a diagnosis of SSSIs were compared using the Wilcoxon's rank-sum test for continuous variables and the χ² test for categorical variables.

To identify risk factors independently associated with the occurrence of SSSIs, a multinomial logistic regression analysis was performed considering only independent variables that were able to be evaluated by the physician immediately after the surgical intervention was concluded. We selected only independent variables that had a p value of <0.05 in the univariable analysis. Then, a backward selection method was applied to select a limited number of variables using a likelihood-ratio test for comparing the nested models (α = 0.05). At each step, we removed from the previous model the variable with the highest p value greater than α, checking the fit of the new model and stopping when all p values were less than α.

It was regarded as statistically significant when the p value was <0.05. All statistical calculations were performed using the Stata 9 software package (StataCorp, College Station, TX).

Results

During the study period, 4,282 patients were recorded in the POSAW Study. A total of 2,667 patients (62.3%) were monitored for complications at 30 days after the intervention, and among them, 156 (5.8%) developed an SSSI, and 1,615 patients (37.7%) were lost to follow-up. Considering World Health Organization (WHO) regions, 1,899 patients (71.2%) were collected in countries belonging to the European region, 451 (16.9%) from the region of the Americas, 126 (4.7%) from the Eastern–Mediterranean region, 102 (3.8%) from the Western Pacific region, 70 (2.6%) from the South-East Asia region, and 19 (0.7%) from the African region.

The patients' characteristics, detected before starting the appendectomy and grouped according to the presence or absence of an SSSI, are reported in Table 1. Patients with previous episodes of AA more frequently reported antimicrobial therapy within the previous 30 days before hospital admission (74/225; 32.9% versus 151/2,442; 6.2%; p < 0.001).

Table 1.

Patient Characteristics According to Presence or Absence of Superficial Surgical Site Infection

Variable	Patients with SSSIs	Patients without SSSIs	All patients	P
Variable	(n = 156)	(n = 2,511)	(n = 2,667)	P
Demographic characteristics
Median age (y) (IQR)	42 (28–57)	24 (20–44)	29 (20–45)	<0.001^a
Male	91 (58.3)	1,358 (54.1)	1,449 (54.3)	0.30
AMT within 30 days before admission	23 (14.7)	147 (5.9)	170 (6.4)	<0.001
Previous episodes of AA	19 (3.8)	206 (8.2)	225 (8.4)	0.08
Co-morbidities
Primary or secondary immunodeficiency	6 (3.8)	36 (1.4)	42 (1.6)	<0.05
Severe cardiovascular disease	13 (8.3)	83 (3.3)	96 (3.6)	<0.05
Findings at admission
Fever (core temperature >38.0° C)	57 (36.5)	565 (22.5)	622 (23.3)	<0.001
Leukocytosis (WBC >12,000/mL)	135 (86.5)	2,013 (80.2)	2,148 (80.8)	0.05
C-reactive protein 10–50 mg/L	44 (28.2)	710 (28.3)	754 (28.3)	0.98
C-reactive protein >50 mg/L	68 (43.6)	541 (21.5)	609 (22.8)	<0.001

Data are expressed as n (%) unless otherwise noted. All p values were calculated using two-sided χ² test unless otherwise noted.

Wilcoxon rank-sum test.

AA = acute appendectomy; AMT = antimicrobial therapy; IQR = interquartile range; WBC = white blood cells.

The patients' management and outcomes are described in Table 2. Patients with an intra-operative pathological finding of complex appendicitis were more likely to receive an IAD than those with a finding of normal appendix or simple appendicitis (55.0% versus 19.8%; p < 0.001). On the contrary, patients who had undergone OA were not more likely to receive an IAD than those who underwent laparoscopic appendectomy (LA) or other types of interventions (29.6% versus 28.8%; p = 0.678). Moreover, patients who developed an SSSI were more likely to be admitted to an ICU (11.5% versus 4.3%; p < 0.001) and had a longer hospital stay (5 days [IQR 3–8 days] versus 3 days [IQR 2–5 days]; p < 0.001) than those ones who did not. Finally, the hospital mortality rate was higher in patients with an SSSI, although it was low in both groups (1/156; 0.6% versus 2/2,511, 0.1%; p = 0.042).

Table 2.

Management and Outcome According to Presence or Absence of Superficial Surgical Site Infection

Variable	Patients with SSSIs	Patients without SSSIs	All patients	P
Variable	(n = 156) (%)	(n = 2,511) (%)	(n = 2,667) (%)	P
Type of surgical interventions
Open surgery	99 (63.5)	861 (34.3)	960 (36.0)	<0.001
Open appendectomy	90 (57.7)	842 (33.5)	932 (34.9)	<0.001
Other open intervention	9 (5.8)	19 (0.8)	28 (1.0)	<0.001
Laparoscopic surgery	57 (36.5)	1,642 (65.4)	1,699 (63.7)	<0.001
Laparoscopic appendectomy	57 (36.5)	1,635 (65.1)	1,692 (63.4)	<0.001
Other laparoscopic intervention	0	7 (0.3)	7 (0.3)	0.509
Other type of intervention	0	8 (0.3)	8 (0.3)	0.480
Intra-operative pathologic findings
Normal appendix	1 (0.6)	91 (3.6)	92 (3.4)	<0.05
Simple non-perforated appendicitis	62 (39.7)	1,724 (68.7)	1,786 (67.0)	<0.001
Complex appendicitis	90 (57.7)	615 (24.5)	705 (26.4)	<0.001
Not reported	3 (1.9)	81 (3.2)	84 (3.1)	NA
Presence of IAD	94 (60.3)	682 (27.2)	776 (29.1)	<0.001
Adequate source control	150 (96.2)	2,304 (91.8)	2,454 (92.0)	<0.05
Conversion from LA to OA	23 (14.7)	98 (3.9)	121 (4.5)	<0.001
Re-laparotomy	8 (5.1)	27 (1.1)	35 (1.3)	<0.001
Positive culture from peritoneal swab	44 (28.2)	119 (4.7)	163 (6.1)	<0.001
Median duration of AMT (d; [IQR])	5 (3–8)	4 (2–7)	5 (2–7)	<0.001^a
Admission to ICU	18 (11.5)	107 (4.3)	125 (4.7)	<0.001
Median hospital LOS (d; [IQR])	5 (3–8)	3 (2–5)	3 (2–5)	<0.001^a
Hospital LOS >3 d	110 (70.5)	1,041 (41.5)	1,151 (43.2)	<0.001

Data are expressed as n (%) unless otherwise noted. All p values were calculated using two-sided χ² test unless otherwise noted.

Wilcoxon rank-sum test.

AMT = antimicrobial therapy; IAD = intra-operative abdominal drainage; IQR = interquartile rank; LOS = length of stay.

A total of 479 intra-operative samples of peritoneal fluid or purulent exudate/discrete abscesses were collected (18.0%), and 163 cultures (34.0%) were positive. In 114 cultures (69.9%), only one microorganism was isolated, whereas in 49 (30.1%), two or more pathogens were identified. The most frequent microorganism isolated from peritoneal fluid was E. coli (89; 54.6%) followed by B. fragilis (61; 37.4%), Enterococcus faecalis (20; 12.3%), Klebsiella pneumoniae (14; 8.6%), Streptococcus spp. (13; 8.0%), Enterococcus faecium (11; 6.7%), Enterobacter spp. (5; 3.1%), Staphylococcus aureus (4; 2.5%), three each of Pseudomonas aeruginosa, K. oxytoca, and Clostridiodes spp. (1.8%); two each of Enterococcus spp., Citrobacter spp., and Candida albicans (1.2%); and one each of Proteus spp. and S. epidermidis (0.6%).

The results of multinomial logistic regression analysis of risk factors independently associated with the occurrence of SSSIs after appendectomy are reported in Table 3. The model was highly significant (p < 0.0001), and the global performance of the test is explained by the area under the receiver operating characteristic curve, which is equal to 0.77.

Table 3.

Results of Multinomial Logistic Regression Analysis of Risk Factors for Superficial Surgical Site Infection after Appendectomy

Variable	Odds ratio	95% Confidence interval	P
AMT within previous 30 d	2.04	1.22–3.40	<0.05
C-reactive protein >50 mg/L	1.50	1.04–2.17	<0.05
Open surgery	2.89	2.04–4.10	<0.001
Presence of IAD	2.55	1.75–3.72	<0.001
Complex appendicitis	2.04	1.60–3.41	<0.001

AMT = antimicrobial therapy; IAD = intraoperative abdominal drainage.

Five risk factors were independently associated with the occurrence of SSSIs: Antimicrobial therapy within the previous 30 days before hospital admission, CRP >50 mg/L, open surgical procedures (appendectomy or other interventions), intra-operative abdominal drainage, and intra-operative findings of complex appendicitis. A total of 89.7% of patients (140/156) with at least one risk factor who were monitored for complications at 30 days after the intervention developed an SSSI, whereas in 66.3% of patients with at least one risk factor (1,666/2,511), no SSSI was diagnosed during the follow-up, with a statistically significant difference observed between the groups (p < 0.001).

Discussion

In this secondary data analysis, we observed that the rate of occurrence of SSSIs after appendectomy was 5.8%, a finding consistent with the rate observed in previously published studies [2,17,18,27,28]. Moreover, using multi-variable logistic regression, five independent variables associated with the occurrence of SSSIs were identified, with a good global performance of the test. These risk factors can be assessable at hospital admission (antimicrobial therapy within the 30 days before hospital admission, CRP >50 mg/L) or as soon as the surgical intervention is concluded (open surgical procedures, presence of IAD, and intra-operative findings of complex appendicitis).

Laboratory measurements such as WBC, neutrophil percentage, and CRP serum concentration are commonly used as diagnostic aids in patients with suspected AA. C-Reactive protein is one of the body's acute-phase inflammatory markers, and CRP monitoring can increase the diagnostic accuracy, supporting the surgeon's clinical diagnosis of AA [29]. Moreover, a higher concentration of CRP has been correlated with a more intense local inflammatory reaction, making the appendectomy more challenging technically and predisposing the intervention to a higher rate of complications [30]. In this study, we observed that a pre-operative laboratory finding of CRP >50 mg/L is an independent risk factor for the occurrence of SSSIs after appendectomy. On the contrary, although WBC is a useful laboratory tool to support the clinician in the diagnosis of AA, no statistically significant correlation was found between leukocytosis (WBC >12,000/mL) and SSSI.

We observed that open appendectomy (OA) or other open interventions were independent risk factors for SSSIs, with a statistically significant association in multi-variable analysis. A systematic review recently published by Jaschinski et al. was conducted to compare the effects of LA and OA with regard to benefits and harm [31]. The authors concluded that except for a higher rate of intra-abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, incision infections, length of hospital stay, and time until return to normal activity. In contrast, LA showed advantages over OA in incision infections and LOS in children [31]. Surgeons may prefer OA or other open interventions instead of LA or other laparoscopic interventions for more challenging cases. It might increase the occurrence of SSSIs in the patients who have undergone the former approach, as we observed in our study.

The presence of IAD was a statistically significant risk factor independently associated with the occurrence of SSSIs. There are insufficient data to determine the role of IAD of incisions before closure to prevent SSIs in high-risk patients [32]. Theoretically IADs are used to prevent the accumulation of intra-peritoneal body fluids, blood, and pus between the skin sutures and underlying fascia. By removing these fluids, a medium for bacterial growth, before they become infected, bacterial contamination of the surgical site can be prevented [33], resulting in a reduction in SSSIs. However, the IAD is itself a foreign body that interferes with healing and increases the risk of SSIs. Moreover, the use of a drain may increase the LOS [34]. Recently, a systematic review and meta-analysis observed that the effect of IAD on the prevention of intra-peritoneal abscess or incision infection after OA is unclear for patients with complicated AA. The authors concluded there is no evidence for any clinical improvement with abdominal drainage in patients undergoing OA for complicated AA [35]. Therefore, the routine use of an abdominal drain after laparoscopic appendectomy is still under debate. In adult patients, IAD after appendectomy for complex appendicitis should be used with caution, given the absence of good evidence from the literature [36]. In our study, no predetermined criterion was established for using IAD; we observed that patients with an intra-operative pathological finding of complex appendicitis were more likely to receive an IAD than those ones with a finding of normal appendix or simple appendicitis (55.0% versus 19.8%; p < 0.001). Finally, we can state that IAD placement after appendectomy is the surgeon's decision and should be based on multiple patient and operative variables, which have to be evaluated case by case. Further investigations are needed to explore and evaluate this finding better.

Higher rates of SSSIs in complex than in simple appendicitis have been reported already [8,37,38]. This correlation also was detected in this study: A statistically significant association was observed between intra-operative pathological findings of complex appendicitis and occurrence of SSSIs in patients after appendectomy. The ability of surgeon to assess pathological findings of the appendix adequately intra-operatively has been investigated, and the overall accuracy rate for the correlation of macroscopic assessment of the appendix and the histopathology findings was reported by several studies, ranging from 82.4%–87.3% [39,40]. Nevertheless, as described by Pham et al. in a retrospective study, the observed diagnostic accuracy rate was 100% when findings of gangrenous appendicitis, perforated appendicitis, or abscess were described. Given these pre-conditions, we can suppose reasonably that surgeons' accuracy in the intra-operative assessment of the appendix in correlation with the histopathologic diagnosis of complex appendicitis is high. Identifying complex appendicitis during the intervention represents an important element for the prompt post-operative management of patients, being the essential time factor.

In our study, patients reporting antimicrobial therapy within the 30 days before hospital admission showed a significantly higher risk of SSSI after appendectomy. This finding—to the best of our knowledge—has not been described before, and we could hypothesize a possible explanation considering the role of the cutaneous microbiome in the process of surgical incision healing. Both in vivo and in vitro studies have supported a general consensus that the microbial composition of skin sites impacts acute healing [41]. An alteration in the microbiome balance is associated with antibiotic treatment, as has been described for the cutaneous microbiome [42]. Antibiotic use prompts changes in microbial composition and function during and after the intervention, causing losses in functional diversity and colonization resistance against invading pathogens, implying a danger of antimicrobial resistance [42]. It thus is reasonable to suppose that an antimicrobial treatment within the previous 30 days could have a role not entirely insignificant in increasing the risk of SSSI after appendectomy. This finding implies that patients' antimicrobial history is of key importance. Previous studies have demonstrated that an antimicrobial drug is associated with an increase in the risk of infection with a micro-organism resistant to it [43 –45]. Moreover, inadequate empiric antimicrobial therapy is associated with a longer hospital stay and with more clinical failures and a higher death rate [45 –47]. Surgeons always should identify previous antimicrobial exposure as an important consideration when assessing the risk of occurrence of SSSIs after appendectomy. Further research is needed to investigate and assess this finding better, particularly focusing on type and duration of and indication for the antimicrobial therapy and its relation to previous episodes of AA.

This study identified five easily recognizable variables, assessable at hospital admission or as soon as the surgical intervention is concluded, that were associated with the occurrence of SSSI after appendectomy. The identification of these risk factors could enable the surgeon to implement optimal post-operative incision management practice promptly, especially in patients considered at high risk. The surgeon should monitor and review the process of acute site healing, performing appropriate cleansing and dressing, in order to prevent or recognize early the occurrence of SSSIs and treat them in a timely fashion and appropriately.

This study has some limitations. Its major limitation is inherent in its nature of secondary analysis of data from an observational study conducted previously; in the retrieved dataset, some variables were not collected, and some were not available for a deeper analysis to address particular research questions (i.e., type, dose, and duration of and indication for the antimicrobial therapy administered within 30 days before hospital admission; lack of peri-operative antimicrobial prophylaxis data; comparison of intra-operative and histopathologic findings; antimicrobial susceptibilities of the microorganisms isolated from the cultures performed on intra-operative samples of peritoneal fluid or purulent exudate/discrete abscesses). Moreover, more than a third of the patients were lost to follow-up, creating a selection bias potentially affecting the recorded outcomes. Finally, this study involved many hospitals worldwide but probably not representative. Patients were not homogeneously distributed across all geographic regions of the world, as the majority were collected from countries belonging to the WHO European region, with limited availability of data from Africa and South East Asia. Thus, our results may not be applicable to low- and middle-income countries.

Conclusion

Prompt identification of patients at high risk of occurrence of SSSI after appendectomy is paramount. Our study showed that knowledge of five easily recognizable variables assessable at hospital admission or as soon as the surgical intervention is concluded might guide identify patients with a greater risk of developing an SSSI in the following days. Therefore, it might help the surgeon to put into action the most effective measures for prevention and prompt diagnosis of SSSIs. We trust that the results provided by this study will be valuable for healthcare providers worldwide. These findings represent a step toward further investigations into risk factors for SSSIs in patients after appendectomy.

Footnotes

Funding Information

No funding was received for this article.

Author Disclosure Statement

No competing financial interests exist.

References

Ferris

, Quan

, Kaplan

, et al. The global incidence of appendicitis: A systematic review of population-based studies. Ann Surg, 2017; 266:237–241.

Sartelli

, Baiocchi

, Di Saverio

, et al. Prospective Observational Study on acute Appendicitis Worldwide (POSAW). World J Emerg Surg, 2018; 13:19.

Ansaloni

, Catena

, Coccolini

, et al. Surgery versus conservative antibiotic treatment in acute appendicitis: A systematic review and meta-analysis of randomized controlled trials. Dig Surg, 2011; 28:210–221.

Sartelli

, Viale

, Catena

, et al. 2013. WSES guidelines for management of intra-abdominal infections. World J Emerg Surg, 2013:8; 3.

Berry

, Malt

. Appendicitis near its centenary. Ann Surg, 1984; 200:567–575.

Gorter

, Eker

, Gorter-Stam

, et al. Diagnosis and management of acute appendicitis: EAES Consensus Development Conference 2015. Surg Endosc, 2016; 30:4668–4690.

Andersen

, Kallehave

, Andersen

. Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. Cochrane Database Syst Rev, 2005; 3:CD001439.

Cueto

, D'Allemagne

, Vázquez-Frias

, et al. Morbidity of laparoscopic surgery for complicated appendicitis: An international study. Surg Endosc, 2006; 20:717–720.

Markides

, Subar

, Riyad

. Laparoscopic versus open appendectomy in adults with complicated appendicitis: Systematic review and meta-analysis. World J Surg, 2010; 34:2026–2040.

10.

Coello

, Charlett

, Wilson

, et al. Adverse impact of surgical site infections in English hospitals. J Hosp Infect, 2005; 60:93–103.

11.

Graf

, Ott

, Vonberg

, et al. Surgical site infections: Economic consequences for the health care system. Langenbeck's Arch Surg, 2011; 396:453.

12.

Alfonso

, Pereperez

, Canoves

, et al. Are we really seeing the total costs of surgical site infections? A Spanish study. Wound Repair Regen, 2007; 15:474–481.

13.

O'Keeffe

, Lawrence

, Bojanic

. Oxford Craniotomy Infections Database: A cost analysis of craniotomy infection. Br J Neurosurg, 2012; 26:265–269.

14.

Atkinson

, Jones

, Ousey

, et al. Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis. J Hosp Infect, 2017; 95:148–153.

15.

Rosenthal

, Richtmann

, Singh

, et al. Surgical site infections, International Nosocomial Infection Control Consortium (INICC) report: Data summary of 30 countries, 2005–2010. Infect Control Hosp Epidemiol, 2013; 34:597–604.

16.

Foster

, Kethman

, Cai

, et al. Surgical site infections after appendectomy performed in low and middle human development-index countries: A systematic review. Surg Infect, 2018; 19:237–244.

17.

Giesen

, van den Boom

, van Rossem

, et al. Retrospective multicenter study on risk factors for surgical site infections after appendectomy for acute appendicitis. Dig Surg, 2017; 34:103–107.

18.

Xiao

, Shi

, Zhang

, et al. Surgical site infection after laparoscopic and open appendectomy: A multicenter large consecutive cohort study. Surg Endosc, 2015; 29:1384–1393.

19.

Noorit

, Siribumrungwong

, Thakkinstian

. Clinical prediction score for superficial surgical site infection after appendectomy in adults with complicated appendicitis. World J Emerg Surg, 2018; 13:23.

20.

Fukuda

. Patient-related risk factors for surgical site infection following eight types of gastrointestinal surgery. J Hosp Infect, 2016; 93:347–354.

21.

Galli

, Banz

, Fenner

, et al. Laparoscopic approach in perforated appendicitis: increased incidence of surgical site infection?. Surg Endosc, 2013; 27:2928–2933.

22.

Ming

, Yan

, Tat

. Risk factors of postoperative infections in adults with complicated appendicitis. Surg Laparosc Endosc Percutan Tech, 2009; 19:244–248.

23.

Kasatpibal

, Nørgaard

, Sørensen

, et al. Risk of surgical site infection and efficacy of antibiotic prophylaxis: A cohort study of appendectomy patients in Thailand. BMC Infect Dis, 2006; 6:111.

24.

Horan

, Gaynes

, Martone

, et al. CDC definitions of nosocomial surgical site infections, 1992: A modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol, 1992; 13:606–608.

25.

Sartelli

. A focus on intra-abdominal infections. World J Emerg Surg, 2010; 5:9.

26.

Bhangu

, Søreide

, Di Saverio

, et al. Acute appendicitis: Modern understanding of pathogenesis, diagnosis, and management. Lancet, 2015; 386:1278–1287.

27.

Garcell

, Arias

, Sandoval

, et al. Incidence and etiology of surgical site infections in appendectomies: A 3-year prospective study. Oman Med J, 2017; 32:31–35.

28.

, Tai

, Wang

, Tsai

. Surgical site infection and timing of prophylactic antibiotics for appendectomy. Surg Infect, 2014; 15:781–785.

29.

Shakhatreh

. The accuracy of C-reactive protein in the diagnosis of acute appendicitis compared with that of clinical diagnosis. Med Arh, 2000; 54:109–110.

30.

Shelton

, Brown

, Young

. Preoperative C-reactive protein predicts the severity and likelihood of complications following appendicectomy. Ann R Coll Surg Engl, 2014; 96:369–372.

31.

Jaschinski

, Mosch

, Eikermann

, et al. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev, 2018; 11:CD001546.

32.

De Simone

, Sartelli

, Coccolini

, et al. Intraoperative surgical site infection control and prevention: A position paper and future addendum to WSES intra-abdominal Infections Guidelines. World J Emerg Surg, 2020; 15:10.

33.

Durai

, Mownah

, Ng

. Use of drains in surgery: A review. J Perioper Prac, 2009; 19:180–186.

34.

Allemann

, Probst

, Demartines

, et al. Prevention of infectious complications after laparoscopic appendectomy for complicated acute appendicitis: The role of routine abdominal drainage. Langenbeck's Arch Surg, 2011; 396:63–68.

35.

, Zhao

, Cheng

, et al. Abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis. Cochrane Database Syst Rev, 2018; 5:CD010168.

36.

Di Saverio

, Birindelli

, Kelly

, et al. WSES Jerusalem Guidelines for Diagnosis and Treatment of Acute Appendicitis. World J Emerg Surg, 2016; 11:34.

37.

Margenthaler

, Longo

, Virgo

, et al. Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults. Ann Surg, 2003; 238:59–66.

38.

Kelly

, Fleming

, Aquina

, et al. Disease severity, not operative approach, drives organ space infection after pediatric appendectomy. Ann Surg, 2014; 260:466–471.

39.

Roberts

, Behravesh

, Dmitrewski

. Macroscopic findings at appendicectomy are unreliable: Implications for laparoscopy and malignant conditions of the appendix. Int J Surg Pathol, 2008; 16:386–390.

40.

Pham

, Devadas

, Howle

. Effect of surgical experience on the macroscopic diagnosis of appendicitis: A retrospective cohort study. Int J Surg, 2015; 16:78–82.

41.

Johnson

, Gómez

, McIntyre

, et al. The cutaneous microbiome and wounds: New molecular targets to promote wound healing. Int J Mol Sci, 2018; 19(9).

42.

Ferrer

, Méndez-García

, Rojo

, et al. Antibiotic use and microbiome function. Biochem Pharmacol, 2017; 134:114–126.

43.

Harbarth

, Garbino

, Pugin

, et al. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med, 2003; 115:529–535.

44.

Falagas

, Kopterides

. Risk factors for the isolation of multi-drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa: A systematic review of the literature. J Hosp Infect, 2006; 64:7–15.

45.

Labricciosa

, Sartelli

, Abbo

, et al. Epidemiology and risk factors for isolation of multi-drug-resistant organisms in patients with complicated intra-abdominal infections. Surg Infect, 2018; 19:264–272.

46.

Krobot

, Yin

, Zhang

, et al. Effect of inappropriate initial empiric antibiotic therapy on outcome of patients with community-acquired intra-abdominal infections requiring surgery. Eur J Clin Microbiol Infect Dis, 2004; 23:682–687.

47.

Paul

, Shani

, Muchtar

, et al. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother, 2010; 54:4851–4863.