million per year).90–93 Among the four healthcare-associated infections (pneumonia, SSI, urinary tract

infection, and bloodstream infection), SSIs are the second most common healthcare-associated infection,

accounting for 17% of all healthcare-associated infections among hospitalized patients. A similar rate

was obtained from the National Healthcare Safety Network (NHSN) hospitals reporting data in 2006–

2008 (15,862 SSI following 830,748 operative procedures, with an overall rate of nearly 2%).94

Definitions

SSIs are defined in three specific categories by the Centers for Disease Control and Prevention (CDC),

including superficial incisional SSI, deep incisional SSI, and organ/space SSI (Fig. 8-4, Table 8-12),

dependent on the depth of the infection at the surgical incision site. In addition, the SSI must occur

within 30 days after the operative procedure if no implant is left in place or within 1 year if implant is

in place and the infection appears to be related to the operative procedure. More specific criteria

regarding these definitions are available in the CDC Guideline for Prevention of Surgical Site

Infection.95

Risk Factors for Surgical Site Infection

SSI risk is strongly associated with wound classification, with low risk for SSI in clean and cleancontaminated wound classes, and high risk for SSI in contaminated and dirty–infected wound classes.

Three independent variables have been shown to be associated with SSI risk, initially developed by the

National Nosocomial Infections Surveillance System (NNIS). The NHSN was established in 2005 to

integrate and supersede three legacy surveillance systems at the CDC: the NNIS system, the Dialysis

Surveillance network (DSN), and the National Surveillance System for Healthcare Workers (NaSH).

Similar to the NNIS system, NHSN facilities voluntarily report their healthcare-associated infection

surveillance data for aggregation into a single national database.

The NHSN SSI Risk Index includes an ASA score greater than 2, classification of wound as

contaminated or dirty, and prolonged duration of operation.96,97 Although the risk of infection increases

within the wound classification, it has been shown to be also dependent within each wound class on the

NNIS classification.

Table 8-12 CDC/NHSN Classification of Surgical Site Infections (SSIs)

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Figure 8-4. Surgical site infection (SSI) definitions by CDC.

Cross-section of the abdominal depicted.

Superficial incisional SSI involves only the skin and subcutaneous tissue layer of the incision

Deep incisional SSI involves deep soft tissues (e.g., fascia and muscle layers) of the incision

Organ/space SSI involves any part of the body, excluding the skin incision, fascia or muscle layers, that is opened or manipulated

during the operative procedure (e.g., intra-abdominal abscess or thoracic empyema)

Basic SSI Risk Index

The index used in NHSN assigns surgical patients into categories based on the presence of three major

risk factors:

1. Operation lasting more than the duration cut point hours, where the duration cut point is the

approximate 75th percentile of the duration of surgery in minutes for the operative procedure.

2. Contaminated (class 3) or dirty/infected (class 4) wound class.

3. ASA classification of 3, 4, or 5.

The patient’s SSI risk category is simply the number of these factors present at the time of the

operation.

The laparoscopic surgical approach is associated with decreased SSI incidence, and a modified risk

index (category 1 when procedure was performed with a laparoscope) has been created to address this

approach.

Additional patient-specific risk factors for SSI have also been identified that are not included in this

risk index, including the presence of anemia, blood transfusion intraoperatively, and colonization with

resistant pathogens.97,98 This SSI Risk Index warrants reevaluation for the future, particularly with

regard to resistant pathogens and other patient-specific risk factors that are not modifiable prior to

surgical intervention. It is of paramount importance to include an SSI risk assessment in all future

clinical trials where SSI is a primary outcome measure.

Surgical Site Infection Prevention

Preventive measures for SSI include antimicrobial prophylaxis, sterilization methods, proper ventilation

of operating rooms, use of barriers, no shaving, clipping if hair removal is required, proper surgical skin

preparation and surgical techniques, maintenance of normothermia, glycemic control, and the provision

of supplemental oxygen.93 The National Surgical Infection Prevention (SIP) project was initiated as the

first component of the Surgical Care Improvement Project (SCIP). Initiated in 2003, the SCIP

partnership sought to substantially reduce surgical mortality and morbidity through collaborative

efforts.

Despite evidence of effectiveness of preoperative antimicrobials for SSI prevention and the

publication of guidelines for antimicrobial prophylaxis, it was recognized that use was often suboptimal.

As part of the SIP initiative, three SIP performance measures were developed:

SIP-1: Antibiotic timing: Proportion of patients in whom IV antimicrobial prophylaxis is initiated

within 1 hour before incision

SIP-2: Antibiotic selection: Proportion of patients are given prophylactic antimicrobials consistent with

published guidelines

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SIP-3: Antibiotic discontinuation within 24 hours: Proportion of patients whose antimicrobial

prophylaxis is discontinued within 24 hours after surgery

Numerous studies document that antimicrobial prophylaxis for SSI is most effective when provided 30

to 60 minutes prior to the initial surgical incision, allowing adequate blood and tissue concentrations at

the time of skin incision. Risk of SSI increases when antimicrobial prophylaxis is given too early (more

than 2 hours prior to skin incision) or too late (after skin incision). In a recent study of 4,472 patients,

SSI risk increased incrementally as the interval of time between antibiotic infusion and the surgical

incision increased. These data from a large multicenter collaborative study confirmed lower SSI risk

when surgical antimicrobial prophylaxis with cephalosporins and other antibiotics with short infusion

times were given within 30 minutes prior to surgical incision.99

In addition, the correct antimicrobial must be administered to cover the potential causative

pathogens, dependent on the surgical procedure performed. The SCIP pocket card (Table 8-13) provides

a list of the recommended preoperative antimicrobials for specific surgical procedures. The recent

publication of the “Clinical practice guidelines for antimicrobial prophylaxis in surgery” by the

American Society of Health-System Pharmacists, Infectious Diseases Society of America, Surgical

Infection Society, and Society for Healthcare Epidemiology of America provide evidence-based national

recommendations.100

The first report of the National SIP Project baseline results from a systematic random sample of

34,133 medicare inpatients undergoing surgery in US hospitals in 2001 documented that only 55.7% of

patients received a dose of parenteral antimicrobial prophylaxis within 1 hour before surgical incision.

Antimicrobial agents consistent with published guidelines were administered to 92.6% of patients and

antimicrobial prophylaxis was discontinued within 24 hours of surgery end time for only 40.7% of

patients. Interestingly, only 28% of these surgical patients had compliance with all three of these

performance measures.101

Table 8-13 Recommended Preoperative Antimicrobials for Specific Surgical

Procedures

We have truly made remarkable progress in the United States with appropriate perioperative

antimicrobial prophylaxis since that initial published report. Compliance with SIP-1 measure (antibiotics

within 60 minutes prior to incision) increased from 55.7% to 91.6%; compliance with SIP-2 measure

(guideline antibiotics) increased from 92.6% to 95.8%; and compliance with SIP-3 (antibiotics

discontinued) increased from 40.7% to 87.7%.

Additional Strategies for Surgical Site Infection Prevention

Surgical Hand Antisepsis

Surgical hand antisepsis, to destroy bacteria, is routinely carried out before undertaking invasive

procedures. A recent review of 10 trials confirmed that alcohol rubs used in preparation for surgery by

the surgical team are as effective as aqueous scrubbing in SSI prevention. There is no evidence to

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suggest that any particular alcohol rub is better than another. Evidence from four studies suggests that

chlorhexidine gluconate–based aqueous scrubs are more effective than povidone iodine–based aqueous

scrubs in terms of the numbers of bacterial colony–forming units on the hands.102

Chlorhexidine as Skin Surgical Site Preparation

Preoperative skin antisepsis of the surgical site is performed to reduce the risk of SSI by removal of skin

microorganisms. A review of six randomized controlled trials identified significant heterogeneity and

the trial results could not be pooled. There was no evidence of a benefit in four trials associated with

the use of iodophor-impregnated drapes.103 More recent studies have documented that chlorhexidine

provided superior skin decontamination compared to povidone-iodine.104–107 The most recent Cochrane

systematic review found evidence that preoperative skin preparation with 0.5% chlorhexidine in alcohol

was associated with lower SSI rates following clean surgery than alcohol-based povidone-iodine

paint.108

Appropriate Hair Removal

The preparation of the surgical site has traditionally included the routine removal of body hair,

however, some studies have suggested that this is deleterious. A Cochrane systematic review of 11

randomized clinical trials, and 3 trials (n = 3,193) comparing shaving with clipping, found that there

were statistically more SSIs with shaving than clipping. If it is necessary to remove hair, clipping results

in fewer SSIs than shaving using a razor.109

Normothermia Maintenance During Surgery

Perioperative hypothermia is common and adversely affects clinical outcomes. The primary beneficial

effects of warming are mediated through increased blood flow and oxygen tension at the tissue level.

Hypothermia may facilitate SSI in two ways. First, sufficient intraoperative hypothermia triggers

thermoregulatory vasoconstriction. Second, considerable evidence indicates that mild core hypothermia

directly impairs immune function including T-cell–mediated antibody production and nonspecific

oxidative bacterial killing by neutrophils. Randomized controlled trials have documented that

perioperative warming is associated with a significant reduction in SSI and this simple SSI preventive

strategy should be implemented in all surgical patients.110–112

Normoglycemia Maintenance During Surgery

Perioperative hyperglycemia has been associated with increased SSIs and previous recommendations

have been to treat glucose levels above 200 mg/dL. Recent studies have questioned the optimal

glycemic control regimen to prevent SSIs. A recent Cochrane Database systematic review included five

randomized controlled clinical trials with a total of 773 patients randomized. Due to heterogeneity in

patient populations, perioperative period, glycemic target, route of insulin administration, and

definitions of outcome measures, combination of the results of the five trials into a meta-analysis was

not appropriate. The authors concluded that there is insufficient evidence to support strict glycemic

control in the intra- and postoperative period among surgical patients for the prevention of SSIs.113 A

Cochrane review of 12 trials that randomized diabetic patients to intensive or conventional glycemic

control perioperatively concluded that no significant differences were identified in patients with

diabetes mellitus. However, posthoc analysis indicated that intensive glycemic control was associated

with greater incidence of hypoglycemia episodes.114

There are no randomized trials evaluating immediate preoperative glycemic control in any setting or

intra/postoperative glycemic control in non-ICU patients. High-quality evidence for strict glycemic

control in the intra- and/or postoperative period among surgical ICU patients, cardiac and noncardiac,

to reduce SSIs, independent of other potential benefits, is also lacking. Further large, adequately

powered, well-designed randomized trials are necessary to identify the ideal target for perioperative

glycemic control in patients at high risk for SSIs. Future trials should report all nosocomial infections as

well as SSIs. Given the heterogeneity seen in the included trials, it would appear that trials should be

targeted at very specific populations and attempts to draw broader conclusions should not be made. At

present, we should strive at least to maintain blood glucose <200 mg/dL in the perioperative period in

our surgical patients.

Supplemental Oxygen in Perioperative Period

Several randomized controlled trials have been conducted to assess the benefit of perioperative

supplemental oxygen in SSI reduction, yet meta-analyses have arrived at different conclusions.115–117 On

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careful review, a number of problems with the conduct of these trials are noted: (1) SSI definition was

not consistent with CDC definitions; (2) the interval for assessment of SSI was variable, ranging from 15

to 30 days; (3) SSI was captured retrospectively in some studies and was not always a primary outcome

measure; (4) no assessment of the patient’s individual risk factors for SSI was performed; (5) no control

of perioperative antibiotic prophylaxis timing or selection was performed; and (6) there was variable

provision of high FiO2 supplemental oxygen in each of the studies.118

The first institutional priority should be to universally implement all the evidence-based practices that

reduce SSIs. The “SSI Bundle” from the Institute for Healthcare Improvement includes (1) appropriate

use of antibiotics, (2) appropriate hair removal, (3) perioperative glucose control, and (4) perioperative

normothermia.119 The additional provision of increased inspired oxygen concentrations should be

considered as an additional quality improvement measure, particularly in institutions with high SSI

rates. A collaborative of 44 hospitals implemented the SSI preventive strategies discussed above and

documented a significant reduction in the SSI rate, from 2.3% to 1.7%, representing a 27% reduction

from the first to the last 3 months of the 1-year project.120 Finally, prospective SSI surveillance,

including postdischarge surveillance, should be instituted to obtain accurate information regarding

institutional SSI rates.121

Surgical Site Infection and Colorectal Surgery

Surgical care bundles have been documented to be effective in reducing SSIs in patients undergoing

colorectal surgery and therefore should be implemented.122 Surgeons have held a long-standing belief

that mechanical bowel preparation is an efficient strategy to reduce SSI and anastomotic leak rates

following elective colorectal surgery. Recent systematic reviews have found that there is no statistically

significant evidence that patients benefit from mechanical bowel preparation either in SSI or

anastomotic leak rates.123 In contrast, the use of nonabsorbable enteral antimicrobials covering aerobic

and anaerobic colonic bacteria, in addition to IV preoperative antibiotics, is associated with a significant

reduction in SSI by at least 75%.124–126

Treatment of Surgical Site Infection

Once superficial or deep incisional SSI is diagnosed, “pathogen identification” is of paramount

importance. In years past, the surgical incision was opened and dressing changes were initiated with no

culture of the surgical site obtained. In today’s era of multidrug-resistant pathogens, a Gram stain and

culture of the surgical site should always be obtained in order to determine the optimal antimicrobial

therapy that is required for SSI treatment.

SSI treatment includes four strategies for successful treatment: (1) early empiric antimicrobial

therapy; (2) decision-making regarding whether the surgical site should be opened; (3) pathogen

identification; and (4) deescalation of antimicrobial therapy once culture results are available.

For organ/space SSI, “source control” and “pathogen identification” are both high priorities in order

to achieve successful treatment. In the case of intra-abdominal abscess, source control can be provided

by either interventional radiology percutaneous drainage or open surgical drainage of the abscess.

Abscess fluid should be sent for Gram stain and culture, and empiric antimicrobial treatment should be

deescalated once culture results are available.

Current Challenges in Surgical Site Infection

There are a number of growing challenges in SSI, including resistant pathogens, our increasingly elderly

population, more patients with chronic diseases or immunocompromised states undergoing surgery, and

increasing patients undergoing surgery for solid organ transplantation and placement of prosthetic

devices. MRSA was reported to be the most common cause of SSI in vascular surgery patients (n = 772

over a 2-year period) in 2004.127,128 MRSA has emerged as the leading cause of postoperative infection

in vascular surgery patients, and is associated with substantial morbidity, increased hospital length of

stay, and higher incidences of amputation and graft removal.

Comparison of the causative pathogens for SSI in US hospitals documents that S. aureus increased

from 22.5% (1986–2003) to 30% (2006–2007), with MRSA now the leading causative pathogen,

comprising 49.2% of all isolates.128,129 In a study of 8,302 patients readmitted to US hospitals with

culture-confirmed SSI from 2003 to 2007, it was noted that the proportion of infections due to MRSA

significantly increased from 16.1% to 20.6% and was associated with higher mortality rates, longer

length of stay, and higher hospital costs.130 Based on this important finding, some have strongly

advocated for active screening for nasal carriage of MRSA prior to elective surgery with modification of

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antimicrobials for SSI prevention based on those results.131–133 Eradication of MRSA before surgery

appears to lower SSI rates due to MRSA and is recommended.134,135 In contrast, a prospective

interventional cohort study that employed a universal rapid MRSA admission screening strategy among

21,754 surgical patients at a Swiss teaching hospital reported that nosocomial MRSA infection, including

SSI, did not decrease, but relatively low rates of MRSA infection were present at the start of this

study.136

An “MRSA bundle” has been developed including five components:

1. MRSA nasal screening of patients upon admission, transfer, and discharge using PCR;

2. contact isolation of positive patients;

3. standardized hand hygiene;

4. cultural transformation campaign with staff and leadership engagement through positive deviance;

and

5. ongoing monitoring of process and outcome measures.

Implementation of the MRSA bundle was associated with a significant decrease in MRSA transmission

from 5.8 to 3.0 per 1,000 bed-days, significant reduction in MRSA nosocomial infections (2.0 to 1.0 per

1,000 bed-days), and a significant decrease in overall SSIs, with a 65% reduction in orthopedic MRSA

SSIs and a 1% decrease in cardiac MRSA SSIs.137

The advent of CA-MRSA138,139 has also significantly impacted SSI. Recent studies document that CAMRSA is replacing traditional healthcare-associated or nosocomial MRSA strains in SSI among

inpatients.140 A report from a large community hospital in St. Louis, MO, examined the rates of SSI due

to S. aureus in a total of 122,040 surgical procedures in an earlier period (2003–2006) versus later

period (2006–2007). MRSA was identified as the SSI pathogen in 40% of all inpatients in both time

periods. Interestingly, the percentage of clindamycin-susceptible MRSA (distinguishing CA-MRSA) as an

SSI causative pathogen for inpatients rose from 9% in the early period to 19% in the later period. This

increase in the rate of CA-MRSA SSI was observed only among inpatients, not among ambulatory

patients. Similarly, CA-MRSA has emerged as a leading cause of healthcare-associated infections among

patients with prosthetic joint SSIs.141

The use of perioperative intranasal mupirocin for SSI prevention, particularly in patients with MRSA

nasal colonization, remains controversial. Reviews of multiple clinical trials documented that no

reduction in SSI was seen in general surgery or cardiac surgery patients; however, in nongeneral

surgery patients the use of mupirocin was associated with a reduction in SSI.134,135,142

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