Antibiotic Prophylaxis In Surgical Site Infection PreventionLailil Indah Seftiani

Rumah Sakit Umum Daerah Kota Bekasilailil_chaofrogy@yahoo.co.id

Abstact- Surgical site infection (SSI) is one of the most common complications of surgery in both adults and children. The purpose of the present review is to highlight the progress in the understanding of SSIs and the role of antimicrobial prophylaxis (AMP).

Keywords: Surgical site infection, antibiotic prophylaxis

I. INTRODUCTION

Surgical site infections (SSIs) are defined as infections occurring up to 30 days after surgery (or up to one year after surgery in patients receiving implants) and affecting either the incision or deep tissue at the operation site. Despite improvements in prevention, SSIs remain a significant clinical problem as they are associated with substantial mortality and morbidity and impose severe demands on healthcare resources. The incidence of SSIs may be as high as 20%, depending on the surgical procedure, the surveillance criteria used, and the quality of data collection. In many SSIs, the responsible pathogens originate from the patient's endogenous flora. The causative pathogens depend on the type of surgery; the most commonly isolated organisms are Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp. and Escherichia coli. Numerous patient-related and procedure-related factors influence the risk of SSI, and hence prevention requires a 'bundle' approach, with systematic attention to multiple risk factors, in order to reduce the risk of bacterial contamination and improve the patient's defences. The Centers for Disease Control and Prevention guidelines for the prevention of SSIs emphasise the importance of good patient preparation, aseptic practice, and attention to

surgical technique; antimicrobial prophylaxis is also indicated in specific circumstances.1

II. SURGICAL SITE INFECTION

Definition

A wound is defined by the Center for Disease Control (CDC) as an interruption or break in the continuity of the external surface of the body or the surface of an internal organ, caused by surgical or other forms of injury or trauma. Surgical site infection is a type of healthcare-associated infection in which a wound infection occurs after an invasive (surgical) procedure. An SSI is diagnosed by a constellation of clinical findings occurring within 30 days of surgery. A surgical site infection (SSI) is clinically defined as presence of pain at a surgically created wound, which is accompanied by erythema, induration and local tenderness or presence of purulent discharge at wound site.2

Surveillance

In 2010, an estimated 16 million operative procedures were performed in acute care hospitals in the United States. A recent prevalence study found that SSIs were the most common healthcare-associated infection, accounting for 31% of all HAIs among hospitalized patients. NHSN data for 2006-2008 (16,147 SSIs following 849,659 operative procedures) showed an overall SSI rate of 1.9%. SSI is associated with a mortality rate of 3%,and 75% of SSI-associated deaths are directly attributable to the SSI.3

Wound status Wound characteristics which increase the risk of SSI include, presence of foreign bodies, nonviable tissue in wound, tissue ischemia and haematoma formation. All of these characteristics provide a fruitful bacterial growing environment. Other factors known to promote SSIs are a prolonged preoperative hospital

stay (since there is a growing opportunity for the skin to be colonized by pathogens), a long operation time (as it probably increases the extent of both tissue trauma and contamination), and poor surgical techniques (see below). The risk of SSI varies with the type of surgery. Certain types of surgery carry a higher risk of contamination than others and have led to the classification of surgical wounds as clean, clean-contaminated, contaminated, or dirty.4

Table 1. Wound class and Classification of the risk of SSI

III. THE MECHANISMS OF BACTERIAL PATHOGENICITY

SSIs are caused by the deposition and multiplication of microorganisms in the surgical site of a susceptible host. There are a number of ways microorganisms colonize and cause infection, including: a) direct contact – either from another patient, transfer from surgical equipment or the hands of the hospital staff; b) airborne dispersal – surrounding air contaminated with micro-organisms that deposit onto the wound; and c) self-contamination (also known as endogenous infection) – physical migration of the patient‘s own normal flora which are present on the skin, mucous

membranes or gastrointestinal tract to the surgical site. Most surgical infection is due to bacterial and, more rarely, fungal infection.

Two broad qualities of pathogenic bacteria underlie the means by which they cause disease:

1. Invasiveness is the ability to invade tissues. It encompasses mechanisms for colonization (adherence and initial multiplication), production of extracellular substances which facilitate invasion (invasins) and ability to bypass or overcome host defense mechanisms.

2. Toxigenesis is the ability to produce toxins. Bacteria may produce two types of toxins called exotoxins and endotoxins. Exotoxins are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth. Endotoxins are cell-associated substance.  (In a classic sense, the term endotoxin refers to the lipopolysaccharide component of the outer membrane of Gram-negative bacteria).  However, endotoxins may be released from growing bacterial cells and cells that are lysed as a result of effective host defense (e.g. lysozyme) or the activities of certain antibiotics (e.g. penicillins and cephalosporins). Hence, bacterial toxins, both soluble and cell-associated, may be transported by blood and lymph and cause cytotoxic effects at tissue sites remote from the original point of invasion or growth. Some bacterial toxins may also act at the site of colonization and play a role in invasion.

Picure 1. Bacterial structureTypical Structure of a Bacterial Cell (from inside to outside)DNA bacterial genetic material

Ribosomes (protein-making factories), energy-generating systems, digestive system, and everything else are located in the cytoplasm.Cytoplasmic Membrane or Inner Membranea. Consists of phospholipids and other membrane proteinsb. Semi-permeablec. Regulates pH, osmotic pressure and availability of essential nutrientsBacterial Cell Wall or Peptidoglycana. Cross-linked mesh that gives a cell its shape, strength and osmotic stability, a protective suit of armourb. Porous up to 100,000 Da.The outer layer of lipopolysaccharide (LPS) and phospholipid material helps protect bacteria from bacteriophages, pH, enzymes, phagocytosis.• To multiply, the bacteria must be able to synthesize peptidoglycan,proteins and DNA

• The cell wall, the ribosomes and DNA are all potential antibiotic targets5

The commonest organism causing SSI is Staphylococcus aureus. Other common causative organisms include other Gram-negative aerobes, Streptococcus spp. and anaerobes. Overall, 144 of the 618 patients studied developed SSIs, with the most common isolates being S. aureus (37%), E. coli (11%), and Enterococcus spp. (5%).

Picture 2. Scanning electron micrograph of Staphylococcus aureus bacteria.

Depending on the particular strain, there are several kinds of toxins attributed to S. aureus virulence. Exotoxins can include toxic shock syndrome toxin-1 (TSST-1), exfoliatins, and enterotoxins. Others may

include alpha-toxin, beta-toxin, delta-toxin, and bicomponent toxins such as Panton-Valentine leukocidin. Factors including protein A, Staphyloxanthin pigment, clumping factor, coagulase, hyaluronidase, leukocidin, and biofilm production can also affect the virulence (Forbes et al., 2007).

Exotoxin TSST-1 causes toxic shock syndrome by stimulating the release of large amounts of interleukin-1 (IL-1) by human monocytes, interleukin-2 (IL-2), and tumour necrosis factor. Similarly, it induces the expression of IL-2 receptors and the proliferation of human T lymphocytes. It does this by binding to MHC class II molecules and the exotonin is produced by most strains of S. aureus (Scholl et al., 1989). In general, the toxin is not produced by bacteria growing in the blood; rather, it is produced at the local site of an infection, and then enters the bloodstream.

IV. ANTIBIOTICSAntibiotics Work

Picture 3. The bacterial cell

Picture 4. Major target for antibacterial action

Picture 5. Sites of antibacterial action

Antibiotics for prophylaxis of SSIs The goals of antibiotic prophylaxis are to achieve inhibitory antibiotic levels at incision and throughout the procedure in an effort to decrease the likelihood of developing a SSI. Antibiotics can also play an important role in the treatment of SSIs. Animal studies have shown that antibiotic prophylaxis is most effective in preventing post-surgical infections when administered before the start of surgery, and pharmacokinetic data suggest administration as near the time of incision as

possible. Classen et al., in a prospective observational study, monitored the timing of antibiotic prophylaxis in 2847 patients in ―clean or ―clean contaminated surgery. Using a step-wise logistic regression model, they found that preoperative antibiotics within two hours of incision had the lowest rate of infection as compared to antibiotics given after incision or earlier than two hours prior.6

In addition to being given preoperatively, prophylactic antibiotics should not be continued postoperatively. A five-month prospective survey of surgical-site infections (SSI) conducted in the department of general surgery at Kilimanjaro Christian Medical Center, Tanzania by Eriksen et al., showed that 77 (19.4%) of the 397 patients studied developed SSI. Twenty-eight (36.4%) of these infections were apparent only after discharge from hospital. A surprising eighty-seven percent of the patients who developed SSI had received antibiotics, the majority having received the antibiotics for several days. Such a practice is contrary to the current recommendation of a single preoperative dose, and prolonged inappropriate use of broad-spectrum antibiotics may contribute to increased emergence of resistance. 7

The type of surgery (clean, clean/contaminated, contaminated, or dirty) also impacts the role of antibiotic prophylaxis. An understanding of this classification, as well as knowledge of recommendations for specific procedures, is invaluable in making an appropriate choice regarding antibiotic prophylaxis. Antibiotic administration in dirty cases is not considered prophylactic as these cases represent treatment of infection rather than prophylaxis.

Controversy exists regarding the use of antibiotic prophylaxis for clean cases. When antibiotic prophylaxis is given, the agent should target S. aureus, the most common organism causing SSIs in clean cases; cefazolin is a good choice. When bone is incised, the use of prophylactic antibiotics is clearly recommended. A good choice in this situation, or for cardiothoracic or vascular surgery, is cefazolin or cefuroxime (or clindamycin or vancomycin for penicillin allergic). For general surgical clean cases, the decision is less clear. A Cochrane Database of Systematic Reviews examined the use of prophylactic antibiotics prior to hernia surgery, and found that infection rates were lower with use of antibiotics (2.9% versus 3.9%) but concluded that ―antibiotic prophylaxis for elective inguinal hernia repair cannot be universally recommended because of overall low infection rates, a high number needed to treat, and a lack of a large, randomized controlled trial to prove efficacy. For clean-contaminated and contaminated cases, antibiotic prophylaxis is recommended. Colorectal surgery is the most thoroughly studied type of procedure in this category, and as such most recommendations are based on studies involving colorectal surgery. The most commonly encountered organism in clean-contaminated and contaminated SSIs is still S. aureus, though other aerobic as well as anaerobic bacteria are also culprits. As such, prophylaxis should be broader than that used for clean cases. Song et al. reviewed all randomized controlled trials of antibiotic prophylaxis in colorectal surgery. Four of these studies compared antibiotic regimens to no antibiotics and showed a convincing benefit of prophylactic antibiotics (odds ratio 0.24, 95% confidence interval 0.13 to 0.43). Further analysis revealed that the most efficacious regimens include coverage against both aerobic and anaerobic organisms (such as a 2nd or 3rd generation cephalosporin, or gentamicin in combination with metronidazole), and cited certain regimens inadequate (metronidazole alone, doxycycline alone, piperacillin alone). Though data from Africa is limited, differences in efficacy between various 2nd and 3rd generation cephalosporins appear negligible, and choice prophylaxis with a single-agent 2nd or 3rd generation cephalosporin can probably be dictated by availability or cost. For penicillin-allergic patients, clindamycin combined with gentamicin, aztreonam, or ciprofloxacin, or metronidazole combined with gentamicin or ciprofloxacin are adequate choices.8,9

A recent “meta-analysis of meta-analyses” involving 250 clinical trials and 4809 patients has provided an estimation of the relative benefit of systematic prophylactic antibiotics to reduce infection for 23 different types of surgery. The type of antibiotic, timing, dosing, and type of procedure varied widely in this analysis, but the relative risk of developing infection for all types of operations with prophylactic systemic antibiotics versus no prophylactic antibiotics varied from 0.19 to 0.82, suggesting a generalized benefit regardless of the degree of contamination. Taken as a whole, the use of prophylactic systemic antibiotics decreased the incidence of wound infections by about one half. This does not mean that prophylactic antibiotics should be used for every case, in as much as there are significant costs involved with their administration, they can have serious adverse effects and there is a risk of the development of antibiotic resistant pathogens or C. difficele colitis. Because of this, there has been reluctance to use prophylactic antibiotics in clean cases.However, prospective randomized studies have shown a clear benefit in clean elective operations such as hernia and breast procedures (SDC-137-141). Recent reports have also shown significant protection against infections in patients with a cesarean section (SDC-142-143). A review of the use of antimicrobial prophylaxis in colorectal surgery, including 182 trials with 3880 participants and 50 different antibiotics, showed a definite benefit of prophylactic antibiotics compared to a placebo or no treatment (RR = 0.30). In that same study, combined therapy against both aerobic and anerobic organisms and combined oral and intravenous antibiotic prophylaxis compared to intravenous alone had significant benefits (RR, 0.41 and 0.74, respectively).10

General principles in surgical prophylaxis 1.Duration of prophylaxis:The duration of antimicrobial prophylaxis should not routinely exceed 24 hours (1 dose at induction and 2 more doses postoperatively, i.e. 3 doses in total). There is wide consensus that only a single dose of intravenous antimicrobial agent is needed for surgical prophylaxis in the great majority of cases. Published evidence shows that antimicrobial prophylaxis after wound closure is unnecessary and could lead to emergence of resistant bacteria. Most studies comparing single- with multiple-dose prophylaxis have not shown benefit of additional doses. 2.Timing: For many prophylactic antimicrobial agents, the administration of an initial dose should be given within 30 minutes before incision (coinciding with the induction of anesthesia) to achieve an adequate tissue concentration at the time of initial incision. This can be facilitated by having the

anesthesiologist administer the drug in the operating room at induction. 3.Antimicrobial dosing: The dose should be adequate based on the patient’s body weight. An additional dose of antimicrobial agent should be given (intraoperatively) if the operation is still continuing after two half-lives of the initial dose or massive intraoperative blood losses occur. Suggested initial dose and time to re-dose for selected antimicrobial agents used for surgical prophylaxis.11

Table 2. Antimicrobial agent

V. CONCLUSION

A wound is defined by the Center for Disease Control (CDC) as an interruption or break in the continuity of the external surface of the body or the surface of an internal organ, caused by surgical or other forms of injury or trauma. Surgical site infection is a type of healthcare-associated infection in which a wound infection occurs after an invasive (surgical) procedure. Surgical site infections (SSIs) are defined as infections occurring up to 30 days after surgery (or up to one year after surgery in patients receiving implants) and affecting either the incision or deep tissue at the operation site. The causative pathogens depend on the type of surgery; the most commonly isolated organisms are Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp. and Escherichia coli. The Centers for Disease Control and Prevention guidelines for the prevention of SSIs emphasise the importance of good patient preparation, aseptic practice, and attention to surgical technique; antimicrobial prophylaxis is also indicated in specific circumstances. The goals of antibiotic prophylaxis are to achieve inhibitory antibiotic levels at incision and throughout the procedure in an effort to decrease the likelihood of developing a SSI. Antibiotics can also play an important role in the treatment of SSIs.

VI. REFERENCES

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http://simplelink.library.utoronto.ca.myaccess.library.utoronto.ca/url.cfm/57821.

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