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Surgical antibiotic prophylaxis is very complex and critical .Complex because a lot of elements are responsible for its success. Critical because if not applied appropriately it can lead to infection that may lead to sepsis, organ failure and death. Administration of antibiotic prior to surgery to prevent post-surgical site infection is known as surgical antibiotic (antimicrobial) prophylaxis. To fully understand the concept of surgical antibiotic prophylaxis, I have outlined the principles related to surgical site infection, its prevalence, pathophysiology and risk factors to give an overview of the topic.
1.1 Difference between infection and surgical site infection
The attack of body tissues by micro-organisms can cause various types of diseases; such a process is described as infection. Infection can also include secretion of toxin of different types of micro-organism in their host's tissues or even the process by which these microorganisms differentiate and multiply inside their hosts. Infection can be caused by different types of microorganisms , ranging from parasites ,fungi , bacteria to viruses and can be classified in different ways .One of most common ways used to classify infections are infection duration. Those short duration infection or short term infections are called Acute Infection. On the other hand, those with longer duration are called Chronic Infections.
Surgical site infection is a type of health care associated infection in which a wound infections occur after an invasive "surgical "procedure. (Gibbons, et al., 2011)
1.2 Surgical infection history
The surgeons rarely operated till 1860's, as surgical site infection was complicated and so dangerous. Erichsen, from University College Hospital in London coined the phrase 'hospitalism' for what we now call healthcare-associated infection'. Erichsen, the head surgeon at University College Hospital in London produced a 'hard hitting' book that first described the problem in 1874. (Newsom, 2008)
Between 1870 and 1873 - 36% of those having major amputations died (In four major London Hospitals this was 38% .Such statistics were dreadful. Figures collected from 'all the great centers of civilization' (England, France, Germany, America) for amputations in the largest hospitals to be operated by skillful surgeons showed a 30 - 50% death rate after major amputations. In fact it was safer to be operated on at home, than in hospital. (Newsom, 2008)
In 1867, Lister, the famous English surgeon who was first one to use antiseptic substance during surgical operation , placed carbolic acid into open fractures to sterilize the wound and to prevent sepsis and hence the need for amputation. In 1871, Lister began to use carbolic spray in the operating room to reduce contamination. The technique of spraying the air in the operating room with carbolic acid was used only briefly, as it was recognized that germs in the air were not the main problem. Lister perfected the details of the antiseptic method and continued his research. He developed the surgical use of a sterile (germ-free) thread for closing wounds and introduced gauze dressings. Antisepsis became a basic principle for the development of surgery. Amputations became less frequent, as did death from infections. (Medscape, 2012)
World War I (WWI) resulted in new types of wounds from high-velocity bullet and shrapnel injuries coupled with contamination by the mud from the trenches. Such circumstances made surgical site infection more complicated.
2-Pathophysiology of surgical site infection:-
Although huge advances in antiseptic measures, antibiotics and preoperative precautions, surgical site infection still accounts for high morbidity and mortality.
One of the best way to decrease the rate of surgical site infection (SSI) and obtaining the most desirable surgical outcomes is spreading the knowledge and understanding of pathophysiology among involved health care professionals (surgeons, nurses, anesthesia personnel ,operating room staff ,etc..).
There are multiples of interactive pathways that lead to specific responses which at the end fight against the development of the infection. All these were clearly explained by Charles Brunicardi and his colleagues .(Brunicardi , et al.,2005)
2.1 Primary Pathway (Immuno-inflammatory):
Immune system consists of network of cells that fights against invading pathogens. Immune system response can be subdivided into natural immunity (through cells that circulate in blood vessels or lymph ) or specific immunity .Leukocytes (white blood cells ) ,that can be further classified into ( basophils,eosinophils ,neutrophils, macrophages ) constitutes the primary defense line that rapidly migrates to infection site, engulfing (by macrophages) the invading pathogen in a process called phagocytosis .On the other hand ,the natural killer cells (NKL) and cytokines ( Interleukin1,Interleukin 6,tumor necrosis factor alpha) are the components of specific immunity .Those cells can attack the abnormally dividing cells (cancer cells ) or virus without any prior sensitization.
The inflammatory pathway is then activated after the migration of phagocytes to invading pathogen via releasing more chemical messengers (cytokines, NKL) to alert all other dense mechanisms. (Brunicardi , et al.,2005)
2.2 Neuro-Endocrine Pathway:
Once the main continuous barrier is violated through surgical incision (stress factor ) lead to activation of sympathetic nervous system (Neuro pathway ), that lead to release of endogenous neurotransmitters (adrenaline & nor-adrenaline ) which bind to adrenergic receptors (alpha 1) leading to vasoconstriction ,thus limiting blood supply to injury site to prevent the spread of invading pathogen through circulation.
Again such stress factor , lead to activation of hypothalamus-pituitary-adrenal system (HPA).Hypothalamus (part of the brain with highly specialized cells of important functions ) start to secrete corticotropin factor into circulation (CRF).Corticotropin factor stimulates pituitary gland to release adrenocorticotrophic hormone (ACTH), then ACTH send signals to adrenal gland to release glucocorticoid hormone. After series of metabolism glucocorticoid is converted to cortisol that acts to reduce the immune system response and suppress the inflammation (negative feedback inhibition process).
The equilibrium between those two pathways (immune-inflammatory & neuro-endocrine) help the body to main state of homeostasis (stability ) once the invading pathogen violates the normal physiological barriers of the human body. (Brunicardi,et al.,2005)
3- Incidence and prevalence:
Surgical site infection is the second most common type of health care associated infection. (Wenzel ,2007).Surgical site infections (SSIs) are not an extinct entity; they account for 14-16% of the estimated 2 million nosocomial infections affecting hospitalized patients in the United States.(Medscape 2012) Surgical site infections have been shown to compose up to 20% of all of healthcare-associated infections. At least 5% of patients undergoing a surgical procedure develop a surgical site infection. National Institute for Health and Clinical Excellence Guidelines CG 74 (NICE CG74)
Almost 15 million surgical procedures are annually performed in United States, approximately 300,000 to 500,000 SSI occur each year. (Cruse, 1981)
4-Morbidity and mortality of surgical site infection
Surgical Site infection can incur more suffer to the patient, prolongation of wound healing process, prolonged hospitalization, prolonged antibiotic use and absence from work .(Gagliardi,et al.,2009).Kirkland and his colleagues have quantified such morbidity that can be incurred by surgical site infection. They proved that patients who develop surgical site infection having 60% more probability to stay in intensive care unit than those who don't develop SSI.Also, those patients who develop surgical site infection having 5 times higher chance to be readmitted to the hospital due to SSI complication. Death chance is doubled in patient who develops surgical site infection compared to those who don't. (Kirkland, et al., 1999)
5-Bacteria most commonly involved in SSI:-
One of most common micro-organisms that are involved in SSI is Staphylococcus aureus , hospital reports to CDC shows that 20% of SSI is caused by Staphylococcus aureus.(Table 1) (Wenzel ,2007).On the other hand , almost 37% of SSI that occur in community hospitals are caused by staphylococcus aureus. (Deverick, 2011). Recently, methicillin-resistant staphylococcus aureus (MRSA) became common pathogen in many tertiary care hospitals, academic institutions and community hospitals.
The 10 most common types of pathogens that are responsible for SSIs in hospitals that have been reporting to CDC
Above table represents the results of National Nosocomial Infection Survelliance (NINS) final report that was published on May 1996 in the American Journal of Infection Control.
6-When surgical site infection can occur:-
All types of surgical site infection (SSI) can occur within 30 days post-surgery if no implant was placed, but those surgeries which involve implants or joint replacements can show surgical complication (SSI) within one year and still infection is related to incision. Implant is defined by National Healthcare Surveillance Network (NHSN) as a nonhuman -derived implantable foreign body (ex: prosthetic heart valve , nonhuman vascular graft ,mechanical joint prosthesis ) which is permanently placed for a patient to facilitate or restore the impaired function. Most surgical site infection without implants can develop within 21 days post-surgery. (Sands, et al., 1996)
7-How pathogens overcome host defense mechanisms:-
Most of commonly involved SSI pathogens have intrinsic virulence factors that lead to their ability to cause infection. Many gram-positive orgnanisms,including staphylococcus auerus ,coagulase-negative staphylococcus,and Enterococcus faecalis , possess microbial surface components recognizing adhesive matrix molecules that allow better adhesion to host proteins like collagen ,fibrin, and other extracellular matrix proteins. (Liu, et al., 2004)
In addition to the above, most of these pathogens have the ability to produce very thin biofilm that protect such pathogens from both the host immune system and many antibiotics. (Christensen, et al, 1987)
Exotoxins; are bacterial toxins that are secreted to destroy the tissues of the host , can also lead to increasing the virulence of the invading pathogen such as ,Staphylococci and Streptococci. (Mills, et al.1984).On the other side, gram-negative organisms produce endotoxins that stimulate cytokine production and systemic inflammatory response syndrome in the host. (Morrison, et al1987).Other intrinsic factors that may contribute to virulence are polysaccharide capsule or other surface components that additionally inhibit phagocytosis (Kasper, 1987)
8-Hazard of intraoperative micro-organism contamination:-
Despite numerous factors that contribute to the risk of surgical site infection, the accountability of quantity of pathogens contaminating surgical wound intraoperative remains one of the most established risk factors. The increase in degree of surgical wound contamination, the higher the hazard for infection. If appropriate measures are taken into consideration, such as antimicrobial prophylaxis, wound contamination with with greater than 105 is required to cause surgical site infection. (Houang ,et al.,1991)
Even though, bacterial inoculum that will cause surgical site infection may be much lower when foreign material is placed.(James,et al, 1961) Procedures that requires using surgical sutures decrease required inoculum for staphylococcus auerus by two-thirds (from 106 to 102 organism).(Elek , et al 1957)
9-How surgical site infection can occur:-
The possibility of surgical site infection occurrence depends on many factors. First one is micro-organisms characteristics (e.g.: degree of contamination, virulence of pathogen), another factor can contribute to infection is type of surgery (e.g. : it involves foreign material placement, ), in addition to that , immune status of the patient has great role in SSI development, as those with compromised immune system such as HIV patients or diabetics have higher risk of SSI compared with those who have intact immune status.
Types through which surgical site can get contaminated:-
Patient's flora related (In vivo) contamination :-
The maximum risk of infection can occur during the duration of time between surgical wound incision and closure (Wong, 2004), while surgical wound is open. Almost twenty percent normal bacterial skin flora presents in skin folds, like hair follicles, sweat glands, and sebaceous glands. (Tuazon, 1984)
Advanced antisepsis procedures before and during surgery can help to decrease but never ensure getting rid of the contamination of surgical site by endogenous skin flora of surgical patient. Because of that, gram-positive cocci bacteria from patient's normal flora at or near site of surgery still the major cause of surgical site infection. (Altemeier, et al., 1968)
Sometimes, bacterial contamination of the surgical site by natural flora from remote site of the patient can happen rarely (e.g. : head,),post-surgical infection of the surgical site secondary to remote source of infection is so rare cause of surgical site infection (ex :in rare occasions Streptococcus pneumonia in patients with hospital acquired pneumonia can lead to surgical site infection.) (Edwards, 1976)
External environment related contamination
Surgical site infections can be caused by external contaminating source occasionally.it can happen either because non-sterile operating theatre environment, infected surgical staff, or non-sterile surgical equipment. SSI that develops due to external source doesn't occur frequently, but a lot of exogenous SSI epidemics have been identified. (Berkelman,et al.,1982).
As pre-and perioperative antisepsis measures have been advanced, most of surgical site infection are not developed due to external sources. Rarely some environmental pathogens are implicated in surgical site infection in the operating theatre .Rhodococcus species, was the main cause in an burst of SSI after coronary artery bypass graft surgery due to colonization of an operating theatre staff by her dog.(Richet, et al.,1991). In another well documented event by Lowry and his colleagues, tap water was contaminated with Legionella species, which resulted in prosthetic valves surgical infection. (Lowry ,et al.1991 ).
10-Risk factors that increase possibilities of surgical site infection development:
Many of the patients undergoing surgical procedure suffer from other comorbidities that may result in suppression of their immunity leading to higher risk of surgical infection.
Controlling different chronic medical conditions (ex: diabetes mellitus) patients suffer from prior to surgery will decrease rate of surgical site infection.Actually risk factors can be categorized into 3 classes:
Class 1: Host related risk factors
These risk factors are either obligatory risk factor, that can't be modified such as age of the patient .Age of patient is directly proportional to risk of surgical site infection development. Many clinical trials correlated the age with SSI.One observational trial that was conducted among 142 hospitals defined the age as independent risk factor for surgical site infection .Out of 163624 patients who participated in the trial, 7035 patients were found to have SSI within one month of the surgery. Patients aged 40 and above have statistically significant higher risk of infection than those below age of 40 years (OR 1.24) [Surgical site infection, NICE guidelines .October 2008]
Non-obligatory risk factors that can be controlled are so important in reducing rate of surgical infection. Prolonged hospitalization prior to surgery, increases the chance of the patient to develop nosocomial infection, decreases the immunity, hence increase rate of surgical infection. (Wong, 2004).
Diabetes mellitus is considered to be one of most important factors that should be controlled prior to surgery. High blood glucose prior to surgery serves as an optimum media for growth of bacteria and infection especially at incision site. Chronic diabetic patients may also have suppressed immune system. In National Nosocomial Infections Surveillance System where 84691 patients were involved, they concluded that, diabetic patients having two to three folds increase in possibility of developing SSI (Culver, et al., 1991).
Cigarette smoking has been shown to increase risk of development surgical site infection. Smoking cessation is mandatory prior to surgery and providing adequate cessation advice is important post-surgery. Carbon monoxide and nicotine have vasoconstrictive effect on blood vessels that lead to decrease in tissue oxygenation. A retrospective observational trial involved 3008 patients who underwent cardiac surgery, found that smokers have significant more risk of sternal SSI (OR 1.39) (Ridderstolpe , 2001) .Patient medication before surgery may have role in development of surgical site infection. Medication that alter immunity such as corticosteroids and immunosuppressant drugs are the most implicated.
Class 2: Procedure related risk factors
Complex procedures that last for longer durations (Cardiac surgeries and total hip replacement) have higher chance to develop infections.
Procedures that fail to maintain adequate oxygenation so patient suffers from hypoxia still having higher SSI rates.
Surgeries where patient temperature so they can suffer hypothermia and pH changes, that may be also good media for bacterial growth and development of SSI.
Operation theatre system should organize and accurately define the all criteria that may prevent SSI , such as number of people inside the operation room, antiseptic technique, patient oxygenation and ventilation monitoring,
Class3: Wound care related risk
Wound level of risk was classified by National Academy of science into 4 levels, ranging from clean, clean-contaminated, and contaminated to dirty.
The relation between wound class and SSI was studied in one retrospective analysis for large infection surveillance, they found dirty wound will have higher SSI compare to clean wounds rate per 100 operation was (2.1 vs. 7.1 )for clean and dirty procedures respectively.(Culver, et al.,1991 )
Also techniques used for wound closure after surgery should be sterile .wounds should be covered with sterile dressing for 24-48 hours .Dressing should be changed if the wound is oozing too much.
Post-operative blood transfusion can lead to increase in risk of surgical site infection.
One study demonstrated that transfusion of even single unit of blood can be associated with increased infection. (Hill, et al.,2003).
11-Surgical Site Infection classification:-
Incisional SSI: It is subdivided into either superficial SSI which involve only the skin or subcutaneous tissues of the incision, or deep SSI, that involve deeper layer like fascia or muscles. ( Anderson ,2011)
Organ/space SSI: It includes infections in a tissue deep to fascia that was opened or manipulated during the operation.
12-Antibiotic use history
a-The ancient Egyptians were first to use molds to dress wounds.
b- in 1847 Ignaz Semmelweis used chlorine hand wash.
c- in 1864 Louis Pasteur developed the germ theory of the disease
d- in 1867 Joseph Lister adopted antisepsis principles to the practice of surgery and noticed the presence of molds in urine inhibited bacterial growth.
e- in 1881 Paul Vuillemin used the term antibiosis.
f- in 1890 Rudolf Emmeric and Oscar low discovered "pyocyanase " the first antibiotic , but it didn't work often.
g- in 1928 Alexander Felming discovered penicillinum notatum ability to inhibit staphylococcus auerus.
H-in 1935 Gerhard Domagk discovered "prontasil" the first sulfa drug used.
I-in 1942 Howard Florey and Ernist Chain discovered penicillin.
K-in 1943 the first aminoglycoside antibiotic was released and called streptomycin.
L-in 1955 the Tetracycline was discovered
M-in 1957 Nystatin antifungal was discovered.
N-in 1961 John Burke introduced the concept of antibiotic prophylaxis in surgery when existing skin lesions.
13-Other situations antimicrobials are used in prophylaxis other than surgery
Usually antimicrobial prophylaxis are used in many different places to prevent a lot of infections and ,therefore its use is restricted to the prevention of infections that are rare ,but carry a high mortality or those that are common ,but not fatal (Stone et al.,1979).Antibiotic prophylaxis used in other situations like prevention of recurrent rheumatic fever with continuous penicillin injections, cancer patients who develop neutropenia undergoing bone marrow transplant, and sulfonamide in prevention of bacterial meningitis.
14-Surgical antimicrobial prophylaxis definition
It is the administration of antibiotic (antimicrobial) one to two hours prior to surgical incision to prevent post-operative infection or complication.
15-Aim of surgical antimicrobial prophylaxis:-
Approximately half million surgical site infection occurs each year only in United States each year (Wenzel, 1992). Patients who develop surgical site infection are five times more likely to be readmitted to hospital due to infection or its complication (Kirkland, infection complication than those who didn't develop surgical site infection. In addition to that patients who develop surgical site infection will have higher probability to spend more time in intensive care unit than those who didn't develop surgical site infection.
The consequences of infection also causes a lot of problem for patient due to pain, inflammation, delayed wound healing, prolonged hospitalization, time lost from work and sometimes failure of prosthesis and death.
Economically, care for patients with surgical site infection is much higher than those who didn't develop surgical site infection.in USA, it is estimated that surgical site infection will cost US$ 5155 compared to US$ 1733 in patients who didn't develop surgical site infection. (Perencevich,2003)
So antimicrobial prophylaxis became standards of perioperative care for surgical patients among most of institutions and hospitals worldwide to prevent surgical site infection and its complications, to improve wound healings, to shorten hospitalization, to decrease patient's pain and suffer.
16-Advantages of surgical antimicrobial prophylaxis:-
1-Decrease rate of surgical site infection and its complication.
2-Decrease length of hospitalization
3-Decrease the overall cost of care that will be directed to treat surgical site infection or even the implant of another prosthetic devise due to infection of previous prosthesis.
4-Decrease patient pain and suffer.
5-Avoid other type of infection like pneumonia, endocarditis, sepsis, endocarditis or urine infection in surgical patients especially those with comorbidities or have been on ventilator or tracheostomy. (Arozullah A, 2001)
17-Indications for surgical antimicrobial prophylaxis
A system that classify different types of procedures according to their potential risk for causing infection or even its complication has improved the study of surgical antimicrobial prophylaxis .This classification system divide procedures into :
Generally approved indication for surgical antibiotic prophylaxis are contaminated and clean-contaminated surgery .On the other hand, clean surgery rarely use antimicrobial prophylaxis unless it includes insertion of an artificial device or prosthetic material especially when patients have suppressed immune system, or in patients whom consequence of infection is usually very serious like neurosurgery (ex: craniotomy), open heart surgery, and ophthalmic surgery. (Howar JM, 1964)
18-Principals of surgical antimicrobial prophylaxis
For antibiotic to be given prior to surgery to prevent postoperative infection, a lot of principles should be sought and followed .first principle is to check if the surgery really require prophylaxis and that such practice is evidence based.
Second principle, is to determine exactly the pathogen that will be most likely involved in post-operative infection, this can be done through revising the local hospital surveillance data and antibiotic bio gram.
Third principle, to select the appropriate antibiotic that will target the previously defined pathogen .Never use antibiotics with wide spectrum of activities.
Forth principle, which considered is the most important, is to administer the right dose of antibiotic at right time "60 minutes before incision "
Fifth one is to avoid using surgical antimicrobial prophylaxis to overcome poor surgical technique.
Last principle, to revise and review antibiotic prophylaxis guidelines as both cost and hospital resistances patterns change over time.
18.1 Timing of antimicrobial prophylaxis:
The main goal of antimicrobial prophylaxis is to achieve serum and tissues drug concentrations that exceed minimum inhibitory concentration for the likely pathogen to cause infection during the whole operation. Nine years ago (in January 2003 ) Surgical Infection Prevention Guideline Writers Workgroup (SIPGWW) to review current guidelines of surgical antimicrobial prophylaxis , help to improve them and reach consensus among issues of controversies.
Bratzler and Houck in 2004 published the consensus positions of SIPGWW and it includes that : "infusion of the ¬rst antimicrobial dose should begin within 60 min before surgical incision and that prophylactic antimicrobials should be discontinued within 24 h after the end of surgery".
It is established long time ago ,since 1961 when Burke found that he couldn't recognize experimental incision contaminated staphylococcus auerus from those had not been contaminated with micro-organisms when the antibiotic is administered within 3 hours of bacterial inoculation to experimental incision. (BURKE , 1961 ).
Also Stone et al ,1976 proved that surgical site infection rate is the lowest when antibiotic is administered 1 hour before incision during various type of operations including gastrointestinal, biliary and colon. (Stone , et al .1976 )
A lot of clinical trials have been conducted to indicate importance of these principles to facilitate success of surgeries without postoperative complications. Steinberg and his colleagues conducted randomized prospective trial among 4472 patients who underwent different operations, cardiac, hip/knee ,arthroplasty and hysterectomy cases.
His main objective was to determine optimal time for surgical antimicrobial prophylaxis administration associated with risk of surgical site infection. (Steinberg, et al., 2009)
The main observation of his work, he found that rate of surgical site infection is directly proportional to interval of time between the antibiotic infusion and incision (overall association between timing and infection risk P = 0.04). Table (2) shows the relationship between surgical site infection and timing of antimicrobial administration before incision.
Table 2 the correlation between timing of administration of antibiotic and SSI
Risk of infection
Timing of antibiotic before incision
No administered OR given more than 120 minutes before incision.
61-120 min before incision
31- 60 min before incision
0 - 30 min before incision
1 - 30 min after incision
>31 min after incision
Table 2 Source: (Steinberg, J.P., Annals of Surgery 2009; 250: 10-16)
Source: (Stienberg, J.P.,Annals of Surgery 2009; 250: 10-16)
So he concluded that there is consistent relationship between timing of antimicrobial prophylaxis and surgical site infection risk with a trend of lowest risk of such infection when antimicrobial is injected within 30 minutes prior to incision.
Kasteren and et al, have demonstrated that huge impact of delayed antimicrobial prophylaxis after surgery following total hip arthroplasty.. Among 1922 patients who underwent elective total hip arthroplasty in 11 hospitals that participated in the Dutch intervention project, Surgical Prophylaxis and Surveillance, SSIs (super¬cial and deep) occurred in 50 patients (2.6%). The highest odds ratios for SSI were found in patients who received prophylaxis after incision.
So timing of antimicrobial administration is so critical factor in preventing surgical site infection and such importance facilitated its use as quality indicator for surgeons to prevent surgical site infection. Even though, there is no strict rules in place to help such principle to be monitored closely and document exact timing of administration, as doctors can easily administer antibiotic 5 minutes before incision to avoid any legal responsibilities , but still such close administration may not ensure adequate tissue and serum levels at the time of flora violation .
18.2 Duration of surgical antimicrobial prophylaxis
A lot of research have been conducted in this area to optimize surgical antimicrobial prophylaxis .Longer duration of antibiotic prophylaxis not only associated with very high cost, but it can lead to development of virulent and resistant strains of bacteria. The practice of continuing antibiotic prophylaxis while surgical drains are in-situ is of unproven benefit. Most studies comparing single-dose prophylaxis with multiple-dose prophylaxis have not shown benefit of additional doses. (McDonald,1998)
Most of published guidelines clearly recommends that surgical antimicrobial prophylaxis should be discontinued after wound closure, and many studies that compare single dose prophylaxis versus multiple doses failed to show any benefits with multiple doses (Harbarth, 2000).The agreement of of the National Surgical Infection Prevention Project (NSIPP), representing more than 12 nursing and surgical societies, is that prophylaxis should not extend beyond 24 hours after wound closure. (Bratzler, 2004)
Cardiac surgery are the only surgery that have been proven that 48-72 hours surgical antibiotic prophylaxis is crucial to optimize prophylaxis and prevent post-operative infections. American society of health- system pharmacists (ASHP) advise continuing antimicrobial prophylaxis for cardiac surgeries up to 72 hours after the operation.(ASHP guidelines on antimicrobial prophylaxis,1999).
Tamayo and his colleagues have performed research recently in 2008 comparing the single dose versus multiple doses in patients undergoing elective coronary bypass grafting, valve operations or both. The study was well conducted randomized double blinded and included 838 patients who underwent cardiac surgery in Valladolid university hospital in Spain. The main goal of the study to compare single dose of cefazolin (2 gm.) versus multiple doses of cefazolin ( loading dose which is 2 gm. followed by 1 gm. every 8 hr. ) through detection of surgical site infection during 12 months follow up period. A total of 419 patients received single-dose cefazolin, and another 419 received the 24-hour treatment. Surgical site infection occurred in 35 (8.3%) patients receiving single doses and 15 (3.6%) patients administered the 24-hour treatment (P = .004). Such results were in favor of the recommendation of ASHP that cardiac surgery patients need more than 24 hour surgical antibiotic prophylaxis.
Many other societies still recommend use of surgical antibiotic for maximum of 24 hrs. like American The American Academy of Orthopedic Surgeons has also issued such a statement, explicitly stating that evidence does not support continuing prophylactic antibiotics until all drains or catheters are removed.
18.3 Dose of Antibiotic in surgical antimicrobial prophylaxis
The dose of antibiotic should be enough to allow adequate tissue and blood concentration above the MIC (minimum inhibitory concentration) of the likely pathogen to cause surgical site infection. Dose should be calculated on the basis of body weight, adjusted body weight or body mass index (used for obese patients when their actual body weight is 30% more than ideal body weight).
Usually a single standard therapeutic doses of antibiotic is sufficient for prophylaxis under most circumstances. (SIGN 104, JULY 2008)
Redosing (2nd dose) of antibiotic is recommended in long duration surgeries , re-adminstration is advised one to two times the half-life of the antibiotic with same dose used initially. Only in certain circumstances where there is severe trauma or gross contamination extending prophylaxis from 24-48 hrs is beneficial.( Dellinger ,1991).
18.4 Choice of Antibiotic in surgical antimicrobial prophylaxis
Antibiotic supposed to be used for surgical prophylaxis, should target the most likely pathogen (known from hospital anti-biogram) that will cause post-surgical site infection .Wide spectrum antibiotics shouldn't be used in prophylaxis and better to be reserved for severe infections .(Anon. ,2009).
The choice of antibiotic depends on multiple of factors :-
1-Should match the hospital anti-bio gram (Haley,et al., 1981 ) and current recommendation in literature.
2-Should have the least side effects.
3-Should target suspected pathogen and not all pathogen presents in the flora.
4-if two antibiotics are similar in the above criteria, then choice should favor least expensive.
5-History of patient allergy to certain antibiotic (ex: penicillin or cephalosporin)
Antibiotic prophylaxis is strongly recommended for all clean-contaminated surgeries, and in certain clean surgeries in which surgical site infection and its complication would result in catastrophic outcomes for the patient. (Ex: patients undergoing total joint replacements)(Bratzler, 2005) .In surgical antimicrobial prophylaxis, the chosen antibiotic should cover most likely pathogen to cause infection. Most of surgical site infection occurs due to violation of patient's own flora. Prophylaxis doesn't need to cover all bacterial types existing in patient's flora, as some species are non-pathogenic, or low in numbers or both.(Munckhof , 2005).
In dirty or contaminated surgical procedures ( ex : rupture gall bladder ) the patients don't need any prophylaxis because they are already receiving antibiotic for treatment of existing infection or sepsis. (Anon., 2009)
Cephalosporin are the most common used antibiotics for surgical prophylaxis against surgical site infection. One reason that makes them popular in surgical prophylaxis is their activity against most common skin organisms like staphylococcus and streptococcal species normally found on skin .In some surgeries where anaerobic bacteria can be found, antibiotic combination may be recommended. (Anon,2009).Table 3 presents recommendations of prophylaxis based on type of surgery.
Antibiotic Prophylaxes to Prevent Surgical Site Infections
Staphylococcus aureus, coagulase-negative staphylococci
Cefazolin, cefuroxime sodium (Zinacef), or vancomycin
Enteric gram-negative bacteria, anaerobes, enterococci
Cefoxitin (Mefoxin), cefotetan (Cefotan), ampicillin/sulbactam (Unasyn), or cefazolin plus metronidazole
Gynecologic (vaginal, abdominal, or laparoscopic hysterectomy)
Enteric gram-negative bacteria, group B streptococci, enterococci, anaerobes
Cefoxitin, cefotetan, cefazolin, or ampicillin/sulbactam
S. aureus, coagulase-negative staphylococci
Cefazolin, cefuroxime sodium, or vancomycin
S. aureus, coagulase-negative staphylococci, enteric gram-negative bacilli
Cefazolin or vancomycin
*-Antibiotics are given intravenously within one hour before surgery, except for vancomycin or fluoroquinolones (infusion should start one to two hours before incision).
Source (Antimicrobial prophylaxis for surgery2009.Treatment Guidelines from The Medical Letter, 7(82),pp. 47-52 )
18.4.1 Screening of B-Lactam allergy
Although many patients have penicillin allergy documented in their medical files. The symptoms or circumstances associated with that allergy are rarely doctumented.Alot of studies have showed that incidence of "true " drug allergy is lower than that recorded in patient's medical records. (Hung , 1994 )
Because B-lactam antibiotics are commonly used for prophylaxis, the medical history of patients should be accurate to determine if patient had true allergy (Urticaria ,angioedema,pruritis ,bronchospasm, hypotension or arrhythmia ) or not.
Sometimes some adverse reactions can occur with any type of antibiotics (ex : drug fever, drug-induced hypersensitivity reactions, toxic epidermal necrolysis ) (Robinson ,2002).
In patients who are allergic to cephalosporin, they shouldn't be given penicillin as surgical prophylaxis as there is cross-sensitivity between penicillin and cephalosporin (almost 10%).So providing accurate and full patient's history of allergy is so important in prophylaxis to prevent post-operative infection,
18.4.2 Alternative antimicrobial in case of B-lactams allergy
In surgeries where prophylaxis is directed at gram positive cocci, such as orthopedic surgeries involving total joint replacement, vascular, cardiothoracic and neurosurgical operations with implants (Intra Cranial Pressure device ), an alternative to cephalosporin for patients with documented allergy to cephalosporin are clindamycin or vancomycin.The decision to use either vancomycin or clindamycin depends on hospital anti-biogram, local antimicrobial resistance patterns and local incidence of infections caused by organisms such as Clostridium difficile and Staphylococcus epidermis.
18.4.3 Vancomycin use in surgical antimicrobial prophylaxis
Over the past 20 years, the practice of using antibiotics in surgical prophylaxis has improved significantly, with such antimicrobial agents accounting for about half of all antibiotics prescribed in hospitals. (Bloxham, 1997).
Cefazolin and B-lactam antibiotics have the highest share of those prescriptions targeted for surgical prophylaxis due to their well-established efficacy and safety.(SING Guidelines 104 ,july 2008).
As a result of inappropriate frequent use of antibiotics by many physicians ,the bacterial flora in some hospitalized patients may include multi-resistant bacteria such as methicillin resistant staphylococcus auerus (MRSA ).Evaluation then needs to be made for each patient about whether or not prophylaxis with vancomycin is needed. (Treatment guidelines medical letter, 2009)
Vancomycin may be considered for patients with b-lactam allergy or in institutions with high rates of methicillin resistant Staphylococcus auerus (MRSA) or in cases where there are increase in rate of surgical site infection caused by MRSA.
Frequent and inappropriate use of vancomycin results in emergence of resistant strains such as vancomycin resistant enterococci (VRE ),vancomycin-intermediate staphylococcus auerus (VISA ) and vancomycin resistant staphylococcus auerus (VRSA ) (Munckhof ,2005 ).
The main issue is that, the guidelines and literature don't clearly define the rate of MRSA infection in institutions above which treatment with vancomycin should be necessary (Finkelstein et al, 2002). Furthermore the, studies from institution with high prevalence of MRSA didn't provide adequate evidence that vancomycin is superior to cefazolin in reducing surgical site infection. The final decision to use vancomycin for high risk surgeries should include preference of the surgeons, recommendation of the infectious disease physician, and infection control physicians.
18.4.4 MRSA screening before vancomycin use
Preoperative identification and decolonization of methicillin resistant staphylococcal auerus didn't show to have consistent positive effect in reducing surgical site infection. (Bode, 2010)
Medical letter consultants , didn't solve this issue , as they acknowledge this disagreement .(Treatment guidelines medical letter ,2009).Society of Thoracic Surgeons recommends routine use of topical mupirocin "Bactroban"for all patients planning to undergo cardiothoracic procedures in the absence of documented tests negative for MRSA.The American Academy of Orthopedic Surgeons ,recommends that patients at risk of colonization by methicillin resistant staphylococcus auerus"MRSA" or methicillin sensitive staphylococcus auerus "MSSA"should be tested and treated preoperatively( Evans ,2009)
18.4.5 Patients at risk of MRSA colonization
1-Patients recently discharged from hospital or long term facility.
2-Patients with previous MRSA colonization.
3-Patients with previous MRSA infection.
4-patients on chronic hemodialysis.
5-Intravenous drug users. (Daum , et al ,2007 )
19-Complications of antibiotic use in surgical antibiotic prophylaxis
Using antibiotics in surgical prophylaxis can cause a lot of complications and adverse reactions if not used cautiously and.
19.1 Antimicrobials allergy
Allergy (type 1 anaphylactic reaction ) that is driven by immunoglobuline E, occurs usually within 30 to 60 minutes of administration of the drug (Antibiotic) is considered life threatening. The most common type of antibiotics that are associated with allergy are b-lactam antibiotics (penicillin and cephalosporins).
As both penicillin , and cephalosporin are frequently used in surgical antimicrobial prophylaxis , the possibility of allergic reactions is there. Patient's history of allergy should be carefully obtained through medical record and asking patient's themselves or their relatives before undergoing surgery to minimize such risk. Serious allergic reactions include, skin rashes, urticaria ,angioedema and bronchospasm. The possibility of penicillin-allergic patients to show the same symptoms if cephalosporin is use is less than 1% with first generation cephalosporin, so it is better to avoid using cephalosporin for penicillin allergic patients. By comparing chemical entities of second and third generation cephalosporin to penicillin, they have completely different side chains which minimize risk of cross reactivity. Alternative antibiotics that can be used are azithromycin , gentamicin or in rare cases vancomycin if patients with life threatening allergy to b-lactams.
19.2 Antimicrobials adverse drug reactions
Cefazolin may be associated with increased INR (international normalized ratio )in nutritionally deficient patients and hepatic patients (Lexicomp 2011 ).Prolonged use of most of antibiotics (more than 2 months ) can cause clostridium difficile associated diarrhea and pseudomembranous colitis even it is very rare with b-lactams and most frequent with flouroquinolones.Other antibiotics like vancomycin have more serious adverse effects like nephrotoxicity especially in patients with pre-existing renal impairment.Nuerotoxicity and ototoxicity can be encountered with vancomycin especially in dehydrated and advanced age patients.
19.3 Antimicrobial drug-drug interactions
Antibiotics sometimes can interact with other medications leading to either antagonizing the effect of the other drug or potentiating its effect. Antibiotics also can displace drugs from their protein binding , so more free drug will be available in circulation which can cause toxicity. One example is cefazolin ability to displace antie-eplieptic drug (phenytoin) from its protein binding sites that can lead to higher concentration of free phenytoin in the blood above its maximum therapeutic index which will cause patient's toxicity.(Wolf ,et al,2006).
19.4 Increase cost of the antibiotics
Surgical site infection by far will increase the cost over the government ,hospitals and patients .Antibiotic prophylaxis have clearly demonstrated the direct economic impact on healthcare system , and indirect impact on patients ( ex, labor costs due to absence from work and loss of productivity ), however the magnitude of economic SSI-related burden varies widely across various studies mainly due to difference in country specific healthcare reimbursement systems, in the methodology of the surveillance and the study. So I will not discuss the economic impact of antibiotic by reducing surgical site infection, instead I will shortly comment on the increased cost of antibiotics if used inappropriately. If antibiotics are used for longer duration ( more than recommended by guidelines ) the direct cost will increase.
20. Single dose versus multiple dose prophylaxis
Two years ago, Slobogean and his colleagues from university of British Columbia in Vancouver conducted a trial comparing single-dose versus multiple-dose prophylaxis for the surgical treatment of the closed fracture. The study evaluated the cost of single dose of cefazolin (1 gm) versus four preoperative doses of ceafazolin ( 1 gm) .The single dose prophylaxis had a cost of 2576 USD , while multiple dose prophylaxis had a cost of 2596 USD.The author concluded that single dose prophylaxis is more cost-effective than multiple-dose prophylaxis assuming similar infection rate between two groups.
In other words, giving single dose of antibiotic is as effective as multiple-dose and will reduce the cost on health care systems, government and patients.
CHAPTER 2: AIMS AND OBJECTIVES
To investigate current standard practice of care of our hospital surgeons by checking surgical antibiotic prophylaxis guidelines that are developed by infectious disease hospital committee are correctly implemented to help filling the gap and improving our standard practice of care.
To assess the standard practice of care of surgeons in HMC regarding the choice and duration of antibiotics used for surgery prophylaxis.
To compare the current practice of care with those recommended by the hospital infectious disease expert's guidelines for surgical antibiotic prophylaxis.
To identify any gaps, if present, either in current practice of care and in the recommended guidelines of our hospitals, if applicable.
To provide suitable evidence or recommendations for the surgeons and the ID committee that may help to improve our practice
CHAPTER 3: METHODS
This is observational retrospective study that was conducted in the operating theatre of Hamad General Hospital in Qatar, between April 2011 to June 2011.
Hamad General hospital (HGH) composed of nine operation theatres, the surgeries are performed daily except Friday .Operation theatres are located in ground floor which is very close to other important units like surgical intensive care unit, trauma intensive care unit and emergency department.
The population of the study was selected using purposive sampling (non-probability sampling) that involves intentional selection of the patients of interest from a population to constitute a sample representing the population and exclude those who didn't match the purpose of the study. The population of the study was made up of all patients scheduled for major surgery that require antibiotic prophylaxis "Clean or Clean-contaminated surgeries "during the study period. Contaminated surgeries will be excluded as the antibiotic will be administered as therapeutic intervention .Operation theatre log books were reviewed during that study period ,and patient's health card numbers who underwent surgeries that have well-defined prophylaxis regimen in our hospital guidelines were recorded by me and cross-checked by competent senior theatre nurse.
The data used in this study were collected from operation theatre log books "No computerized data base in operation theatre ", patient's medical records ,patient's medication profile in electronic medical record (eMR) ,patient's microbiological cultures and septic work-up in electronic Medical Records .
The patient's characteristics were also collected including patient identification number (HC) , sex, date of birth, type of surgery , antibiotic allergy, history of chronic illness ,antibiotic type, antibiotic dose , antibiotic route of administration, and duration of antibiotic use. The patient microbiological data were checked to be sure that there is no current infection, and the antibiotics prescribed are only used for surgical prophylaxis.
The data collection sheet was generated from the above mentioned sources. The data was stored electronically in an Excel spread sheet in the researcher's hospital computer with protected passwords. Descriptive statistics were used to summarize all demographic and clinical characteristics of the patients. Associations between two or more than two categorical variables were assessed using Chi-square test. For small cell frequencies appropriate Fisher exact test was applied. Quantitative variables means between the two and more than two groups were analyzed using unpaired t test and one way analysis of variance (ANOVA). Pictorial presentations of key results were made using appropriate statistical graphs. P- value smaller than 0.05 was considered as statistically significant. All Statistical analyses were done using statistical packages SPSS 19.0 ((SPSS Inc. Chicago, IL). Surgical antimicrobial prophylaxis guidelines for the specific surgeries included in our study are attached in appendix 1.
CHAPTER 4: Results
4.1 Patient's characteristics:-
In all , 250 patients charts were reviewed over 3 months period ,149 patients were excluded ,they involved operations that have no clear regimens for antibiotic prophylaxis in our guidelines ,cancer surgeries, infants less than one year of age, contaminated and dirty procedures. The remaining 101 patient's medical records were analyzed and the pharmacy database was reviewed.
Demographic characteristic of the patients are shown in table 4 and diagram 1 while age distribution is show in table 5.
Table 4: Demographics and other clinical variables
No known allergy
Allergy to certain drug
Diagram 1 which represents the gender distribution among study participants.
Table 5: Age distribution among patients
Mean Age (years), N= 101
4.2 Surgery types and surgery class:-
In this study, almost 14 types of surgery were analyzed and evaluated according to our hospital infectious disease surgical antibiotic prophylaxis guidelines. Table 6 represent these types, also it shows surgery class (clean or clean-contaminated) distribution in this study. Diagram 2 shows different surgery frequency in the study. Open reduction internal fixation surgery has been frequently performed during the study 27.7%, while appendectomy came afterward with 13.9%.On the other hand, total hip replacement surgery was performed with lowest rate during study period 1 %.
Table 6 :- Surgery class & surgery type distribution in the study:-
Extra ventricular drainage placement
Mesh repair of inguinal hernia
Clef lip palate
Total hip replacement
Total knee replacement
Trans Ureteral resection of prostate
Aortic valve replacement
ORIF: Open Reduction Internal Fixation; CABG: Coronary Artery Bypass Graft
Diagram 2 : Differenty type of surgery frequency in the study
4.3 Overall use of antibiotics in the study & antibiotic usage frequency :-
Overall use of antibiotic in our study was 89.1 %, most commonly used antibiotic were cefazolin, cefuroxime and ceftriaxone. Least used antibiotics were co-amoxicalve (Amoxicillin+clavulinic acid) , metronidazole,vancomycin and ciprofloxacin. Antibiotic use in the study is represented in table 7.
Table 7: represents antibiotic use in our study and usage frequency for each antibiotic.
4.4 Overall compliance rate to surgical antibiotic prophylaxis guidelines and reasons for non-compliance:-
Overall rate of compliance in this study was 46.5%. Antibiotic duration was longer than recommended in guidelines in 59.3% of procedures, while antibiotic selection for the surgery needed prophylaxis was inappropriate in 31.5 % of the procedures. Prophylaxis wasn't initiated in 9.2 % of surgeries that have clear indications in guidelines for the prophylaxis. All these data are represented in table 8.Rerpresentation of such compliance rate reasons are shown in Diagram 3.
Table 8 : represents overall compliance to our surgical antibiotic prophylaxis guidelines.
Did the practice match protocol
Reason that practice didn't match the protocol :-
Prophylaxis wasn't given
Diagram 3 :- Different elements that were measured in non-compliant surgeries
4.5 Compliance rate (primary outcomes) and its association with surgery class and surgery type:-
4.5.1 Association between surgery class with our hospital guidelines recommendations (Compliance rate):
It was observed that the rate of compliance was significantly higher among clean surgery than clean contaminated group (66% vs. 34%; p=0.03). In this study, 44.4% of clean procedures were shown to be non-compliant to surgical antimicrobial prophylaxis guidelines in our hospitals, while 55.6% of clean-contaminated procedures were shown to be non-compliant.
4.5.2 Association between surgery types with our hospital guidelines recommendations (Compliance rate):
Due to small numbers of surgeries in our study, so I complied different type of surgeries to their main surgical category for example: inguinal hernia, cholecystectomy, appendectomy belongs to general surgery. While craniotomy and extra ventricular drainage placement were compiled under neurosurgery, overall the end result was non-statistical significant difference in compliance rate to our hospital guidelines between all different surgeries ( P= 0.231).Table 9 represents association between both surgery class &surgery type with compliance rate to surgical antibiotic guidelines in our HGH hospital. The relationship between antibiotic use and its compliance with our hospital guidelines has been studied. Overall, 89.1 % of surgeries in our study used antibiotic prophylaxis, those who were adherent with guidelines were only 40.6%, while 48.5% of operations who used antibiotic didn't follow the hospital guidelines. On the other hand,10.9 %of surgeries didn't use antibiotic during our study ,those who were compliant with guidelines represented only 5.9 % ,while those surgeries didn't follow guidelines were 5 %. (the surgeries which supposed to involve antibiotic prophylaxis according to hospital guidelines, but surgeons didn't do so.)
Table 9: Association of surgery class and surgery types with primary outcome
Did the surgery prophylaxis match protocol
Surgery involve artificial device
0 (0 )
13 (24.1 %)
18 (33.3 )
7 (13 )
â€ Chi-Square test
4.6 4.4 Association between different types of antibiotic used during prophylaxis and compliance with our hospital guidelines
In this study, cefzolin has been used most frequently in surgical prophylaxis with usage rate of 44.6 % through whole procedures. In 51.1 % of procedures cefazolin use was in concordance with guidelines recommendations, while in 38.9% its use didn't follow the guidelines of our hospital. While ciprofloxacin and vancomycin are least used antibiotic during this study .Table 10 shows association between different types of antibiotic and compliance with our hospital guidelines.
Table 10:- Association between different antibiotic types and hospital guidelines compliance
Did antibiotic use matched the hospital protocol
CHAPTER 5: Discussion
6.1 Rate of compliance with surgical antibiotic prophylaxis hospital guidelines:-
Surgical antimicrobial prophylaxis use to reduce the rate of surgical site infection is proven to be effective and well established in the literature.(Polk, et al.,2000).In past years , many researchers had detailed how to maximize the prophylaxis , principles of prophylaxis, and guidelines to optimize the patient's care and surgeon's practice.(ASHP , 1991).
Although guidelines are in place many years ago, many studies have shown that inappropriate prophylaxis and poor compliance to guidelines still major issue. (Talon, et al., 2001).It is important to assess and evaluate current practice of surgical antibiotic prophylaxis in order to improve health care outcomes and reduce the gap between both practice and evidence based recommendations. (Wenzel, et al., 1994)
this research didn't evaluate timing of surgical antibiotic prophylaxis; instead it evaluated the compliance rate for both antibiotic selection and antibiotic duration of 102 different procedures that have specific recommendations in our hospital surgical antibiotic prophylaxis guidelines.
In this study, the compliance rate of antibiotic selection with our hospital infectious disease guidelines was 83.2 %, while compliance rate of antibiotic duration with our hospital guidelines was 68.3%.This match with other published papers that tried to evaluate surgical antibiotic prophylaxis among their institutions .one year ago, IMAI-KAMATA and his colleagues from Tokyo medical university school , tried to address the factors responsible for adherence to surgical antibiotic prophylaxis among 2373 patients and found that adherence rate for antibiotic selection was 53-84% while that to antibiotic duration was 38-68% (Imai-kamata,et al.,2011).
In another 3 weeks period study which included 470 patients, was conducted in France and involved 2 periods, separated by period of targeted information, and enforcement of importance of guidelines applications, for both periods before and after targeted information, only 49% of prophylaxis shown to be appropriate. (D'Escrivan ,2005)
Another retrospective study involved 205 patients was conducted among orthopedic trauma patients in Canada to evaluate adherence to antibiotic prophylaxis ,found that less than 32 % of patients received their prophylaxis as recommended. (Lundine,et al.,2010) .
In addition to all of the above, seven years surveillance study conducted in northern France from volunteer surgery wards participating in INCISO surveillance network which involved 8029 patients to assess non-compliance to surgical antibiotic prophylaxis found that only 35 % of surgical antibiotic prophylaxis duration was appropriate. (Astagneau, et al., 2009).
6.2 Antibiotic choice for surgical antimicrobial prophylaxis:
This study showed that cefazolin was the antibiotic with highest usage frequency among 101 procedures which was evaluated. It is used in 44.6 % of all procedure performed, such finding goes in accordance with other published literature that proved cephalosporin antibiotics are the preferred choice in most of surgical procedures. (Bratzler, et al.,2004)
This study showed that ceftriaxone (third generation cephalosporin) was the third most common antibiotic used in surgical prophylaxis with 16.8% of total antibiotic usage. Another trial that was conducted in Germany to measure adherence to surgical antimicrobial prophylaxis guidelines, and involved 29 hospitals found that many of antimicrobials used were broad spectrum involving third generation cephalosporin. (Hohmann, et al., 2011).Broad spectrum antibiotic for surgical prophylaxis is not recommended , as such kind of antibiotic should be used only in severe infection or empirically in acute infection while waiting for the results of cultures. (Tanos, et al., 1994).Wide-spectrum antibiotics should be