Current Guidelines on Antimicrobial Prophylaxis for Surgical Procedures: Minyahil Alebachew Woldu, BPharm Clinical Pharmacy Yr-II Jimma University June 2012 Current Guidelines on Antimicrobial Prophylaxis for Surgical Procedures Presentation Outline: Presentation Outline PowerPoint Presentation: PRESENTATION OBJECTIVES PowerPoint Presentation: Discuss the epidemiology and impact of surgical wound infections on patient outcomes and health care costs. Name and differentiate the four different types of surgical procedures. Recognize the most common risk factors for post-operative wound infections. Identify likely pathogens associated with different surgical operations. PowerPoint Presentation: Compare and contrast antimicrobials used for surgical prophylaxis and identify potential advantages and disadvantages for each antibiotic. Discuss the importance of timing, duration, and redosing in relation to antimicrobial prophylaxis in surgery. Be able to recommend appropriate prophylactic antimicrobial(s) given a surgical operation. Identify non-antimicrobial methods that can reduce the risk of post-operative infection PowerPoint Presentation: Introduction PowerPoint Presentation: Surgical site infections (SSIs) are classiﬁed as either incisional or organ/space (CDC) Incisional SSIs are further divided into superﬁcial incisional SSI (skin or subcutaneous tissue) and deep incisional SSI (deeper soft tissues of the incision). Organ/space SSIs involve any anatomic site other than the incised areas. For example, a patient who develops meningitis after removal of a brain tumor could be classiﬁed as having an organ/space SSI. An infection is considered an SSI if any of the above criteria is met and the infection occurs within 30 days of the operation. If a prosthetic is implanted, the timeline extends out to 1 year . PowerPoint Presentation: Prophylactic antibiotics are widely used in surgical procedures and account for substantial antibiotic use in many hospitals. The purpose of surgical antibiotic prophylaxis is to reduce the prevalence of postoperative wound infection (about 5% of surgical cases overall) at or around the surgical site. By preventing surgical site infections, prophylactic antimicrobial agents have the potential to decrease patient morbidity and hospitalization costs for many surgical procedures that pose significant risk of infection .(e.g., appendectomy) PowerPoint Presentation: However, the benefits of prophylaxis are controversial, prophylaxis is not justified for some surgical procedures (e.g., urologic operations in patients with sterile urine). Consequently, the inappropriate or indiscriminate use of prophylactic antibiotics can increase the risk of : drug toxicity, selection of resistant organisms, and costs. PowerPoint Presentation: EPIDEMIOLOGY AND ETIOLOGY PowerPoint Presentation: In U.S., >40 million inpatient surgical procedures each year; 2-5% complicated by surgical site infection SSIs second most common nosocomial infection (24% of all nosocomial infections) Prolong hospital stay by 7.4 days Cost $400-$2,600 per infection (TOTAL: $130-$845 million/year) Table-1: Factors Affecting the Incidence of Surgical Site Infection: Table-1: Factors Affecting the Incidence of Surgical Site Infection PowerPoint Presentation: Source: Scottish National guideline PowerPoint Presentation: Many experts recommend that antimicrobial prophylaxis should be given for surgical procedures (a) with a high rate of infection, (b) involving the implantation of prosthetic materials, or (c) those in which an infection would have catastrophic consequences. PowerPoint Presentation: PATHOPHYSIOLOGY Prophylaxis versus Treatment: Prophylaxis versus Treatment The distinction between prophylaxis and treatment inﬂuences the choice of antimicrobial and duration of therapy. Appropriate antimicrobial selection , dosing , and duration of therapy differ signiﬁcantly between these two situations. A regimen for antimicrobial prophylaxis ideally involves one agent and lasts less than 24 hours . Treatment regimens can involve multiple antimicrobials with durations lasting weeks to months depending on desired antimicrobial coverage and the surgical site. Types of Surgical Operations: Types of Surgical Operations Surgical operations are classified as clean, clean-contaminated, contaminated, or dirty. Antimicrobial prophylaxis is appropriate for clean, clean-contaminated, and contaminated operations. Dirty operations take place in situations of existing infection and antimicrobials are used for treatment, not prophylaxis : Table-2 : National Research Council Wound Classification (* & **) +National Red Cross Wound Classiﬁcation (* &***) Classification* Criteria* Infection Rate (%)** SSI Risk*** Antibiotic Prophylaxis*** Clean No acute inflammation or entry into GI, respiratory, GU, or biliary tracts; no break in aseptic technique occurs; wounds primarily closed <5 low indicated Clean-contaminated Elective, controlled opening of GI, respiratory, biliary, or GU tracts without significant spillage; clean wounds with major break in sterile technique <10 medium indicated Contaminated Penetrating trauma (<4-hr old); major technique break or major spillage from GI tract; acute, nonpurulent inflammation 15–20 high indicated Dirty Penetrating trauma (>4-hr old); purulence or abscess (active infectious process); preoperative perforation of viscera 30–40 ___ Not indicated; antibiotics used for treatment Source: Koda-Kimble . Applied Therapeutics: Microbiology: Microbiology Choosing the appropriate prophylactic antimicrobial relies on anticipating which organisms will be encountered during the operation. SSIs associated with extra-abdominal operations are the result of skin ﬂora organisms in nearly all cases. These organisms include gram-positive cocci , S. aureus and S.epidermidis being among the most frequently isolated SSI pathogens according to the National Nosocomial Infections Surveillance System ( NNIS ) Thus, for extra-abdominal operations an antimicrobial with strong gram-positive coverage is useful. PowerPoint Presentation: Intra-abdominal operations involve a diverse ﬂora with the potential for polymicrobial SSIs. Escherichia coli make up a large portion of bowel ﬂora Other enteric gram-negative bacteria, as well as anaerobes (especially Bacteroides spp .) Candida albicans is being implicated as the cause of a growing number of SSIs. May be associated with increased use of broad spectrum antibiotic s and rising prevalence of immunocompromised and HIV–infected individuals Despite this fact, antifungal prophylaxis for surgery is not currently recommended. TABLE-3. Major Pathogens in Surgical Wound Infections: TABLE-3. Major Pathogens in Surgical Wound Infections ‘a’ Data reported by the NNIS from 1990 to 1996, adapted from National Academy of the Sciences National Research Council. Table-4:profiles of bacterial isolates identified in postoperative wound infection Gondar University Hospital, November 2010 - February 2011: Table-4:profiles of bacterial isolates identified in postoperative wound infection Gondar University Hospital, November 2010 - February 2011 PowerPoint Presentation: Intra-abdominal operations necessitate broad-spectrum coverage of gram-negative organisms and anaerobes. Anti-anaerobic cephalosporins, cefoxitin and cefotetan , are useful but suffer from limited availability. Fluoroquinolones or aminoglycosides , paired with clindamycin or metronidazole , should provide adequate coverage for intra-abdominal operations. The Hospital Infection Control Practices Advisory Committee allows for the use of vancomycin for surgical prophylaxis when MRSA rates at an institution are “high.” N.B patients who received cefazolin were more likely to develop an SSI due to MRSA . PowerPoint Presentation: Principles of Surgical Antimicrobial Prophylaxis Choosing an Antibiotic: Choosing an Antibiotic Criteria covers expected pathogens (very crucial) should be inexpensive, available in a parenteral formulation, and easy to use. Adverse event potential should be minimal. Choosing an agent with a longer half-life reduces the likely need to redose PowerPoint Presentation: antibiotic ½ life D.F m.o coverage Cost/d Cefazolin 1g 1.8 IV Staphylococci (except MRSA), Streptococci (not Enterococci), E coli, Proteus & Klebsiella * $10 Vancomycin 1g 3 to 9 IV Staphylococcus aureus, Staphylococ- cus epidermidis including MRSA $60 Cefoxitin 1g 0.6 to 1 IV m.o coverage of cefazolin plus bacteroides $30 Cefotetan 3 to 4.6 IV The same as above $30 Aminoglycosides (gantamycin 80mg) 2 IV aerobic Gram-negative bacilli, including pseudomonas $5 Metronidazole 0.5g 8 IV Bacteroides fragilis and against several intestinal protozoa $10 Clindamycin 600mg 2.4 to 3 IV G+ bacteria (staphylococci, pneumococci, Streptococcus pyogenes) and against most anaerobes $10 Ciprofloxacin 400mg 3 to 5 IV Enterobacteriacea, Pseudomonas, Chlamydia Mycoplasma & Legionella $10 Table-5: Half-Lives, Dosage form, microorganisms coverage and Price of Selected Antibiotics Commonly Used for Prophylaxis PowerPoint Presentation: Cefazolin beneﬁts from a benign adverse-event proﬁle , simple dosing , and low cost . Cefazolin is the preferred prophylactic agent for most clean procedures, including cardiac, vascular, and orthopedic procedures. Also the risk of cefazolin cross- allergenicity to penicillin is minimal These aspects have made cefazolin the mainstay for surgical prophylaxis of extra-abdominal procedures. For patients with a B- lactam allergy, clindamycin or vancomycin can be used as an alternative. PowerPoint Presentation: Vancomycin should be given within 2 hours prior to surgical incision. If duration of surgical procedure is >4 hours, patient should receive a second prophylactic dose intraoperatively. Total duration must be 24 hours for noncardiothoracic surgery and 48 hours for cardiothoracic surgery. Consider 2 grams in patients >100 kg. Decision to Use Antimicrobial Prophylaxis: Decision to Use Antimicrobial Prophylaxis The selected prophylactic agent should be directed against likely infecting organisms, but need not eradicate every potential pathogen . It should be bear in mind that, the goal of prophylaxis is to decrease bacterial counts below critical levels necessary to cause infection. PowerPoint Presentation: Newer antimicrobials have not demonstrated superiority in the prevention of SSI and should be reserved for treatment only. Broad-spectrum agents, such as Carbapenems ( antipseudomonal penicillins ), 3 rd & 4 th generation cephalosporins, should be avoided for prophylaxis because they are no more effective than cefazolin and may alter microbial flora, increasing the emergence of microbial resistance to these otherwise valuable agents. Route of Administration: Route of Administration In general, oral administration of surgical antimicrobial prophylaxis is not recommended because of unreliable or poor absorption of oral agents in the anesthetized bowel . however, oral agents function effectively as GI decontaminants The concentration of bacteria in the colon may approach 10 16 bacteria/mm 3 and colorectal procedures , carry a relatively high risk of postoperative infection . Antimicrobial regimens with activity against the mixture of aerobic and anaerobic bacteria are effective in preventing postoperative SSIs in these area PowerPoint Presentation: The most widely used oral antimicrobial regimen directed against the fecal flora is 1 g each of the nonabsorbable antibiotics neomycin sulfate ( for gram-negative aerobes ) and erythromycin base ( for anaerobes ), given 1 day before surgery at the times indicated. Mechanical bowel cleansing, such as with polyethylene glycol-electrolyte or sodium phosphate lavage solution , should precede the above regimen Effective oral alternatives to the above regimen include Metronidazole ± neomycin/kanamycin, or kanamycin + erythromycin; but no clinical warranty Timing of Antimicrobial Administration : Timing of Antimicrobial Administration For maximal efficacy , an antibiotic should be present in therapeutic concentrations at the incision site as early as possible during the decisive period and continuing until the wound is closed. However, an antibiotic administered postoperatively cannot achieve therapeutic concentrations during the decisive period, and infection rates are similar to those in patients who receive no antibiotics. But some studies showed that the incidence of endometritis after C/S is decreased significantly by postoperative administration of antibiotics. . PowerPoint Presentation: Therefore, prophylactic antibiotics should be administered before the surgical procedure in the OR before or during the induction of anesthesia . Prophylactic antibiotics are most effective when given during the 1-hour period before the surgical incision is made, and rates of infection increase significantly if antibiotics are administered >1 hour preoperatively or any time postoperatively. Dosing and Redosing: Dosing and Redosing The goal of antimicrobial dosing for surgical prophylaxis is to maintain antibiotic concentrations above the MIC of suspected organisms for the duration of the operation. Dosing recommendations can vary between institutions and guidelines. Clinical judgment should be exercised regarding dose modiﬁcations for renal function, age, and especially weight. Obese patients often require higher doses than do non-obese patients. PowerPoint Presentation: Guidelines suggest that if an operation exceeds two half-lives of the selected antimicrobial, then another dose should be administered. Repeat dosing has been shown to lower rates of SSI. The clinician should have extra doses of antibiotic ready in case an operation lasts longer than planned. Duration of Administration: Duration of Administration The shortest effective prophylactic course of antibiotics should be used; i.e., single dose preoperatively or not more than 24 hours postoperatively for most procedures Postoperative doses after wound closure are usually not required and may increase the risk of resistance. Single-dose prophylaxis , a viable option for many surgical procedures , is controversial for cardiac procedures . In practice, cardiothoracic antimicrobial prophylaxis often is continued 48 hours after surgery. (but>48hrs emergence of resistance) Signs of Surgical Site Infection: Signs of Surgical Site Infection Typically, an infected incision site wound is red, inflamed, and purulent . The purulent drainage should be cultured Empiric therapy directed against the most likely pathogens should be instituted while awaiting culture and sensitivity test results. Although most incision site infections are clinically apparent shortly after surgery (within 30 days), some deep-seated infections present indolently over weeks to months When implants are involved, infections occurring up to a year after surgery may be related to the operation. Risks of Indiscriminate Antimicrobial Use: Risks of Indiscriminate Antimicrobial Use The risks of indiscriminate use of antimicrobials to a given patient include the potential for adverse effects and superinfection . The administration of any β-lactam agent poses the risk of a hypersensitivity reaction, and many antibiotics, including cefoxitin, are known to predispose patients to Clostridium difficile-associated disease (pseudomembranous colitis) . In addition, widespread or prolonged use of antimicrobial agents increases the potential for the development or selection of resistant organisms in a given patient or other patients who may acquire a pathogen nosocomially. What are the “Emerging Pathogens”? -due to Indiscriminate Antimicrobial Use: What are the “Emerging Pathogens”? -due to Indiscriminate Antimicrobial Use Multi-Drug Resistant Gram Negative Bacilli (MDR) ESBLs* ( E. coli, Klebsiella) P. aeruginosa Acinetobacter spp. Vancomycin-Resistant Enterococci (VRE) Enterococcus faecium Methicillin-Resistant S. aureus (MRSA) Clostridium difficile -Associated Disease *Extended Spectum Beta-Lactmase Optimizing Surgical Antimicrobial Prophylaxis: Optimizing Surgical Antimicrobial Prophylaxis Antibiotic control strategies have improved the appropriate use of antimicrobial agents for surgical prophylaxis. The implementation of an automatic stop-order policy for surgical prophylaxis has reduced the duration of antimicrobial prophylaxis dramatically. These stop-order policies can be printed directly onto an antibiotic order form. The process can help improve antibiotic appropriateness and timing of administration. PowerPoint Presentation: In collaboration with other health care providers, the pharmacy department of health care organizations is responsible for optimizing the timing , choice , and duration of antimicrobial surgical prophylaxis. Education of surgical, anesthesia, and nursing staff, supported by hospital policy changes initiated by pharmacists improved appropriate timing from 68% to 97% and resulted in significant cost avoidance. PowerPoint Presentation: TREATMENT Goals of Surgical Prophylaxis: Goals of Surgical Prophylaxis Ideally, an anti-infective drug for surgical prophylaxis should achieve the following goals: (1) prevent postoperative infection of the surgical site, (2) prevent postoperative infectious morbidity and mortality, (3) reduce the duration and cost of health care, (4) produce no adverse effects, and (5) have no adverse consequences for the microbial flora of the patient or the hospital. PowerPoint Presentation: Table-6: Suggested Prophylactic Antimicrobial Regimens for Surgical Procedures in Adults Procedure Predominant Organism(s) Antibiotic Regimen (Alternative) Adult Preoperative IV Dose (Alternative) a Cardiac (all with sternotomy, cardio-pulmonary bypass) Staphylococcus aureus, Staphylococcus epidermidis Cefazolin (Vancomycin) 1 g (1 g) Thoracic S. aureus , S. epidermidis , gram-negative enterics Cefazolin (Vancomycin) 1 g (1 g) Vascular (aortic resection, groin incision, prosthesis) S. aureus, S. epidermidis, gram-negative enterics Cefazolin (Vancomycin) 1 g (1 g) Orthopedic (total joint replacement, internal fixation of fractures) S. aureus, S. epidermidis Cefazolin (Vancomycin) 1 g (1 g) Neurosurgery S. aureus, S. epidermidis Cefazolin (Vancomycin) 1 g (1 g) Table-6: cont’d: Table-6: cont’d Head and neck S. aureus, oral anaerobes, streptococci Cefazolin (clindamycin/ gentamicin) 2 g (600 mg clindamycin/ 1.5 mg/kg gentamicin) Gastroduodenal (only for procedures entering stomach) Gram-negative enterics, S. aureus, mouth flora Cefazolin 1 g Colorectal Gram-negative enterics, anaerobes ( Bacteroides fragilis ), enterococci Oral neomycin-erythromycin base (Cefoxitin) 1 g each at 1 PM, 2 PM, and 11 PM day before surgery (1 g) Appendectomy (uncomplicated) Gram-negative enterics, anaerobes ( B. fragilis ) Cefoxitin 1–2 g Biliary tract (only for high-risk procedures) Gram-negative enterics, Enterococcus faecalis, Clostridia Cefazolin 1 g Table-6: cont’d: Cesarean section Group B streptococci, enterococci, anaerobes, gram-negative enterics Cefazolin 2 g after umbilical cord clamped Hysterectomy Group B streptococci, enterococci, anaerobes, gram-negative enterics Cefazolin or cefoxitin 1 g Genitourinary (only for high-risk procedures) Gram-negative enterics, enterococci Ciprofloxacin 400 mg Cef azolin should be dosed at 2 g in patients >80 kg. Source: Koda-Kimble . Applied Therapeutics: Table-6: cont’d Table-7: ASHP Antimicrobial Prophylaxis Recommendations for Surgical Transplantation in Adults: Table-7: ASHP Antimicrobial Prophylaxis Recommendations for Surgical Transplantation in Adults Source: ASHP Guideline for antimicrobial prophylaxis in surgery Table-8: Antimicrobial Regimens for Surgical Prophylaxis in Pediatric Patients: Table-8: Antimicrobial Regimens for Surgical Prophylaxis in Pediatric Patients Table-8: cont’d: Table-8: cont’d Table-8: cont’d: Table-8: cont’d Table-8: cont’d: Table-8: cont’d PowerPoint Presentation: OUTCOME EVALUATION PowerPoint Presentation: The clinician should consistently follow-up post-operative patients and screen for any sign of SSI . According to CDC criteria, SSI may appear up to 30 days after an operation and up to 1 year if a prosthesis is implanted. This period often extends beyond hospitalization so patients should be educated on warning signs of SSI and be encouraged to contact a clinician immediately if necessary. The presence of fever or leukocytosis in the immediate post-operative period does not constitute SSI and should resolve with proper patient care. PowerPoint Presentation: Distal infections , such as pneumonia, are not considered SSIs even if these infections occur in the 30-day period. The appearance of the surgical site should be checked regularly and any changes documented (e.g., erythema, drainage, or pus ). The presence of pus or other signs suggestive of SSI must be treated accordingly. Any wound requiring incision and drainage is considered an SSI regardless of appearance. Prompt cultures should be collected and appropriate antimicrobial therapy initiated to reduce any chance of morbidity and mortality. Alternative Methods to Decrease SSI: Alternative Methods to Decrease SSI Several non-antimicrobial methods have been studied for reducing the risk of SSI. Kurz and associates found that providing supplemental warming to patients (36.6°C or 98°F) during the intraoperative period reduced infection rates compared to control patients (34.7°C or 94.5°F). Van den Berghe and co-workers studied the impact of intensive glucose control [80 to 110 mg/dL (4.44 to 6.1 mmol/L)] versus conventional control [glucose less than 210 mg/dL (less than 11.7 mmol/L)] and found an advantage for intensive glucose control in reducing infections in critically ill patients. PowerPoint Presentation: Greif and colleagues found that patients randomized to 80% inspired oxygen had lower SSI rates compared to patients on 30% oxygen after colorectal resection. Antibiotic-impregnated bone cement is being used as an adjunct or alternative to traditional antimicrobial prophylaxis. A study by Chiu and associates found cefuroxime-impregnated cement lowered the risk of deep infection after primary total knee arthoplasty. Other studies have been inconclusive regardng superiority of antibiotic-impregnated bone cement versus conventional therapies. PowerPoint Presentation: The problem of using antibiotic-impregnated bone cement is:- The long-term durability is unknown, antibiotics may reduce the tensile strength of bone cement Lack of in-depth clinical trials strengthen future benefit of the procedure Because of these facts, it does not warrant to be used as an alternative to surgical antimicrobial prophylaxis PowerPoint Presentation: LITERATURES & GUIDELINES REVIEW PowerPoint Presentation: Several studies have been performed investigating the utility of prophylactic antibiotics in surgery. With regards to surgical prophylaxis, the data from these studies support several recurring themes: Plenty of articles & guidelines found that ‘ a single preoperative dose of antibiotic is as effective as a 5-day course of postoperative therapy assuming an uncomplicated procedure’ & Almost all articles & guidelines are complimentary in that ‘ Prophylactic antibiotics should target the anticipated organisms ’ PowerPoint Presentation: Most guidelines & literatures still agreed on:- complicated, contaminated, or dirty procedures should receive additional postoperative antimicrobial coverage During prolonged procedures, antibiotic prophylaxis should be readministered every 3-4 hours Prophylactic antibiotics should be administered within 1 hour prior to incision PowerPoint Presentation: Patient Care and Monitoring PowerPoint Presentation: Conduct a thorough medication history including prescription and non-prescription medications as well as herbals and vitamins. Verify the patient’s allergy history and the type of reaction experienced. Attempt to discern between true allergy and adverse event. β-Lactam–allergic patients may receive clindamycin, vancomycin, or other antimicrobials. The patient should be monitored for signs of an allergic reaction during the operation. The patient should be monitored for signs and symptoms of infection post-operatively. Patients being discharged should be counseled on recognizing signs and symptoms of SSI. References: References MARIE A. CHISHOLM-BURNS.PHARMACOTHERAPY PRINCIPLES & PRACTICE. CHISHOLM-BURNS MA, editor: The McGraw-Hill Companies, Inc. ; 2008. Joseph T. DiPiro P, Executive Dean and Professor, South Carolina College of Pharmacy, University of South Carolina. Pharmacotherapy A Pathophysiologic Approach. Seventh Edition ed.: McGraw-Hill; 2008. Koda-Kimble MAY, Lloyd Yee. Applied Therapeutics: The Clinical Use Of Drugs, 9th Edition. Koda-Kimble MAY, Lloyd Yee, editor: Copyright ©2009 Lippincott Williams & Wilkins; 2009. PowerPoint Presentation: RONALD K. WOODS, M.D., PH.D., and E. PATCHEN DELLINGER, M.D.: Current Guidelines for Antibiotic Prophylaxis of Surgical Wounds; University of Washington Medical Center, Seattle, Washington: Am Fam Physician. 1998 Jun 1;57(11):2731-2740. D.Jonkers et al: Influence of cefazolin prophyaxis and hospitalization on the prevalence of antibiotic resistant bacteria in the faecal flora; Jornal of Antimicrobial Chemotherapy(2002) 49, 567-571 ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery 2002 Aschalew, Isolation of Bacterial Pathogens from Patients with Postoperative Surgical site infections and possible sources of infections at university of Gondar hospital, northwest Ethiopia, 2011 Questions?: Questions? PowerPoint Presentation: Thank You!!!