PHARMACOLOGY FACTS
Antimicrobial Prophylaxis for Surgery—2014 Update Julie Golembiewski, PharmD ALTHOUGH MANY FACTORS contribute to the development of a surgical site infection (SSI), appropriate antimicrobial prophylaxis is an effective intervention to prevent postoperative wound infection.1 Antimicrobial prophylaxis is beneficial for surgical procedures associated with a high infection rate (eg, colorectal surgery) or significant consequences if an infection develops (eg, prosthetic implant), as well as for patients who are at high risk for developing an infection (eg, impaired immune response). In 2002, the Centers for Medicare and Medicaid Services and the Centers for Disease Control and Prevention identified three measures for antimicrobial prophylaxis in surgery: (1) the prophylactic antibiotic is given within 1 hour before surgical incision, (2) an appropriate antibiotic is administered, and (3) the prophylactic antibiotic is discontinued within 24 hours after surgery (48 hours for cardiac surgery).2 These measures have since been adopted by the Surgical Care Improvement Project, Joint Commission, and Physicians Quality Reporting System as performance measures with financial implications for physicians and hospitals.3 In 2013, the American Society of Health System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and Society for Healthcare Epidemiology of America published guidelines that provide a standardized approach to use of antimicrobial agents for the prevention of SSIs.4 This column summarizes key components of this guideline, consult the publication for complete information and recommendations. Julie Golembiewski, PharmD, is a Clinical Associate Professor, Departments of Hospital Pharmacy and Anesthesiology, University of Illinois Hospital & Health Sciences System, Chicago, IL. Conflict of interest: None to report. Address correspondence to Julie Golembiewski, Departments of Hospital Pharmacy and Anesthesiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, Suite 3200, MC 515, Chicago, IL 60612-7239; e-mail address: [email protected]. Ó 2014 by American Society of PeriAnesthesia Nurses 1089-9472/$36.00 http://dx.doi.org/10.1016/j.jopan.2014.01.001
Journal of PeriAnesthesia Nursing, Vol 29, No 2 (April), 2014: pp 155-158
Administering the prophylactic antibiotic within 1 hour before surgical incision ensures that serum and tissue antimicrobial concentrations exceed the minimum inhibitor concentration (MIC) of the most likely infecting organisms at the time of surgical incision.4-6 When a fluoroquinolone (eg, levofloxacin, ciprofloxacin) or vancomycin is indicated, the infusion should begin within 2 hours before surgical incision as these agents require a 1-hour infusion rate to minimize the risk of hypotension. Antimicrobial serum and tissue concentrations should remain above the MIC of the potential infecting organism throughout the entire time, the surgical site is open to minimize the risk of a SSI.7 Koopman et al 8 examined serum cefazolin concentrations within 15 minutes of wound closure after a single prophylactic dose in adults undergoing elective surgery. Approximately onethird of the subjects had cefazolin serum concentrations of , 4 mcg/mL, which is the MIC for 90% of methicillin-susceptible Staphylococcus aureus. Multiple regression analysis was used to obtain an equation to calculate cefazolin serum concentration as a function of the number of hours after the prophylactic dose. Using this equation, the cefazolin serum concentration is expected to be below 4 mcg/mL in 2.5 to 4.6 hours (approximately two half-lives) after administration of the initial prophylactic dose. Therefore, intraopertive redosing is necessary to ensure adequate antimicrobial concentrations at the time of wound closure when the duration of surgery exceeds two half-lives of the antimicrobial agent or there is excessive blood loss (eg, .1,500 mL).4 Although antimicrobial dosing in children is based on body weight, antimicrobial dosing in adults is usually standardized (eg, 1 g, 2 g) rather than body weight. For some antimicrobial agents, however, serum and tissue concentrations may be different in obese or morbidly obese patients than in normal weight patients. Forse et al9 demonstrated that administration of 2 g of cefazolin to
155
156
Table 1. Recommended Doses, Redosing Intervals, and Place in Therapy for Select Antimicrobials for Surgical Prophylaxis* Antimicrobial Cefazolin
Recommended Adult Dose 2 g; 3 g for patients $120 kg
Recommended Pediatric Dosey
Recommended Redosing Intervalz (h)
30 mg/kg
4
Cefoxitin
2g
40 mg/kg
2
Cefotetan
2g
40 mg/kg
6
900 mg
10 mg/kg
6
2.5 mg/kg based on dosing weight{ 10 mg/kg
NA
NA
500 mg
15 mg/kg
NA
15 mg/kg
15 mg/kg
NA
Clindamycin
Gentamicin
Levofloxacin
Metronidazole
Vancomycin
5 mg/kg based on dosing weight (single dose only){ 500 mg
Place in Therapyx Drug of choice for most procedures; add metronidazole for appendectomy, obstructed small intestine, colorectal, and cleancontaminated head and neck procedures (except tonsillectomy and endoscopic sinus) Prophylaxis for appendectomy, biliary tract, obstructed small intestine, colorectal, hysterectomy, and clean-contaminated urologic procedures Prophylaxis for appendectomy, biliary tract, obstructed small intestine, colorectal, and hysterectomy procedures Alternative to cefazolin when source of infection is skin flora only; add gentamicin for biliary tract, gastroduodenal, appendectomy, nonobstructed small intestine, Cesarean delivery, or hysterectomy When combined with clindamycin, alternative to cefazolin for biliary tract, gastroduodenal, appendectomy, nonobstructed small intestine, Cesarean delivery, or hysterectomy; select urologic surgery Prophylaxis for select urologic surgery; alternative with clindamycin or metronidazole for biliary tract, appendectomy, small intestine, colorectal, or hysterectomy; alternative with clindamycin for gastroduodenal procedures When combined with cefazolin, surgical prophylaxis for appendectomy, obstructed small intestine, colorectal, and clean-contaminated head and neck procedures Alternative to cefazolin when source of infection is skin flora only; add gentamicin for biliary tract, gastroduodenal, or hysterectomy JULIE GOLEMBIEWSKI
*Adapted from Bratzler et al.4 Consult published guidelines for complete recommendations. Children aged 1 to 18 years; maximum pediatric dose should not exceed usual adult dose. z Not a complete list; consult published guidelines for full recommendations. x For patients with normal renal function; NA 5 redosing is not necessary unless it is an unusually long surgical procedure (eg, .12 hours). { Generally limited to a single preoperative dose based on actual body weight unless patient’s actual body weight is more than 20% above ideal body weight. For patient’s weighing more than 20% above ideal body weight, use dosing weight. Dosing weight 5 ideal body weight 1 0.4 (actual weight 2 ideal body weight). y
PHARMACOLOGY FACTS
157
morbidly obese patients resulted in similar serum and adipose tissue concentrations to the concentrations in normal weight patients who received a 1 g dose. Edmiston et al10 examined the serum and tissue levels after the administration of 2 g of cefazolin in 30 to 60 minutes before surgical incision followed by a second dose 3 hours later in morbidly obese patients undergoing Roux-en-Y gastric bypass. Subjects were assigned to one of three groups: Group A 5 body mass index (BMI), 40 to 49; Group B 5 BMI, 50 to 59; and Group C 5 BMI, $60. Therapeutic tissue concentrations were achieved in only 48% (Group A), 29% (Group B), and 10% (Group C) of subjects. Therefore, a standard adult cefazolin dose of 2 and 3 g for patients weighing $120 kg is warranted4,11 (Table 1). Selection of the antimicrobial agent is based on its activity for the most likely infecting organisms. For clean procedures in which the wounds are closed and the respiratory, alimentary, genital or uninfected urinary tracts have not been entered, the most likely organisms causing SSIs are skin flora (Staphylococcus epidermidis and S. aureus). Cefazolin is the prophylactic antibiotic of choice for these clean surgical procedures. Cefazolin is active against staphylococci and has a favorable side effect profile. Clindamycin and vancomycin are alternative agents in patients with a b-lactam allergy. To prevent and control resistance, vancomycin prophylaxis should not be routine but may be considered when the risk of methicillin-resistant staphylococcus aureus is high.4,12 For clean contaminate procedures (eg, abdominal procedures), gram-negative rods and
enterococci may cause SSIs in addition to skin flora. Cefazolin is active against most, but not all, gramnegative rods. For surgical procedures involving the appendix or colon for example, metronidazole should be administered (with cefazolin) for its activity against anaerobic gram-negative rods (Table 1). In general, antimicrobial agents with the narrowest spectrum of activity for preventing a SSI are recommended.4 Antimicrobial prophylaxis can alter the individual and institutional bacterial flora leading to increased bacterial resistance. A longer duration of antimicrobial prophylaxis and the administration of multiple antimicrobial agents increase the risk for development of Clostridium difficile–associated colitis.13 Postoperative antimicrobial administration should not exceed 24 hours (48 hours in cardiac surgery). Growing evidence supports not administering an antimicrobial agent postoperatively once the wound is closed for most surgical procedures.6 The guidelines also clarify that ‘‘There are no data to support the continuation of antimicrobial prophylaxis until all indwelling drains and intravascular catheters are removed.’’4 Many factors increase the risk of SSI. Patient factors such as diabetes and obesity are not able to be modified at the time of surgery. Appropriate selection and administration of prophylactic antimicrobials, however, can prevent an estimated 40% to 60% of SSIs.11 Attention should be given to weight-based dosing and appropriate redosing of antimicrobials to ensure adequate serum and tissue levels from the time of surgical incision to wound closure.
References 1. Bowater RJ, Stirling SA, Lilford RJ. Is antibiotic prophylaxis in surgery a generally effective intervention? Testing a generic hypothesis over a set of meta-analyses. Ann Surg. 2009;249: 551-556. 2. Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38: 1706-1715. 3. Bratzler DW, Hunt DR. The surgical infection prevention and surgical care improvement projects: National initiatives to improve outcomes for patients having surgery. Clin Infect Dis. 2006;43:322-330. 4. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70:195-283.
5. Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration and the risk of surgical wound infection. N Engl J Med. 1992;326:281-286. 6. Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett. 2009;7:47-52. 7. Zelenitsky SA, Ariano RE, Harding GK, et al. Antibiotic pharmacodynamics in surgical prophylaxis: An association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother. 2002;46:3026-3030. 8. Koopman E, Nix DE, Erstad BL, et al. End-of-procedure cefazolin concentrations after administration for prevention of surgicalsite infection. Am J Health Syst Pharm. 2007;64:1927-1934. 9. Forse RA, Karam B, MacLean LD, Christou NV. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery. 1989;106:750-757.
158
10. Edmiston CE, Krepel C, Kelly H, et al. Perioperative antibiotic prophylaxis in the gastric bypass patient: Do we achieve therapeutic levels? Surgery. 2004;136:738-747. 11. Institute for Healthcare Improvement. Changes to prevent surgical site infection: Use prophylactic antibiotics appropriately. Available at: http://www.ihi.org/IHI/Topics/PatientSafety/SurgicalSiteInfections/Changes/SSI1Use1Prophylactic1Antibiotics1 Appropriately.htm. Accessed January 3, 2014
JULIE GOLEMBIEWSKI 12. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection. Infect Control Hosp Epidemiol. 1999;20:250-278. 13. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Disease Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
Antimicrobial Prophylaxis for Surgery—2014 Update Julie Golembiewski, PharmD ALTHOUGH MANY FACTORS contribute to the development of a surgical site infection (SSI), appropriate antimicrobial prophylaxis is an effective intervention to prevent postoperative wound infection.1 Antimicrobial prophylaxis is beneficial for surgical procedures associated with a high infection rate (eg, colorectal surgery) or significant consequences if an infection develops (eg, prosthetic implant), as well as for patients who are at high risk for developing an infection (eg, impaired immune response). In 2002, the Centers for Medicare and Medicaid Services and the Centers for Disease Control and Prevention identified three measures for antimicrobial prophylaxis in surgery: (1) the prophylactic antibiotic is given within 1 hour before surgical incision, (2) an appropriate antibiotic is administered, and (3) the prophylactic antibiotic is discontinued within 24 hours after surgery (48 hours for cardiac surgery).2 These measures have since been adopted by the Surgical Care Improvement Project, Joint Commission, and Physicians Quality Reporting System as performance measures with financial implications for physicians and hospitals.3 In 2013, the American Society of Health System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and Society for Healthcare Epidemiology of America published guidelines that provide a standardized approach to use of antimicrobial agents for the prevention of SSIs.4 This column summarizes key components of this guideline, consult the publication for complete information and recommendations. Julie Golembiewski, PharmD, is a Clinical Associate Professor, Departments of Hospital Pharmacy and Anesthesiology, University of Illinois Hospital & Health Sciences System, Chicago, IL. Conflict of interest: None to report. Address correspondence to Julie Golembiewski, Departments of Hospital Pharmacy and Anesthesiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, Suite 3200, MC 515, Chicago, IL 60612-7239; e-mail address: [email protected]. Ó 2014 by American Society of PeriAnesthesia Nurses 1089-9472/$36.00 http://dx.doi.org/10.1016/j.jopan.2014.01.001
Journal of PeriAnesthesia Nursing, Vol 29, No 2 (April), 2014: pp 155-158
Administering the prophylactic antibiotic within 1 hour before surgical incision ensures that serum and tissue antimicrobial concentrations exceed the minimum inhibitor concentration (MIC) of the most likely infecting organisms at the time of surgical incision.4-6 When a fluoroquinolone (eg, levofloxacin, ciprofloxacin) or vancomycin is indicated, the infusion should begin within 2 hours before surgical incision as these agents require a 1-hour infusion rate to minimize the risk of hypotension. Antimicrobial serum and tissue concentrations should remain above the MIC of the potential infecting organism throughout the entire time, the surgical site is open to minimize the risk of a SSI.7 Koopman et al 8 examined serum cefazolin concentrations within 15 minutes of wound closure after a single prophylactic dose in adults undergoing elective surgery. Approximately onethird of the subjects had cefazolin serum concentrations of , 4 mcg/mL, which is the MIC for 90% of methicillin-susceptible Staphylococcus aureus. Multiple regression analysis was used to obtain an equation to calculate cefazolin serum concentration as a function of the number of hours after the prophylactic dose. Using this equation, the cefazolin serum concentration is expected to be below 4 mcg/mL in 2.5 to 4.6 hours (approximately two half-lives) after administration of the initial prophylactic dose. Therefore, intraopertive redosing is necessary to ensure adequate antimicrobial concentrations at the time of wound closure when the duration of surgery exceeds two half-lives of the antimicrobial agent or there is excessive blood loss (eg, .1,500 mL).4 Although antimicrobial dosing in children is based on body weight, antimicrobial dosing in adults is usually standardized (eg, 1 g, 2 g) rather than body weight. For some antimicrobial agents, however, serum and tissue concentrations may be different in obese or morbidly obese patients than in normal weight patients. Forse et al9 demonstrated that administration of 2 g of cefazolin to
155
156
Table 1. Recommended Doses, Redosing Intervals, and Place in Therapy for Select Antimicrobials for Surgical Prophylaxis* Antimicrobial Cefazolin
Recommended Adult Dose 2 g; 3 g for patients $120 kg
Recommended Pediatric Dosey
Recommended Redosing Intervalz (h)
30 mg/kg
4
Cefoxitin
2g
40 mg/kg
2
Cefotetan
2g
40 mg/kg
6
900 mg
10 mg/kg
6
2.5 mg/kg based on dosing weight{ 10 mg/kg
NA
NA
500 mg
15 mg/kg
NA
15 mg/kg
15 mg/kg
NA
Clindamycin
Gentamicin
Levofloxacin
Metronidazole
Vancomycin
5 mg/kg based on dosing weight (single dose only){ 500 mg
Place in Therapyx Drug of choice for most procedures; add metronidazole for appendectomy, obstructed small intestine, colorectal, and cleancontaminated head and neck procedures (except tonsillectomy and endoscopic sinus) Prophylaxis for appendectomy, biliary tract, obstructed small intestine, colorectal, hysterectomy, and clean-contaminated urologic procedures Prophylaxis for appendectomy, biliary tract, obstructed small intestine, colorectal, and hysterectomy procedures Alternative to cefazolin when source of infection is skin flora only; add gentamicin for biliary tract, gastroduodenal, appendectomy, nonobstructed small intestine, Cesarean delivery, or hysterectomy When combined with clindamycin, alternative to cefazolin for biliary tract, gastroduodenal, appendectomy, nonobstructed small intestine, Cesarean delivery, or hysterectomy; select urologic surgery Prophylaxis for select urologic surgery; alternative with clindamycin or metronidazole for biliary tract, appendectomy, small intestine, colorectal, or hysterectomy; alternative with clindamycin for gastroduodenal procedures When combined with cefazolin, surgical prophylaxis for appendectomy, obstructed small intestine, colorectal, and clean-contaminated head and neck procedures Alternative to cefazolin when source of infection is skin flora only; add gentamicin for biliary tract, gastroduodenal, or hysterectomy JULIE GOLEMBIEWSKI
*Adapted from Bratzler et al.4 Consult published guidelines for complete recommendations. Children aged 1 to 18 years; maximum pediatric dose should not exceed usual adult dose. z Not a complete list; consult published guidelines for full recommendations. x For patients with normal renal function; NA 5 redosing is not necessary unless it is an unusually long surgical procedure (eg, .12 hours). { Generally limited to a single preoperative dose based on actual body weight unless patient’s actual body weight is more than 20% above ideal body weight. For patient’s weighing more than 20% above ideal body weight, use dosing weight. Dosing weight 5 ideal body weight 1 0.4 (actual weight 2 ideal body weight). y
PHARMACOLOGY FACTS
157
morbidly obese patients resulted in similar serum and adipose tissue concentrations to the concentrations in normal weight patients who received a 1 g dose. Edmiston et al10 examined the serum and tissue levels after the administration of 2 g of cefazolin in 30 to 60 minutes before surgical incision followed by a second dose 3 hours later in morbidly obese patients undergoing Roux-en-Y gastric bypass. Subjects were assigned to one of three groups: Group A 5 body mass index (BMI), 40 to 49; Group B 5 BMI, 50 to 59; and Group C 5 BMI, $60. Therapeutic tissue concentrations were achieved in only 48% (Group A), 29% (Group B), and 10% (Group C) of subjects. Therefore, a standard adult cefazolin dose of 2 and 3 g for patients weighing $120 kg is warranted4,11 (Table 1). Selection of the antimicrobial agent is based on its activity for the most likely infecting organisms. For clean procedures in which the wounds are closed and the respiratory, alimentary, genital or uninfected urinary tracts have not been entered, the most likely organisms causing SSIs are skin flora (Staphylococcus epidermidis and S. aureus). Cefazolin is the prophylactic antibiotic of choice for these clean surgical procedures. Cefazolin is active against staphylococci and has a favorable side effect profile. Clindamycin and vancomycin are alternative agents in patients with a b-lactam allergy. To prevent and control resistance, vancomycin prophylaxis should not be routine but may be considered when the risk of methicillin-resistant staphylococcus aureus is high.4,12 For clean contaminate procedures (eg, abdominal procedures), gram-negative rods and
enterococci may cause SSIs in addition to skin flora. Cefazolin is active against most, but not all, gramnegative rods. For surgical procedures involving the appendix or colon for example, metronidazole should be administered (with cefazolin) for its activity against anaerobic gram-negative rods (Table 1). In general, antimicrobial agents with the narrowest spectrum of activity for preventing a SSI are recommended.4 Antimicrobial prophylaxis can alter the individual and institutional bacterial flora leading to increased bacterial resistance. A longer duration of antimicrobial prophylaxis and the administration of multiple antimicrobial agents increase the risk for development of Clostridium difficile–associated colitis.13 Postoperative antimicrobial administration should not exceed 24 hours (48 hours in cardiac surgery). Growing evidence supports not administering an antimicrobial agent postoperatively once the wound is closed for most surgical procedures.6 The guidelines also clarify that ‘‘There are no data to support the continuation of antimicrobial prophylaxis until all indwelling drains and intravascular catheters are removed.’’4 Many factors increase the risk of SSI. Patient factors such as diabetes and obesity are not able to be modified at the time of surgery. Appropriate selection and administration of prophylactic antimicrobials, however, can prevent an estimated 40% to 60% of SSIs.11 Attention should be given to weight-based dosing and appropriate redosing of antimicrobials to ensure adequate serum and tissue levels from the time of surgical incision to wound closure.
References 1. Bowater RJ, Stirling SA, Lilford RJ. Is antibiotic prophylaxis in surgery a generally effective intervention? Testing a generic hypothesis over a set of meta-analyses. Ann Surg. 2009;249: 551-556. 2. Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis. 2004;38: 1706-1715. 3. Bratzler DW, Hunt DR. The surgical infection prevention and surgical care improvement projects: National initiatives to improve outcomes for patients having surgery. Clin Infect Dis. 2006;43:322-330. 4. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70:195-283.
5. Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administration and the risk of surgical wound infection. N Engl J Med. 1992;326:281-286. 6. Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett. 2009;7:47-52. 7. Zelenitsky SA, Ariano RE, Harding GK, et al. Antibiotic pharmacodynamics in surgical prophylaxis: An association between intraoperative antibiotic concentrations and efficacy. Antimicrob Agents Chemother. 2002;46:3026-3030. 8. Koopman E, Nix DE, Erstad BL, et al. End-of-procedure cefazolin concentrations after administration for prevention of surgicalsite infection. Am J Health Syst Pharm. 2007;64:1927-1934. 9. Forse RA, Karam B, MacLean LD, Christou NV. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery. 1989;106:750-757.
158
10. Edmiston CE, Krepel C, Kelly H, et al. Perioperative antibiotic prophylaxis in the gastric bypass patient: Do we achieve therapeutic levels? Surgery. 2004;136:738-747. 11. Institute for Healthcare Improvement. Changes to prevent surgical site infection: Use prophylactic antibiotics appropriately. Available at: http://www.ihi.org/IHI/Topics/PatientSafety/SurgicalSiteInfections/Changes/SSI1Use1Prophylactic1Antibiotics1 Appropriately.htm. Accessed January 3, 2014
JULIE GOLEMBIEWSKI 12. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection. Infect Control Hosp Epidemiol. 1999;20:250-278. 13. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Disease Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
