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Tr e a t m e n t

Vol. 2 (Issue 20)

Guidelines The Medical Letter from

April 2004

Published by The Medical Letter, Inc. 1000 Main Street New Rochelle, N.Y. 10801 www.medicalletter.org

Tables Choice of Drug

Page 28

®

Antimicrobial Prophylaxis for Surgery Antimicrobial prophylaxis can decrease the incidence of infection, particularly surgical site infection, after certain operations, but this benefit must be weighed against the risks of toxic and allergic reactions, emergence of resistant bacteria, adverse drug interactions, superinfection and cost. Medical Letter consultants generally recommend antimicrobial prophylaxis only for procedures with high infection rates, those involving implantation of prosthetic material, and those in which the consequences of infection are likely to be especially serious.

Some Exceptions – For procedures that might involve exposure to bowel anaerobes, including Bacteroides fragilis, cefotetan (Cefotan) or cefoxitin (Mefoxin, and others) are preferred because they are more active than cefazolin against these organisms. In institutions where methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative staphylococci are important post-operative pathogens, vancomycin (Vancocin, and others) can be used, but routine use of vancomycin for prophylaxis should be discouraged because it may promote emergence of vancomycin-resistant organisms and, at least in one study, was no better than cefazolin at preventing surgical site infection after cardiac surgery in a setting with a high prevalence of MRSA (R Finkelstein et al, J Thorac Cardiovasc Surg 2002; 123:326). Long preoperative hospitalizations are associated with increased risk of infection with an antibiotic-resistant organism; local resistance patterns should be taken into account.

Recommendations for prevention of surgical site infection are listed in the table that begins on page 28. Recommendations for prevention of bacterial endocarditis in patients with valvular heart disease, prosthetic heart valves or other cardiac abnormalities are not included here; this subject has been reviewed elsewhere (Medical Letter 2001; 43:98). CHOICE OF A PROPHYLACTIC AGENT

Not Recommended – Third-generation cephalosporins, such as cefotaxime (Claforan), ceftriaxone (Rocephin), cefoperazone (Cefobid), ceftazidime (Fortaz, and others), or ceftizoxime (Cefizox), and fourth-generation cephalosporins such as cefepime (Maxipime) should not be used for routine surgical prophylaxis because they are expensive, some are less active than cefazolin against staphylococci, their spectrum of activity

An effective prophylactic regimen should be directed against the most likely infecting organisms, but need not eradicate every potential pathogen. For most procedures, cefazolin (Ancef, and others), which has a moderately long plasma half-life and is active against most staphylococci and streptococci, has been effective.

EDITOR: Mark Abramowicz, M.D. DEPUTY EDITOR: Gianna Zuccotti, M.D., M.P.H., Weill Medical College of Cornell University CONSULTING EDITOR: Martin A. Rizack, M.D., Ph.D., Rockefeller University ASSOCIATE EDITORS: Donna Goodstein, Amy Faucard MANAGING EDITOR: Susie Wong CONTRIBUTING EDITOR: Philip D. Hansten, Pharm. D., University of Washington ADVISORY BOARD: Jules Hirsch, M.D., Rockefeller University; James D. Kenney, M.D., Yale University School of Medicine; Gerald L. Mandell, M.D., University of Virginia School of Medicine; Hans Meinertz, M.D., University Hospital, Copenhagen; Dan M. Roden, M.D., Vanderbilt School of Medicine; F. Estelle R. Simons, M.D., University of Manitoba; Neal H. Steigbigel, M.D., New York University School of Medicine EDITORIAL FELLOWS: Monika K. Shah, M.D., Columbia University College of Physicians and Surgeons; Jane P. Gagliardi, M.D., Duke University Medical Center EDITORIAL ADMINISTRATOR: Marianne Aschenbrenner PUBLISHER: Doris Peter, Ph.D. Copyright 2003. The Medical Letter, Inc. (ISSN 1541-2792)

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27

Antimicrobial Prophylaxis for Surgery CHOICE OF DRUG FOR PREVENTION OF SURGICAL SITE INFECTION Recommended drugs

Adult dosage before surgery1

Staphylococcus aureus, S. epidermidis

cefazolin or cefuroxime OR vancomycin3

1-2 grams IV2 1.5 grams IV2 1 gram IV

Enteric gram-negative bacilli, gram-positive cocci Enteric gram-negative bacilli, enterococci, clostridia Enteric gram-negative bacilli, anaerobes, enterococci

High risk4 only: cefazolin7 High risk5 only: cefazolin7 Oral: neomycin + erythromycin base6 OR metronidazole6 Parenteral: cefotetan or cefoxitin OR cefazolin + metronidazole7 cefoxitin or cefotetan OR cefazolin + metronidazole7 cefoxitin or cefotetan ± gentamicin7,8

Nature of operation

Common pathogens

Cardiac

Gastrointestinal Esophageal, gastroduodenal Biliary tract Colorectal

Appendectomy, non-perforated

Enteric gram-negative bacilli, anaerobes, enterococci

Ruptured viscus

Enteric gram-negative bacilli, anaerobes, enterococci Enteric gram-negative bacilli, enterococci

High risk9 only: ciprofloxacin

Cesarean section

Enteric gram-negative bacilli, anaerobes, Gp B strep, enterococci same as for hysterectomy

cefotetan or cefoxitin or cefazolin7 cefazolin

Abortion

same as for hysterectomy

First trimester, high risk10: aqueous penicillin G OR doxycycline Second trimester: cefazolin

Genitourinary

Gynecologic and Obstetric Vaginal, abdominal or laparoscopic hysterectomy

1-2 grams IV 1-2 grams IV

1-2 grams IV 1-2 grams IV 1-2 grams IV 0.5-1 grams IV 1-2 grams IV 1-2 grams IV 1-2 grams IV 0.5-1 grams IV 1-2 g IV q6h 1-2 g IV q12h 1.5 mg/kg IV q8h 500 mg PO or 400 mg IV 1-2 grams IV 1-2 grams IV 1-2 grams IV 1-2 grams IV after cord clamping 2 mill units IV 300 mg PO11 1-2 grams IV

1. Parenteral prophylactic antimicrobials can be given as a single IV dose begun 60 minutes or less before the operation. For prolonged operations, additional intraoperative doses should be given at intervals 1-2 times the half-life of the drug for the duration of the procedure. If vancomycin or a fluoroquinolone is used, the infusion should be started 60-120 minutes before incision in order to minimize the possibility of an infusion reaction close to the time of induction of anesthesia and to have adequate tissue levels at the time of incision. 2. Some consultants recommend an additional dose when patients are removed from bypass during open-heart surgery. 3. For hospitals in which methicillin-resistant S. aureus and S. epidermidis are a frequent cause of postoperative wound infection, for patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with diphenhydramine (Benadryl, and others) and further slowing of the infusion rate may be helpful. For procedures in which enteric gram-negative bacilli are likely pathogens, such as vascular surgery involving a groin incision, cefazolin or cefuroxime should be included in the prophylaxis regimen for patients not allergic to cephalosporins; ciprofloxacin, levofloxacin (750 mg), gentamicin, or aztreonam, each one in combination with vancomycin, can be used in patients who cannot tolerate a cephalosporin. 4. Morbid obesity, esophageal obstruction, decreased gastric acidity or gastrointestinal motility. 5. Age >70 years, acute cholecystitis, non-functioning gall bladder, obstructive jaundice or common duct stones. 6. After appropriate diet and catharsis, 1 g of neomycin plus 1 g of erythromycin at 1 PM, 2 PM and 11 PM or 2 g of neomycin plus 2 g of metronidazole at 7 PM and 11 PM the day before an 8 AM operation. 7. For patients allergic to cephalosporins, clindamycin with either gentamicin, ciprofloxacin, levofloxacin (750 mg) or aztreonam is a reasonable alternative.

Treatment Guidelines from The Medical Letter • Vol. 2 ( Issue 20) • April 2004 28

Antimicrobial Prophylaxis for Surgery CHOICE OF DRUG FOR PREVENTION OF SURGICAL SITE INFECTION Nature of operation Head and Neck Surgery Incisions through oral or pharyngeal mucosa

Common pathogens

Neurosurgery

S. aureus, S. epidermidis

Ophthalmic

S. epidermidis, S. aureus, streptococci, enteric gramnegative bacilli, Pseudomonas

Anaerobes, enteric gramnegative bacilli, S. aureus

Recommended drugs

Adult dosage before surgery1

clindamycin + gentamicin OR cefazolin cefazolin OR vancomycin3

600-900 mg IV 1.5 mg/kg IV 1-2 grams IV 1-2 grams IV 1 gram IV

gentamicin, tobramycin, ciprofloxacin, gatifloxacin levofloxacin, moxifloxacin, ofloxacin or neomycingramicidin-polymyxin B cefazolin

multiple drops topically over 2 to 24 hours 100 mg subconjunctivally

Orthopedic

S. aureus, S. epidermidis

cefazolin12 OR vancomycin3,12

1-2 grams IV 1 gram IV

Thoracic (Non-Cardiac)

S. aureus, S. epidermidis, streptococci, enteric gramnegative bacilli

cefazolin or cefuroxime OR vancomycin3

1-2 grams IV 1.5 grams IV 1 gram IV

S. aureus, S. epidermidis, enteric gram-negative bacilli

cefazolin OR vancomycin3

1-2 grams IV 1 gram IV

S. aureus, S. epidermidis, cefazolin enteric gram-negative bacilli, OR vancomycin3 clostridia

1-2 grams IV 1 gram IV

Vascular Arterial surgery involving a prosthesis, the abdominal aorta, or a groin incision Lower extremity amputation for ischemia

8. Therapy is often continued for about five days. Ruptured viscus in postoperative setting (dehiscence) requires antibacterials to include coverage of nosocomial pathogens. 9. Urine culture positive or unavailable, preoperative catheter, transrectal prostatic biopsy, placement of prosthetic material. 10. Patients with previous pelvic inflammatory disease, previous gonorrhea or multiple sex partners. 11. Divided into 100 mg one hour before the abortion and 200 mg one half hour after. 12. If a tourniquet is to be used in the procedure, the entire dose of antibiotic must be infused prior to its inflation.

includes organisms rarely encountered in elective surgery, and their widespread use for prophylaxis would promote emergence of resistance.

serum and tissue levels of the drugs; there is no consensus on whether the infusion must be completed by the time of incision. For procedures lasting less than 4 hours, Medical Letter consultants recommend a single intravenous dose of an antimicrobial started within 60 minutes before the initial skin incision, which should provide adequate tissue concentrations throughout the procedure. If vancomycin or a fluoroquinolone is used, the infusion should begin 60-120 minutes before the incision is made in order to minimize the risk of antibiotic-associated reactions around the time of anesthesia induction and ensure adequate tissue levels of the drug at the time of incision.

PENICILLIN ALLERGY Cefazolin is often used for prophylaxis in penicillinallergic patients, but such patients rarely may have allergic reactions to cephalosporins. When allergy prevents use of a cephalosporin, vancomycin or clindamycin can be used, but neither is effective against gram-negative bacteria, so some Medical Letter consultants would add gentamicin (Garamycin, and others), ciprofloxacin (Cipro, and others), levofloxacin (Levaquin, 750 mg once) or aztreonam (Azactam), particularly for colorectal procedures, hysterectomies, and vascular surgery involving groin incisions.

Additional Doses – If the procedure is prolonged (>4 hours), major blood loss occurs, or an antimicrobial with a short half-life is used, redosing every 1-2 halflives of the drug should provide adequate antimicrobial concentrations during the procedure (cefazolin q25 hours, cefuroxime q3-4 hours, cefoxitin q2-3 hours, cefotetan and clindamycin q3-6 hours, and van-

TIMING AND NUMBER OF DOSES It has been common practice to give antibiotics at the time of anesthesia induction, which results in adequate

Treatment Guidelines from The Medical Letter • Vol. 2 ( Issue 20) • April 2004 29

Antimicrobial Prophylaxis for Surgery comycin q6-12 hours). Published studies of antimicrobial prophylaxis often use one or two doses postoperatively in addition to one dose just before surgery. Most Medical Letter consultants believe, however, that postoperative doses are unnecessary after wound closure and increase the risk of antimicrobial resistance.

57:633). Prophylactic antibiotics are generally not necessary for low-risk patients undergoing elective laparoscopic cholecystectomy (M Koc et al, Surg Endosc 2003; 17:1716; KJ Dobay et al, Am Surg 1999; 65:226; A Higgins et al, Arch Surg 1999; 134:611). Preoperative antibiotics can decrease the incidence of infection after colorectal surgery; for elective operations, an oral regimen of neomycin (not available in Canada) plus either erythromycin or metronidazole appears to be as effective as parenteral drugs. Many surgeons in the US use a combination of oral and parenteral agents (O Zmora et al, Dis Colon Rectum 2001; 44:1537). It is controversial whether the combination is more effective than either alone (RT Lewis, Can J Surg 2002; 45:173). Preoperative antimicrobials can decrease the incidence of infection after surgery for acute appendicitis (BR Andersen et al, Cochrane Database Syst Rev 2003; 2:CD001439).

CARDIAC Prophylactic antibiotics can decrease the incidence of infection after cardiac surgery, and intraoperative redosing has been associated with a decreased risk of postoperative infection in procedures lasting >400 minutes (G Zanetti et al, Emerg Infect Dis 2001; 7:828). Antimicrobial prophylaxis for prevention of device-related infections has not been rigorously studied. It is, however, generally given before placement of electrophysiologic devices, ventricular assist devices, ventriculoatrial shunts and arterial patches (LM Baddour et al, Circulation 2003; 108:2015). A meta-analysis of seven randomized studies of antimicrobial prophylaxis for implantation of permanent pacemakers showed a statistically significant reduction in the incidence of wound infection, inflammation or skin erosion (A DaCosta et al, Circulation 1998; 97:1796).

If perforation has occurred, antibiotics are often used therapeutically rather than prophylactically and are continued for 5-7 days. In studies of penetrating abdominal and intestinal injuries, however, a short course (12-24 hours) was as effective as 5 days of therapy (EP Dellinger et al, Arch Surg 1986; 121:23; A Bozorgzadeh et al, Am J Surg 1999; 177:125; EE Cornwell 3rd et al, J Gastrointest Surg 1999; 3:648).

GASTROINTESTINAL Antibiotic prophylaxis is recommended for esophageal surgery in the presence of obstruction, which increases the risk of infection. After gastroduodenal surgery the risk of infection is high when gastric acidity and gastrointestinal motility are diminished by obstruction, hemorrhage, gastric ulcer or malignancy, or by therapy with an H2-blocker such as ranitidine (Zantac, and others) or a proton pump inhibitor such as omeprazole (Prilosec, and others), and is also high in patients with morbid obesity (AJ Chong and EP Dellinger, Curr Treat Options Infect Dis 2003; 5:387). A dose of cefazolin before surgery can decrease the incidence of postoperative infection in these circumstances. Prophylactic antibiotics are not indicated for routine gastroesophageal endoscopy, but most clinicians use them before placement of a percutaneous gastrostomy (WK Hirota et al, Gastrointest Endosc 2003; 58:475; I Ahmad et al, Aliment Pharmacol Ther 2003; 18:209).

GENITOURINARY Medical Letter consultants do not recommend antimicrobials before most urological operations in patients with sterile urine. When the urine culture is positive or unavailable, or the patient has a preoperative urinary catheter, patients should be treated to sterilize the urine before surgery or receive a single preoperative dose of an appropriate agent. A meta-analysis that included 4260 patients with sterile preoperative urine undergoing transurethral prostatectomy concluded that antimicrobial prophylaxis decreased the incidence of postoperative bacteriuria and septicemia (A Berry and A Barratt, J Urol 2002; 167:571). Prophylaxis is recommended before transrectal prostatic biopsies because urosepsis has occurred (M Aron et al, BJU Int 2000; 85:682). Surgical prophylaxis is generally used if a urologic prosthesis (penile implant, artificial sphincter, synthetic pubovaginal sling, bone anchors for pelvic floor reconstruction) will be placed (A Gomelsky and RR Dmochowski, Curr Pharm Des 2003; 9:989).

Antimicrobials are recommended before biliary tract surgery for patients with a high risk of infection — those more than 70 years old and those with acute cholecystitis, a non-functioning gallbladder, obstructive jaundice or common duct stones. Many clinicians follow similar guidelines for antibiotic prophylaxis of endoscopic retrograde cholangiopancreatography (ERCP) (JS Mallery et al, Gastrointest Endosc 2003;

GYNECOLOGIC AND OBSTETRIC Antimicrobial prophylaxis decreases the incidence of infection after vaginal and abdominal hysterectomy

Treatment Guidelines from The Medical Letter • Vol. 2 ( Issue 20) • April 2004 30

Antimicrobial Prophylaxis for Surgery tion (DV Leaming, J Cataract Refract Surg 2003; 29:1412). There is no consensus supporting a particular choice, route or duration of antimicrobial prophylaxis (TJ Liesegang, Cornea 1999; 18:383). Preoperative povidone-iodine applied to the skin and conjunctiva has been associated with a lower incidence of culture-proven endophthalmitis (TA Ciulla et al, Ophthalmology 2002; 109:13). There is no evidence that prophylactic antibiotics are needed for procedures that do not invade the globe.

(C Chongsomchai et al, J Hosp Infect 2002; 52:302; AA Kamat et al, Infect Dis Obstet Gynecol 2000; 8:230). Prophylaxis is also used for laparoscopic hysterectomies. Antimicrobials, usually given after cord clamping, can prevent infection after elective and non-elective cesarean sections (F Smaill and GJ Hofmeyr, Cochrane Database Syst Rev 2002; 3:CD000933; D Chelmow et al, Am J Obstet Gynecol 2001; 184:656; L French, Curr Womens Health Rep 2003; 3:274). Antimicrobial prophylaxis can also prevent infection after first- and second-trimester elective abortion. One meta-analysis found a protective effect of perioperative antibacterials in all women undergoing induced abortions (GF Sawaya et al, Obstet Gynecol 1996; 87:884).

ORTHOPEDIC

Prophylaxis with antimicrobials has decreased the incidence of surgical site infection after head and neck operations that involve an incision through the oral or pharyngeal mucosa. One study in 74 patients undergoing surgery for head and neck cancer who received clindamycin beginning immediately preoperatively found no difference in infectious complications between continuing the drug for 24 hours (3 doses) or 5 days (15 doses); unfortunately, there was no singledose group (WR Carroll et al, Arch Otolaryngol Head Neck Surg 2003; 129:771).

Prophylactic antistaphylococcal drugs administered preoperatively can decrease the incidence of both early and late infection following joint replacement. They also decrease the rate of infection in compound or open fractures and when hip and other fractures are treated with internal fixation by nails, plates, screws or wires. If a proximal tourniquet is used for the procedure, the antibiotic infusion must be completed prior to its inflation. One large randomized trial found a single dose of a cephalosporin more effective than placebo in preventing wound infection after surgical repair of closed fractures (H Boxma et al, Lancet 1996; 347:1133). A prospective randomized study in patients undergoing diagnostic and operative arthroscopic surgery concluded that antibiotic prophylaxis is not indicated (JA Wieck et al, Orthopedics 1997; 20:133).

NEUROSURGERY

THORACIC (NON-CARDIAC)

An antistaphylococcal antibiotic can decrease the incidence of infection after craniotomy. In spinal surgery, the infection rate after conventional lumbar discectomy is low, but the serious consequences of surgical site infection have led many neurosurgeons to use perioperative antibiotics. A meta-analysis concluded that antibiotic prophylaxis is beneficial in preventing infection even in low-risk spinal surgery (FG Barker II, Neurosurgery 2002; 51:391). Infection rates are higher after prolonged spinal surgery or spinal procedures involving fusion or insertion of foreign material, and prophylactic antibiotics are often used (JB Dimick et al, Spine 2000; 25:2544). Studies of antimicrobial prophylaxis for implantation of permanent cerebrospinal fluid shunts have produced conflicting results.

Antibiotic prophylaxis is given routinely in thoracic surgery, but supporting data are sparse. In one study, a single preoperative dose of cefazolin before pulmonary resection led to a decrease in the incidence of surgical site infection, but not of pneumonia or empyema (R Aznar et al, Eur J Cardiothorac Surg 1991; 5:515). Other trials have found that multiple doses of a cephalosporin can prevent infection after closed-tube thoracostomy for chest trauma with hemo- or pneumothorax (RP Gonzalez and MR Holevar, Am Surg 1998; 64:617). Insertion of chest tubes for other indications, such as spontaneous pneumothorax, does not require antimicrobial prophylaxis.

OPHTHALMIC

Preoperative administration of a cephalosporin decreases the incidence of postoperative surgical site infection after arterial reconstructive surgery on the abdominal aorta, vascular operations on the leg that include a groin incision, and amputation of the lower extremity for ischemia. Many experts also recommend prophylaxis for implantation of any vascular prosthetic material, such as grafts for vascular access in hemodialysis.

HEAD AND NECK

VASCULAR

Data are limited on the effectiveness of antimicrobial prophylaxis for ophthalmic surgery, but postoperative endophthalmitis can be devastating. Most ophthalmologists use antimicrobial eye drops for prophylaxis, and some also give a subconjunctival injection or add antimicrobial drops to the intraocular irrigation solu-

Treatment Guidelines from The Medical Letter • Vol. 2 ( Issue 20) • April 2004 31

Antimicrobial Prophylaxis for Surgery Prophylaxis is not indicated for carotid endarterectomy or brachial artery repair without prosthetic material.

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Not indicated – Antimicrobial prophylaxis is generally not indicated for cardiac catheterization, varicose vein surgery, most dermatologic and plastic surgery, arterial puncture, thoracentesis, paracentesis, repair of simple lacerations, outpatient treatment of burns, dental extractions or root canal therapy because the incidence of surgical site infections is low. A study in patients undergoing cosmetic procedures who did not receive prophylactic antibiotics found that infection was more common after longer operations; the authors concluded that a single dose of cefazolin might be helpful before operations that last more than 3 hours (CA Fatica et al, Plast Reconstr Surg 2002; 109:2570).

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Controversial – The need for prophylaxis in breast surgery, herniorraphy and other "clean" surgical procedures has been controversial (R Knight et al, Am J Surg 2001; 182:682; DF D’Amico et al, J Chemother 2001; 13 spec No 1:108). Medical Letter consultants generally do not recommend surgical prophylaxis for these procedures unless prosthetic material (synthetic mesh, saline implants, tissue expanders) will be placed, because of the low rate of infection, the low morbidity of these infections and the potential adverse effects of using prophylaxis in such a large number of patients.

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Treatment Guidelines from The Medical Letter • Vol. 2 ( Issue 20) • April 2004 32