Antibiotic prophylaxis

Holzheimer RG.

Epidemiology

Approximately 1 million patients suffer from wound infections each year in the United States. Wound infections are responsible for extension of hospital stay on an average of 1 week and for increase in hospital costs by 20% (1).

Pathogenesis

The development of wound infection requires a local inoculum which is sufficient to overcome the local host defense. The development of wound infection depends on microbial virulence factors, the local environment, systemic factors, e.g., comorbidity, and surgical technique. Antibiotic prophylaxis plays an important part in prevention of wound infections. The efficacy of antibiotic prophylaxis has been demonstrated to be significant; however, antibiotic prophylaxis cannot be a substitute for any other preventive measure (2). The scientific basis for the perioperative use of antibiotics was established by Burke (3).Polk and Stone have confirmed the hypothesis in clinical studies and laid the ground for antibiotic prophylaxis in surgery.(4,5)

Classification and Risk factors

It has been demonstrated in large clinical studies that the classification of operative wounds, e.g., clean, clean-contaminated, contaminated, and dirty, is associated with a different risk for the occurence of wound infections (6). (Table I) The classification of postoperative wounds is based on a definition of the National Academy of Sciences, National Research Council (NRC), Division of Medicine, Ad Hoc Committee on Trauma (7). The risk of wound infections in trauma patients is considered to be similar to equivalent classes of elective operations (8). There is a widely accepted agreement that antibiotic prophylaxis in clean-contaminated, contaminated and dirty wounds is warranted.

Table I. Classification of operative wounds and risk of infection.

Table I

Classification of operative wounds and risk of infection.

Controversy exists about the necessity of antibiotic prophylaxis in clean operations. The argument against the prophylaxis is the low wound infection rate of 2% and less. However, it is well recognized that 40% of wound infections occur after clean operations (9). and in some clean operations the effect of wound infection may be devastating for the patient. We have observed in clean operation, e.g. hyperthermic perfusion of melanoma patients, an infection rate of 13% which was mainly due to a prolonged operation time and the use of immunosupressive agents (10). There is evidence that the infection rate in clean operations may be reduced by antibiotic prophylaxis by 17%. (11)

Risk factors associated with increased risk of infection may be systemic or local factors. Systemic factors include diabetes, corticosteroid use, obesity, age, malnutrition, recent surgery, massive transfusion, comorbidity (more than three diagnoses), and American Society of Anaesthesiologists (ASA) class 3, 4 or 5. Local factors are considered to be foreign body, electrocautery, injection with epinephrine, wound drains, hair removal with razor, previous irradion. Remote infection, the length of operation (> 2 hours), and three comorbid diagnoses were identified to be independent risk factors (12,13). However, meticulous surgical technique remains the mainstay of infection control. (14)

Selection of antibiotics

Antibiotics used for prophylaxis should be active against the most likely infecting organism with relevant tissue penetration. Antibiotics may be applied topical, systemical or enteral. They should show a low toxicity, a low incidence of allergy, and should be involved in the selection of virulent organisms.

The antibiotic should be administered ideally 30 minutes before incision in order to achieve relevant tissue concentration. In operations lasting longer than three hours a second dosage is recommended. There is no evidence to support a prolongation of antibiotic administration to 24 or 48 hours in most instances. Single dose is cheaper and does not increase the risk of the developement of bacterial resistance. (1517)

The most commonly administered drug in the United States is cefazolin (Ancef, Kefzol) (18). Gram-negative and anaerobic pathogens are likely to influence wound infections in operations of the alimentary tract or the hepatobiliary system and should be covered by antibiotic prophylaxis. Cefotetan, cefoxitin, ceftizoxime with or without metronidazole are possible options in these operations. Quinolones have been mentioned by some authors; however, there is no evidence to support the use of these compounds in antibiotic prophylaxis.

Recommendation for specific procedures (Table II)

  • Cutaneous and soft tissue procedures
    There is no general recommendation for antibiotic prophylaxis in soft tissue or cutaneous procedures available.
  • Head and neck procedures
    In case of operations of the esophagus antibiotic prophylaxis is recommended (19). Cefazolin is commonly used. (20)
  • General thoracic procedures
    Antibiotic prophylaxis is routinely used in most institutions, preferably with cefazolin. The evidence is based mostly on studies of pulmonary resection for lung cancer (2124). The rationale for antibiotic prophylaxis in thoracic procedures is not yet clear.
  • Gastrointestinal tract procedures
    Prophylaxis is recommended for most operations in the gastrointestinal tract. The increasing number of pathogens in the lower gastrointestinal tract is a strong argument for antibiotic coverage. However, despite low microbial count in the stomach, duodenum or small bowel, antibiotic prophylaxis may be indicated when there is a situation with decreased gastric acidity, previous use of antacids, histamine blockers or proton pump inhibitors, stasis, upper gastrointestinal bleeding, morbid obesity or advanced malignancy. The levels of intragastric flora were increased in patients in whom gastric pH was increased or gastric motility impaired. These patients had postoperative infection rates of greater than 20% (25). Several studies have confirmed that antibiotic prophylaxis in high risk patients may reduce the infection rate from 35% to 0–5% (2628). Cefazolin may be recommended for operations of the upper gastrointestinal tract which is associated with one of the afore mentioned factors.
    In colorectal operation there is an increased risk of wound infection due to the large number of pathogens. It has been demonstrated that antibiotic prophylaxis covering gram-negative aerobes and anaerobic bacteria may reduce the incidence of wound infections from 50% to less than 9% (2931). Antibiotic prophylaxis may be given either orally or parentally. However, preoperative mechanical bowel preparation with purgatives, e.g., polyethylene glycol, mannitol or magnesium citrate, and enemas are a cornerstone of the infection prophylaxis. In general, the addition of oral antibiotics may reduce the risk of infection to approximately 9% which is similar to the risk of infection when parenteral antibiotics are given alone. (32)
    In the United States it is common practice to use both oral and parenteral antibiotic prophylaxis (33). For intraluminal prophylaxis erythromycin base or metronidazole and neomycin or kanamycin (3 times 1g per dose per day) are given the day before the operation. Second generation cephalosporins, e.g., cefotetan and cefoxitin, are administered parenterally 30 minutes before incision.
    In appendectomy cefotetan or cefoxitin may be the antibiotic of choice for prophylaxis. Single dose is equally effective as multiple doses (34). In combined topical and systemic antibiotic prophylaxis the wound infection rate was reduced to 5% which is equal to wound infection rate after systemic antibiotic prophylaxis. The use of topical povidone-iodine alone is not recommended (35). Preincisional or intraincisional administration of metronidazole was able to reduce the wound infection rate (36). Single dose cefamandole is as effective as cefamandole plus carbenicillin to reduce the rate of wound infections (37). Bauer et al. were able to show a significant reduction in wound infections after normal appendectomy, acutely inflammed appendix and gangrenous appendix by cefoxtin antibiotic prophylaxis (38). Lau et al. have studied the effect of bacteriology on septic complications in appendicitis. The most effective agent against anaerobes was metronidazole, the most effective agent against aerobes aminoglycosides and cephalosporins. Moxalactam was considered to be the best single agent against aerobes and anaerobes. (39)
    Some authors accept metronidazole combined with an aminoglycoside or a quinolone for prophylaxis. In a recent systematic review of randomised controlled trials for antimicrobial prophylaxis in colorectal surgery it was again confirmed that prophylactic antibiotics reduce the wound infection rate, however it was impossible to say which antibiotic is the best. Certain regimens appear to be inadequate, e.g., metronidazole alone, doxycycline alone, piperacillin alone, oral neomycin plus erythromycin alone). There is no convincing evidence that new-generation cephalosporins are more effective than first-generation cephalosporins. The authors found infection rates for the same antibiotic to be as low as 2% and as high as 30% (40). There is evidence that bowel prep, decontamination by oral nonabsorbable antibiotics and systemic antibiotic prophylaxis covering aerobic and anaerobic pathogens is the best regimen for prevention of wound infections. Most studies favour prophylaxis in appendectomy and gastroduodenal surgery when bacterial growth may be likely (Grade A/B).
  • Biliary tract procedures
    Antibiotic prophylaxis for biliary tract operations is considered optional by some authors and depends largely on the identification of risk factors, e.g., advanced age, common duct disease, cholecystitis, jaundice, previous biliary tract surgery. Cefazolin is accepted as effective antibiotic prophylaxis. The addition of mezlocillin may be useful in selected cases (4144). The clinical success rate in the 1g cefotetan, 2g cefotetan and 2g cefoxitin group was 97%, 98% and 97%, respectively (45). Topical cefamandole achieved similar results as systemic antibiotic prophylaxis. The authors concluded that the application of topical cefamandole is sufficient prophylaxis in biliary surgery (46). In a comparison of 1g cefotaxime to 4 doses of 2g cefoxitin cefotaxime was superior to cefoxitin (47). Hjortrup et al. found no difference in wound infection rate after single dose ceftriaxone and 2 doses of cefuroxime. (48) The wound infection rate after cefazolin and ceftizoxime in elective biliary surgery was comparable (7% versus 8%) (49,50) Kellum et al. found no difference in clinical success between first generation cephalosporins and third generation cephalosporins (51).One dose of ceftriaxone achieved similar results than one perioperative and three postoperative doses of cefazolin (52). Cefamandole and ampicillin prophylaxis achieved similar results in biliary surgery (wound infection rate 1.8% and 3.2%, respectively) (53,54). Sarr et al. compared systemic and topical antibiotic regimens. There was no difference in the wound infection rate when topical antibiotics were given alone, combined with cefoxtin or combined with penicillin, tobramycin and clindamycin (55). In a meta-analysis Meijer et al. compared all available clinical trials from 1965 to 1988. Wound infection rates in controls ranged from 3% to 47%. The overall difference in infection rate was 9% in favour of antibiotic prophylaxis (95% CI 7–11%). There was no difference between first and third generation cephalosporins nor single versus multiple doses (56). There is evidence that antibiotic prophylaxis in biliary surgery reduces the wound infection rate. In general, the administration of systemic antibiotics is acepted. (Grade A/B)
  • Vascular procedures
    Antibiotic prophylaxis is recommended in incisions of the groin, in procedures using synthetic material, and in procedures affecting the aorta. Cefazolin is the appropriate antibiotic as in most instances S. aureus and S. epidermidis are isolated (57). Single-shot may be accepted although there is evidence that two doses may be superior. There was no difference detected in patients who received topical (incisional) cephradine, systemic cephradine or both (58). Hasselgren et al. have compared the effect of cefuroxime 1.5g every 8 hours at the day of operation, three days versus placebo and found a reduction in wound infection rate from 16.7% in the placebo group to 3.8% in the day 1 only group and 4.3% in the three day group (59). Controversy exists whether multiple-dose antibiotic prophylaxis produces better results. Hall et al. have shown that multiple-dose regimen with ticarcillin 3.0g/clavulanate 0.1g (Timentin) was superior to single dose (60). In a retrospective review of a randomized trial of two antibiotics (cephalothin sodium versus oxacillin sodium) there was no difference in wound infection rate (61). In summary, there is evidence that antibiotic prophylaxis in vascular surgery is relevant for the reduction in wound infection. It is not yet decided that multiple dose of antibiotics are superior to single dose. (Grade A/B)
  • Breast and hernia procedures
    It has been demonstrated in several studies that antibiotic prophylaxis in groin or breast surgery may lead to a reduction in wound infection despite the intrinsically low risk. The application of synthetic mesh in hernia surgery may be alleviated by the administration of prophylactic antibiotics (6264). The efect of antibiotic prophylaxis may not be visible in other clean operations. A reduction of complications was seen only in axillary lymph node dissection whereas after inguinal lymph node dissection the complication rate was 69% in the antibiotic group and 62% in the placebo group. (65)
  • Laparoscopic procedures
    The role of antibiotic prophylaxis in laparoscopic procedures needs to be determined. In a retrospective study incisional infections were discovered in 11 of 556 cases, of whom 10 had received prophylactic antibiotics. In a prospective randomized study in 53 patients no incisional infection was discovered (66). In 150 patients undergoing elective laparoscopic cholecystectomy there was no difference in the infection rate in the cefotetan group, the cefazolin group and the intravenous placebo group. The overall infection rate was 2.4% (67). Cefotaxime was given randomly as antibiotic prophylaxis.The wound infection rate in the treatment group was 7%, in the placebo group 10% (not significant) (68). In a prospective open study in 253 patients cefuroxime was administered as antibiotic prophylaxis; 2 of 253 patients suffered from wound infection.69 In summary, there is no evidence to support the antibiotic prophylaxis in laparoscopic cholecystectomy (Grade A/B).
  • Trauma surgery
    In trauma patients a major problem is the morbidity due to infections. Single-antibiotic use may suffice for prophylaxis in penetrating abdominal trauma (7072). 12 hours of antibiotic prophylaxis were comparable to fiveday antibiotic treatment in the prevention of postoperative infections (73). The decision for short term prophylaxis may depend on the operative findings, e.g., colonic injury (74). There is an increased risk when the following factors are present: injury to the liver, pancreas, or colon; abdominal trauma index > 25, and/or prolonged surgery (75). A revised Trauma Index value above 20 and a colon injury represent an increased risk for intra-abdominal infection (76). Griswold et al. compared the efficacy of three different antibiotics (cefoxitin, ceftizoxime, mezlocillin) in patients with a trauma index of 8.8 and an infection rate of 10.3% to patients with a trauma index of 28.2 and an infection rate of 42.3%. Only in patients with ceftizoxime there was no increase in the infection rate observed (77). Cefoxitin prophylaxis is as safe and effective in preventing infections as a triple drug treatment. The overall infection rate was 14.5% in the cefoxitin treated patients versus 18.0% in the triple drug treated patients (78). Cefoxitin is as effective as clindamycin/tobramycin and superior to cefamandole (79). However, an improved coverage of enterococcal and Bacteroides by ampicillin/sulbactam may lower the abdominal surgical wound infection rate when compared to cefoxitin (80). Harlan Stone has demonstrated the efficacy of antibiotic prophylaxis to reduce infections in closed tube thoracostomy (81). The incidence of posttraumatic empyema ranges between 0 and 18%. Administration of antibiotics for longer than 24 hours did not reduce the risk compared with a shorter duration (82). A clear management guideline for prophylactic use in penetrating abdominal trauma was rececently published by the AAST.Single preoperative dose of antibiotics with coverage of aerobic and anaerobic pathogens is the standard for treating trauma patients with penetrating abdominal trauma. In the presence of injury to hollow viscus a continuation of antibiotics is recommended for 24 hours only. Aminoglycosides have suboptimal activity in patients with serious injury and should not be used (83). The use of cephalosporins may avoid serious side effects (84). (Grade A and B)

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