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Chapter: Basic & Clinical Pharmacology - Clinical Use of Antimicrobial Agents

Antimicrobial Prophylaxis

Antimicrobial agents are effective in preventing infections in many settings.


Antimicrobial agents are effective in preventing infections in many settings. Antimicrobial prophylaxis should be used in circum-stances in which efficacy has been demonstrated and benefits outweigh the risks of prophylaxis. Antimicrobial prophylaxis may be divided into surgical prophylaxis and nonsurgical prophylaxis.

Surgical Prophylaxis

Surgical wound infections are a major category of nosocomial infections. The estimated annual cost of surgical wound infections in the United States is $1.5 billion.

The National Research Council (NRC) Wound Classification Criteria have served as the basis for recommending antimicrobial prophylaxis. NRC criteria consist of four classes [see Box: National Research Council (NRC) Wound Classification Criteria].

The Study of the Efficacy of Nosocomial Infection Control (SENIC) identified four independent risk factors for postopera-tive wound infections: operations on the abdomen, operations lasting more than 2 hours, contaminated or dirty wound classifi-cation, and at least three medical diagnoses. Patients with at least two SENIC risk factors who undergo clean surgical procedures have an increased risk of developing surgical wound infections and should receive antimicrobial prophylaxis.

Surgical procedures that necessitate the use of antimicrobial prophylaxis include contaminated and clean-contaminated opera-tions, selected operations in which postoperative infection may be catastrophic such as open heart surgery, clean procedures that involve placement of prosthetic materials, and any procedure in an immunocompromised host. The operation should carry a signifi-cant risk of postoperative site infection or cause significant bacte-rial contamination.

General principles of antimicrobial surgical prophylaxis include the following:

1. Theantibiotic should be active against common surgical wound pathogens; unnecessarily broad coverage should be avoided.

2. The antibiotic should have proved efficacy in clinical trials.

3. The antibiotic must achieve concentrations greater than the MIC of suspected pathogens, and these concentrations must be present at the time of incision.

4. The shortest possible course—ideally a single dose—of the most effective and least toxic antibiotic should be used.

5. The newer broad-spectrum antibiotics should be reserved for therapy of resistant infections. If all other factors are equal, the least expensive agent should be used.

The proper selection and administration of antimicrobial pro-phylaxis are of utmost importance. Common indications for sur-gical prophylaxis are shown in Table 51–7. Cefazolin is the prophylactic agent of choice for head and neck, gastroduodenal, biliary tract, gynecologic, and clean procedures. Local wound infection patterns should be considered when selecting antimicro-bial prophylaxis. The selection of vancomycin over cefazolin may be necessary in hospitals with high rates of methicillin-resistant Saureus or S epidermidis infections. The antibiotic should be presentin adequate concentrations at the operative site before incision and throughout the procedure; initial dosing is dependent on the volume of distribution, peak levels, clearance, protein binding, and bioavailability. Parenteral agents should be administered dur-ing the interval beginning 60 minutes before incision; administra-tion up to the time of incision is preferred. In cesarean section, the antibiotic is administered after umbilical cord clamping. If short-acting agents such as cefoxitin are used, doses should be repeated if the procedure exceeds 3–4 hours in duration. Single-dose pro-phylaxis is effective for most procedures and results in decreased toxicity and antimicrobial resistance.Improper administration of antimicrobial prophylaxis leads to excessive surgical wound infection rates. Common errors in anti-biotic prophylaxis include selection of the wrong antibiotic, administering the first dose too early or too late, failure to repeat doses during prolonged procedures, excessive duration of prophy-laxis, and inappropriate use of broad-spectrum antibiotics.

National Research Council (NRC) Wound Classification Criteria

Clean: Elective, primarily closed procedure; respiratory, gas-trointestinal, biliary, genitourinary, or oropharyngeal tract not entered; no acute inflammation and no break in technique; expected infection rate 2%.

Clean contaminated: Urgent or emergency case that is oth-erwise clean; elective, controlled opening of respiratory, gas-trointestinal, biliary, or oropharyngeal tract; minimal spillage or minor break in technique; expected infection rate 10%.

Contaminated: Acute nonpurulent inflammation; majortechnique break or major spill from hollow organ; penetrat-ing trauma less than 4 hours old; chronic open wounds to be grafted or covered; expected infection rate about 20%.

Dirty: Purulence or abscess; preoperative perforation ofrespiratory, gastrointestinal, biliary, or oropharyngeal tract; penetrating trauma more than 4 hours old; expected infec-tion rate about 40%.

Nonsurgical Prophylaxis

Nonsurgical prophylaxis includes the administration of antimicro-bials to prevent colonization or asymptomatic infection as well as the administration of drugs following colonization by or inocula-tion of pathogens but before the development of disease. Nonsurgical prophylaxis is indicated in individuals who are at high risk for temporary exposure to selected virulent pathogens and in patients who are at increased risk for developing infection because of under-lying disease (eg, immunocompromised hosts). Prophylaxis is most effective when directed against organisms that are predictably sus-ceptible to antimicrobial agents. Common indications and drugs for nonsurgical prophylaxis are listed in Table 51–8.

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