Preoperative antibiotic prophylaxis is defined as the administration of antibiotics prior to performing surgery to help decrease the risk of postoperative infections. The evidence supporting routine preoperative use of antibiotic prophylactic administration continues to grow, with a 2008 study highlighting the effectiveness of its administration during total hip and knee replacement, reducing the absolute risk of wound infection by over 80% compared to patients treated with no prophylaxis.[1] The routine administration of prophylactic antibiotics is standard in cases in which a patient will have an artificial implant or foreign body implanted as part of the procedure, in bone grafting procedures, and other surgeries in which large dissections and higher amounts of anticipated blood loss is expected.

The timing of antibiotic administration may vary, but the goal of administering preoperative systemic prophylactic antibiotics is to have the concentration in the tissues at its highest at the start and during surgery.[2][3] The literature supports at least 30 minutes, but no greater than 60 minutes before the skin incision is made as to the optimal timing for the pre-operative administration of most commonly used antibiotics.[4][5][2] Special consideration is given for ideal preoperative timing when using a tourniquet, as the administration is least effective when the antibiotic is given after the application of a tourniquet.[6]

The most common organisms implicated as causes of surgical site infections include[7]:

• staphylococcus aureus
• staphylococcus epidermidis
• aerobic streptococci
• anaerobic cocci

Other organisms, such a cutibacterium acnes is characteristically isolated in the setting of postoperative infections following shoulder surgery.

In general, the preoperative antibiotic selection is based on the anatomic region undergoing the specific surgical procedure.  The goal when determining appropriate antibiotic selection is to have achieved a relatively narrow spectrum of activity while ensuring the most common organisms are targeted. Additionally, preoperative antibiotics are chosen based on a multitude of factors including cost, safety, ease of administration, pharmacokinetic profile, bacteriocidal activity, and hospital resistance patterns. By addressing all of these factors during antibiotic selection, surgical site infections (SSIs) are minimized.  SSIs, in aggregate, constitute a significant factor driving negative patient-reported outcomes and independent risk factors for increasing financial burden to the entire healthcare system.[8]

Cefazolin is used most often for surgical prophylaxis in patients with no history of beta-lactam allergy, a history of MRSA infection, or when consideration is given to surgical sites in which the most probable organisms that are not covered by cefazolin alone (e.g., appendectomy, colorectal).

In patients requiring only cefazolin for preoperative surgical prophylaxis, clindamycin or vancomycin are often used as alternatives in those with significant beta-lactam allergies. In the case of MRSA colonization, or in select patients at high-risk for MRSA (i.e. patients residing in nursing homes, patients with a history of MRSA infection, or patients with current positive MRSA colonization testing) vancomycin is the alternative unless additional antibiotics are required for possible gram-negative or anaerobic organisms.[9] For patients requiring additional microbe coverage (e.g., colorectal), multiple options may be considered including cefazolin plus metronidazole, cefoxitin, or ertapenem. Additional antibiotics are options based on specific surgical sites in addition to hospital-specific and patient-specific antibiotic resistance.[10]

Weight-based dosing should be followed per standardized protocol, and administration should occur within 1 hour of skin incision and continue for 24 hours postoperatively. Furthermore, surgical durations of greater than 4 hours or estimated blood loss over 1,500 mL necessitates repeat intraoperative dosing of antibiotics.[11] Weight-based guidelines include the following[12]:

• Cefazolin: 2 g (3 g for weight >120 kg) —standard adult surgical prophylaxis guidelines
• Vancomycin: 15 mg/kg 

Wound classifications [13]

Wound types can be classified as clean, clean-contaminated, contaminated, or dirty/infected according to the Centers for Disease Control and Prevention's (CDC) National Healthcare Safety Network (NHSN). Clean wounds are not infected, without inflammation, primarily closed, and do not include the organ systems that are outlined in a clean-contaminated wound. Clean-contaminated wounds involve the respiratory, alimentary, genital, and urinary tract as long as the tract is entered without unusual contamination. Contaminated wounds include open, fresh accidental wounds including those with non-purulent inflammation. Contaminated wounds also include procedures with major breaks in sterile technique or gross spillage from the gastrointestinal tract. Dirty or infected wounds are old traumatic wounds with devitalized tissue or involve existing clinical infection or perforated viscera. During clean procedures, skin florae such as coagulase-negative staphylococci (e.g., Staphylococcus epidermidis or Staphylococcus aureus) are predominant pathogens in surgical site infections. In clean-contaminated procedures, the most commonly found organisms causing surgical site infections are skin flora, gram-negative rods, and Enterococci.[14]

Skin preparation 

Other preoperative actions include basic infection control strategies, instrument sterilization, and a patient's skin preparation (e.g., methicillin-resistant Staphylococcus aureus [MRSA] decolonization, appropriate hair removal, skin antiseptic)[15].  In regards to the latter, it is commonly recommended that patients about to undergo surgery perform a combination of a standard soap-and-water shower and chlorhexidine gluconate cloth wash prior to surgery. Murray et al. previously demonstrated that the combined protocol resulted in a 3-fold reduction in colony count for coagulase-negative Staphylococcus (CNS), a significant decrease in the rate of positive cultures for CNS and Corynebacterium, and a significant decrease in overall bacterial burden compared to soap-and-water shower alone.[16]

Screening for MRSA via swabs of the anterior nares weeks before elective arthroplasty procedures and reflexively treating patients based on culture results is generally institution dependent. Positive MRSA culture results can be treated with either 2% mupirocin twice daily for 5 days preoperatively to the nares or 5% povidone-iodine solution to each nostril for 10 seconds per nostril, 1 hour prior to surgery, in addition to vancomycin administration at the time of surgery.[17][18]

Splenectomized patients

Another area requiring special attention and consideration is in regard to infection prevention in patients with hyposplenism (or status post splenectomy). Davies et al. provided updated guidelines for the prevention and treatment of infections in patients with dysfunctional (or absent) splenic function:

• Pneumococcal immunization
• Haemophilus influenza type B vaccination
• Meningococcal group C conjugate vaccination
• Yearly influenza immunization
• Lifelong prophylactic antibiotics (oral phenoxymethylpenicillin or erythromycin)

Multiple antibiotic classes are recommended for use in preoperative antibiotic prophylaxis. The antibiotics utilized are bactericidal instead of bacteriostatic. This means that any of the targeted organisms are killed instead of just preventing the multiplication of further growth. It should be noted that certain antibiotics can exhibit bacteriostatic or bactericidal properties depending on bacterial sensitivity and antibiotic concentration. For example, clindamycin is bacteriostatic at lower doses, but at higher doses, it can exhibit bactericidal properties. In most surgeries, the intent is to ensure the bactericidal concentration has been reached in the blood and tissues before incision.

The majority of preoperative prophylactic antibiotics are administered intravenously (IV). The initial timing of administration, redosing if applicable, duration of prophylactic therapy, and dosing in obese patients are important components in the prevention of surgical site infections as well as antimicrobial stewardship.[19] Avoiding unnecessary use of antibiotics helps diminish the occurrence of adverse effects and antibiotic resistance development.  Antibiotics should be given within 30 to 60 minutes of a surgical incision. Exceptions include vancomycin and levofloxacin, which require administration within 120 minutes of the procedural incision due to longer administration times. If a patient is already receiving an antibiotic for another infection before surgery, and it is appropriate for surgical prophylaxis, an extra dose of the antibiotic can be administered within 60 minutes of the incision. If a patient is already receiving vancomycin and has renal failure, cefazolin should be considered before surgery instead of an extra dose of vancomycin.[20]

Redosing antibiotics is an important factor due to the half-life of the particular antibiotic used. Factors such as renal dysfunction and extensive burns may impact the half-life of an antibiotic. Based on the antibiotics mentioned above, cefazolin and cefoxitin would have to be administered more than once depending on the length of the procedure. A perioperative dose of cefazolin should be administered again at four hours after the initial preoperative dose while cefoxitin should be administered again two hours later. Redosing antibiotics due to significant blood loss or dilution during surgery are other considerations being studied at this time.

Unless there is a known infection, prophylactic antibiotics should be discontinued within 24 hours. There remains controversy regarding the duration of therapy to 48 hours postoperatively following cardiothoracic surgery. Two meta-analyses compared 24 hours versus 48 hours as the cut-off in cardiac surgeries and found a significant decrease in surgical site infections with the extended duration, particularly in sternal infections. The most recent guidelines from the CDC state that additional prophylactic antibiotics should not be administered after the surgical incision is closed in clean and clean-contaminated procedures. This recommendation applies to patients with or without a drain after the surgical site is closed, although there could be procedure-specific exceptions.

The three antibiotics used in adult surgical prophylaxis where weight-based dosing is recommended are cefazolin, vancomycin, and gentamicin. For patients receiving cefazolin, 2 g is the current recommended dose except for patients weighing greater than or equal to 120 kg, who should receive 3 g. There is some literature stating cefazolin 2 g  should be sufficient for a patient at any adult weight. Vancomycin is dosed at 15 mg/kg, and gentamicin is dosed 5 mg/kg. Other commonly used prophylactic antibiotics in adults are dosed as the following:  clindamycin 900 mg, cefoxitin 2 g, and ertapenem 1 g. All prophylactic antibiotics for pediatrics are dosed based on milligrams per kilogram body weight. Examples of pediatric dosages include the following: cefazolin 30 mg/kg and vancomycin 15 mg/kg.  Pediatric surgical prophylaxis dosages should not exceed the usual adult dose.

Limiting the duration of all antibiotics is important since any antimicrobial usage can alter hospital and patient bacterial flora, which can potentially lead to colonization, resistance, or Clostridium difficile. In addition, the judicious use of vancomycin must be considered in order to mitigate the potentially increased risk of vancomycin-resistant enterococcus (VRE).

Beta-lactam antibiotics, including cephalosporins, are commonly used for surgical prophylaxis, so it is important to identify when these antibiotics are contraindicated. If a patient has an immunoglobulin (IgE) mediated (i.e., type 1) allergy to penicillin, then penicillins, cephalosporins, and carbapenems should not be administered. A type 1 reaction would be considered anaphylaxis, urticaria, or bronchospasm that occurs 30 to 60 minutes following administration of the antibiotic. Cephalosporins and carbapenems are considered safe in patients who have not had a type-1 reaction or exfoliative dermatitis (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis). Obtaining a thorough allergy history from each patient is vital to ensure if the allergy stated by the patient is a real and significant allergy that would impact the usual preoperative surgical prophylaxis.