Continuing Education Activity

Preoperative antibiotic prophylaxis is administering antibiotics before performing surgery to help decrease the risk of postoperative infections. The evidence supporting routine preoperative use of prophylactic antibiotic administration continues to grow. 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, bone grafting procedures, and other surgeries with extensive dissections and expectations for higher amounts of anticipated blood loss. This activity will highlight the rationale, timing, agent selection, coverage, and monitoring pertinent for interprofessional team members involved in the administration of preoperative antibiotic prophylaxis to patients.

Objectives:

• Explain the rationale behind preoperative antibiotic prophylaxis.
• Summarize the evidence for the timing of administration with preoperative antibiotic prophylaxis.
• Review the follow-up monitoring necessary to determine the successful implementation of preoperative antibiotic prophylaxis.
• Outline interprofessional team strategies for improving care coordination and communication to advance preoperative antibiotic prophylaxis, where it is indicated and improves patient outcomes.

Indications

Preoperative antibiotic prophylaxis is defined as administering antibiotics prior to performing surgery to help decrease the risk of postoperative infections. The evidence supporting routine preoperative use of prophylactic antibiotic administration continues to grow. A 2008 study highlights 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 where a patient will have an artificial implant or foreign body implanted as part of the procedure, bone grafting procedures, and other surgeries with extensive dissections or expected high blood loss.

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 to the optimal timing for the preoperative administration of most commonly used antibiotics.[4][5][2] Special consideration is given to 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 as Cutibacterium acnes, are characteristically isolated in the setting of postoperative infections following shoulder surgery.

The preoperative antibiotic selection is generally based on the anatomic region undergoing the specific surgical procedure. When determining appropriate antibiotic selection, the goal 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 many 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. In aggregate, SSIs constitute a significant factor driving negative patient-reported outcomes and independent risk factors for increasing the 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 or of MRSA infection. It is not used for surgical sites in which the most probable organisms 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 for those with significant allergies to the medication. Most patients with a beta-lactam allergy are able to tolerate cefazolin. In the case of MRSA colonization, or 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] Multiple options may be considered for patients requiring additional microbe coverage (e.g., colorectal), 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 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 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 significant breaks in sterile technique or gross spillage from the gastrointestinal tract. Dirty or infected wounds are old traumatic wounds with devitalized tissue, 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] Regarding 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 before 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]

MRSA screening 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 five 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 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)

Mechanism of Action

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.

Administration

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 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 that agent 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 vancomycin dose.[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 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. They 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. Although there could be procedure-specific exceptions, this recommendation applies to patients with or without a drain after the surgical site is closed.

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. Some literature states that cefazolin 2 g  should be sufficient for a patient at any adult weight. Vancomycin is dosed at 15 mg/kg, and gentamicin is dosed at 5 mg/kg. Other commonly used prophylactic antibiotic dosing regimens in adults are clindamycin 900 mg, cefoxitin 2 g, and ertapenem 1 g. All prophylactic antibiotics for pediatrics are dosed based on milligrams per kilogram of body weight. Examples of pediatric dosages include cefazolin 30 mg/kg and vancomycin 15 mg/kg. Pediatric surgical prophylaxis dosages should not exceed the usual adult dose.

Adverse Effects

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. The judicious use of vancomycin must be considered to mitigate the potentially increased risk of vancomycin-resistant enterococcus (VRE).

Contraindications

Beta-lactam antibiotics, including cephalosporins, are commonly used for surgical prophylaxis, so it is crucial 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 determine whether the patient's allergy is a real and significant allergy that would impact the usual preoperative surgical prophylaxis. 

Monitoring

Surgical site infections may occur for various reasons, including, but not limited to, incorrect antibiotic usage. When considering antibiotic prophylaxis practices, the correct antibiotic dosage, timing of the initial dose, and timing of any applicable redosing are major factors to review to ensure best practices are always followed. If an institution recommends a specific antibiotic in surgery when additional antibiotics are options, monitoring should ensure no surgical site infections occur due to increasing local resistance. One example could be that growing clindamycin resistance has translated to increased surgical site infections in those receiving clindamycin due to a penicillin allergy. That information could lead an institution to switch to vancomycin instead of clindamycin in that patient population. Antibiotic selection should also be reviewed to avoid using antibiotics, resulting in new or worsening resistance patterns identified on the antibiogram. An institution may choose to use cefoxitin instead of ertapenem in colorectal surgeries to avoid excessive usage of the carbapenem class when applicable, especially if the institution has an escalating number of carbapenem-resistant organisms.[21]

Toxicity

No apparent toxicities are known with the recommended doses. This is partially due to the limited duration of antibiotic exposure in surgical prophylaxis.

Enhancing Healthcare Team Outcomes

The comprehensive and consistent practice regarding the routine perioperative antibiotic prophylactic measures requires the coordination of the entire perioperative interprofessional healthcare staff. This includes but is not limited to the entire operating room and perioperative staff members (including surgical techs, perioperative-based nursing staff, floor nurses, advanced practitioners, pharmacists, and all clinicians participating in the care of surgical patients). This interprofessional approach will optimize antibiotic prophylaxis, minimize adverse events, and drive optimal patient outcomes. [Level 5]