Preoperative Antibiotic Prophylaxis


Article Author:
Marsha Crader


Article Editor:
Matthew Varacallo


Editors In Chief:
William Gossman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
2/13/2019 7:22:52 AM

Indications

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 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: [0]

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

Other organisms, such a cutibacterium acnes (formerly known as propionibacterium 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[9]) vancomycin is the alternative unless additional antibiotics are required for possible gram-negative or anaerobic organisms. 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 [0].

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 duration 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 [0]

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 flora 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 [0].

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)[0].  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 re?exively treating patients based on culture results is generally institution dependent. Positive MRSA culture results can be reated 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[17], in addition to vancomycin administration at the time of surgery [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)

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 the 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[0].  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[0].

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 milligram per kilogram body weight. Examples of pediatric dosages include the following:  cefazolin 30mg/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.  In addition, the judicious use of vancomycin must be considered in order 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 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 usual preoperative surgical prophylaxis. 

Monitoring

Surgical site infections may occur for a variety of reasons including, but not limited to, incorrect antibiotic usage. When considering antibiotic prophylaxis practices, the correct antibiotic, dosage, timing of 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 take place to ensure no surgical site infections are occurring 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 the use of antibiotics that might result 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 [0].

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 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 and all clinicians participating in the care of surgical patients).

Level of evidence: II-III


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Preoperative Antibiotic Prophylaxis - Questions

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When is the best time to administer an antibiotic to prevent a surgical infection?



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When doctors use vancomycin as a preoperative prophylactic antibiotic, they should administer it within how many minutes before the start of surgery?



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In which of the following is a prophylactic antibiotic indicated?



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Which cephalosporin is usually given as a preoperative antibiotic in elective operative cases classified as clean such as hernia repair and mastectomy?



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Why are preoperative intravenous antibiotics given?



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Which of the following statements is true about antibiotics before cesarean section?



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When is the best time to give prophylactic antibiotics for surgery?



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A patient is going to have head and neck procedure. The patient is allergic to penicillin. When vancomycin is used as a preoperative prophylactic antibiotic, at what time period should it be administered?



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Which of these parenteral antibiotics is least appropriate for a pre-surgical prophylaxis regimen?



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A 28-year old female in the 39th week of her pregnancy has been in prolonged labor for over 16 hours. The obstetrician notes that the fetus is showing mild signs of distress and a semi-urgent cesarean section is planned in the next hour. To have the maximal benefit from antibiotics, the latest data suggest that they should be administered?



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Preoperative Antibiotic Prophylaxis - References

References

Antimicrobial Stewardship in Surgery: Challenges and Opportunities., Tarchini G,Liau KH,Solomkin JS,, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017 May 15     [PubMed]
W-Dahl A,Robertsson O,Stefánsdóttir A,Gustafson P,Lidgren L, Timing of preoperative antibiotics for knee arthroplasties: Improving the routines in Sweden. Patient safety in surgery. 2011 Sep 19;     [PubMed]
Gyssens IC, Preventing postoperative infections: current treatment recommendations. Drugs. 1999 Feb;     [PubMed]
Galandiuk S,Polk HC Jr,Jagelman DG,Fazio VW, Re-emphasis of priorities in surgical antibiotic prophylaxis. Surgery, gynecology     [PubMed]
AlBuhairan B,Hind D,Hutchinson A, Antibiotic prophylaxis for wound infections in total joint arthroplasty: a systematic review. The Journal of bone and joint surgery. British volume. 2008 Jul     [PubMed]
Stefánsdóttir A,Robertsson O,W-Dahl A,Kiernan S,Gustafson P,Lidgren L, Inadequate timing of prophylactic antibiotics in orthopedic surgery. We can do better. Acta orthopaedica. 2009 Dec     [PubMed]
Varacallo MA,Mattern P,Acosta J,Toossi N,Denehy KM,Harding SP, Cost Determinants in the 90-Day Management of Isolated Ankle Fractures at a Large Urban Academic Hospital. Journal of orthopaedic trauma. 2018 Jul     [PubMed]
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