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Orthopedic and Podiatry Perioperative Antibiotics
Introduction
Perioperative antibiotics are crucial for achieving positive outcomes and preventing infections in orthopedic or podiatry surgery. These antibiotics are typically administered in the perioperative setting, which includes 3 phases—preoperative, intraoperative, and postoperative.[1] The selection of specific antibiotic prophylaxis for each phase depends on various factors, including the nature of the surgery (elective or trauma), the type of fracture (open or closed), potential contaminants, and required bacterial coverage. Surgeons must also consider relevant contraindications, such as prior allergic reactions and potential adverse effects.
While nearly all elective orthopedic or podiatric surgery cases use perioperative antibiotics, a recent survey revealed a disparity in surgical antibiotic prophylaxis practices among surgeons.[2] In non-arthroplasty cases, a dose of cefazolin is typically administered within 30 minutes before the first incision. Arthroplasty surgeons often augment this with preoperative vancomycin to counter methicillin-resistant Staphylococcus aureus (MRSA) infections. However, trauma cases necessitate a unique approach to antibiotic management due to the high variability of mechanisms of injury and the diverse types of wounds surrounding fractures, which leads to more complex algorithms for the choice of antibiotics.
Issues of Concern
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Issues of Concern
Closed Versus Open Fractures
In the trauma setting, each fracture requires assessment for skin compromise and is classified as either closed or open. Closed fractures do not violate the skin and are not subject to the same contamination risk as open fractures. Prophylaxis for closed fractures is typically sufficient with a first-generation cephalosporin, often cefazolin, administered before surgical incision and followed by 3 additional doses over the subsequent 24 hours postoperatively.
Open fractures present a significant risk to limb integrity, and bacterial exposure may lead to osteomyelitis, nonunion, and potential amputation.[3] Gustilo and Anderson (GA) introduced a classification system to guide the treatment of open fractures. GA type I fractures involve open wounds of less than 1 cm. GA type II fractures feature open wounds ranging between 1 and 10 cm. GA type III fractures are divided into 3 subdivisions—A, B, and C.
GA type IIIA fractures have open wounds larger than 10 cm or result from high-energy mechanisms of injury. GA type IIIB fractures require soft tissue flap rearrangement for wound coverage, whereas GA type IIIC fractures involve vascular injury. GA type IIIB or type IIIC fractures may be smaller than 10 cm but are still categorized as higher grades if the injury necessitates soft tissue coverage or involves vascular damage, respectively. Treatment for GA type III fractures typically involves a cephalosporin (such as cefazolin) or ceftriaxone and an aminoglycoside (such as gentamycin).
Coverage Considerations
Surgical infections predominantly stem from bacterial sources, with fungal, parasitic, or viral etiologies being rare occurrences. Bacteria are classified as either gram-positive or gram-negative, with few exceptions. Antibiotic selection for postoperative infection prevention should be guided by the likely pathogens, primarily targeting gram-positive skin flora such as s Staphylococcus aureus, S epidermidis, Streptococcus pyogenes, and S pneumoniae.[4] In shoulder surgery, consideration should also be given to the coverage of Cutibacterium acnes (formerly known as Propionibacterium acnes) should be considered.[5][6] The most common antibiotics used perioperatively in orthopedic and podiatric surgery are cefazolin, ceftriaxone, vancomycin, clindamycin, penicillin, and ciprofloxacin.
In arthroplastic surgery, the combination of cefazolin and vancomycin is controversial. Initially, vancomycin prophylaxis was recommended in institutions with a high MRSA prevalence.[7] However, recent research indicates limited benefits and increased risks with the addition of vancomycin to cefazolin, particularly when it is not dosed correctly.[8][9][10]
Open wounds contaminated with fresh water are susceptible to infection by Pseudomonas aeruginosa, a gram-negative rod. Such injuries necessitate additional antibiotic coverage with a fluoroquinolone, typically ciprofloxacin or levofloxacin.[11] In contrast, open wounds contaminated with salt water may be infected by various organisms, including vibrio species, and should be treated with doxycycline.[11]
Open wounds resulting from farm injuries are frequently contaminated with barnyard soil or fecal matter, increasing the risk of infection with Clostridium species. Clostridium is a spore-forming organism that is effectively treated with a member of the penicillin family, often Penicillin G.[12]
Aminoglycosides are used in the treatment of GA type III open injuries. Suzuki et al reported that gram-negative bacteria were isolated in 77% of GA type III injuries, underscoring the need for an effective agent with strong gram-negative coverage.[13]
Vancomycin is indicated for use in individuals who are confirmed or potential carriers of MRSA.[9]
Allergy Considerations
Considering that cefazolin is the standard antibiotic prophylaxis for orthopedic and podiatric procedures, it is important to address patients with severe allergies to cefazolin. In such cases, clindamycin is frequently used as a secondary option due to its similar spectrum coverage.[14]
Historically, cefazolin was avoided in patients with beta-lactam allergies due to cross-reactivity reported to be 8%.[15] However, more recent studies indicate a lower cross-reactivity rate of 0.7% and demonstrate fewer surgical site infections (SSIs) in patients with a documented penicillin allergy who received cefazolin compared to alternatives such as clindamycin or vancomycin.[16][17] Patients with proven or possible MRSA colonization who exhibit an allergy to vancomycin should receive treatment with alternative antibiotics such as daptomycin, tigecycline, or linezolid.[18]
Adverse Effects
All antibiotics routinely used for perioperative prophylaxis in orthopedic and podiatric surgery may lead to mild adverse effects, including gastrointestinal upset. However, judicial selection of antibiotics is essential when there is a risk of life-threatening or organ-damaging effects. Cefazolin has the potential to induce anaphylaxis, while ceftriaxone may lead to anaphylaxis and hematemesis. Vancomycin is associated with red man syndrome and nephrotoxicity.[19] Clindamycin may cause pseudomembranous colitis.[20][21] Penicillin may result in adverse reactions such as hives, laryngospasm, and anaphylaxis in hypersensitive patients.[22] Gentamicin carries risks of nephrotoxicity, tinnitus, and vestibular dysfunction.[23] Fluoroquinolones have been documented to increase the risk of tendon rupture and cause arrhythmias.[24][25]
Mechanism of Action
Cefazolin: Cefazolin, belonging to the first-generation cephalosporin family, functions by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins, consequently leading to cell lysis. The drug exhibits effectiveness against gram-positive bacteria, notably S aureus, group A Streptococcus, and S pneumoniae.[26]
Ceftriaxone: Ceftriaxone belongs to the third-generation cephalosporin family that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, ultimately leading to cell lysis. The spectrum of ceftriaxone is much broader than that of cefazolin and other first-generation cephalosporins, thus targeting both gram-positive and gram-negative bacteria.
Vancomycin: Vancomycin exhibits bacteriostatic activity by binding the D-ala-D-ala protein in the bacterial cell wall. This drug is effective against gram-positive bacteria and is the first-line treatment for MRSA infections.[9]
Clindamycin: Clindamycin is classified as a lincosamide, and it functions by binding to the 23S RNA of the 50s ribosomal subunit, thereby inhibiting protein synthesis and exerting bacteriostatic activity. This drug is notably effective against gram-positive bacteria, including staphylococci and streptococci, as well as anaerobic bacteria, including Bacteroides species.[27] However, it does not provide coverage against MRSA or gram-negative bacteria.[28]
Gentamycin: Gentamycin is a member of the aminoglycoside family, and it functions by binding to the 16S RNA of the 30s ribosome, causing mistranslation of polypeptide chains and eventual cell death.[29] Aminoglycosides are recognized for their broad-spectrum activity, covering gram-positive and gram-negative bacteria, as well as mycobacteria.
Penicillin: Penicillins are a family of bactericidal agents that function by binding to penicillin-binding proteins, thereby inhibiting cell wall synthesis. They demonstrate efficacy against gram-positive bacteria, including Clostridium species, but have limited effectiveness against gram-negative bacteria and are ineffective against organisms producing beta-lactamases.
Ciprofloxacin: Ciprofloxacin is a member of the fluoroquinolone family. This drug inhibits the function of DNA gyrase and DNA topoisomerase, leading to DNA synthesis inhibition and bacteriolysis. The drug is effective against gram-negative bacteria, particularly P aeruginosa and E coli.
Timing
The current guidelines recommend administering surgical antibiotic prophylaxis within 60 minutes before the surgical incision or within 120 minutes for antibiotics requiring slower infusion times, such as vancomycin.[30][31] A part of the Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE) study assessed the effects of antibiotics administered within specific 30-minute increments around the time of hip and knee replacement surgeries. The study revealed that the lowest rates of SSIs were observed when the antibiotic was administered within a 30-minute window before the skin incision.[32] Postoperatively, antibiotics should be continued for no more than 24 hours in elective cases where the patient remains under observation or inpatient care, such as during evaluation by a physical therapist. Notably, it is crucial to adhere to dosing guidelines to maintain appropriate pharmacokinetics, for instance, administering cefazolin 2 g intravenously (IV) every 8 hours.
The use of postoperative oral antibiotics in the outpatient setting is controversial, with limited available data. Currently, standardized recommendations for oral antibiotics do not exist in the current literature. Frederick et al discovered no statistically significant difference in patients undergoing foot and ankle surgery who did or did not receive postoperative oral antibiotics.[33] Conversely, DeFrancesco et al observed that high-risk patients experienced benefits from 1 week of extended oral antibiotics, resulting in reduced rates of prosthetic joint infections.[34] Future randomized controlled trials may provide further clarity on the subject of oral antibiotics following outpatient surgery.
In the trauma setting, special consideration is given to antibiotic administration timing, necessitating a fourth phase termed "post-injury" dose, administered after the presentation but before initiating pre-operative protocols. The literature shows that administering antibiotics within 1 hour of the injury yields superior outcomes compared to delayed treatment.[35][36] Furthermore, perioperative antibiotic administration should adhere to a schedule based on the timing of the initial dose. GA type I and type II injuries necessitate perioperative prophylaxis for 24 hours, while GA type III injuries require antibiotic administration for 72 hours during the postoperative period.
The frequency of administration for each antibiotic is determined by its half-life. Cefazolin, with a half-life of 1.8 hours, is administered every 8 hours. Ceftriaxone, with a reported half-life between 5.8 and 8.7 hours, is given every 24 hours. Vancomycin, with a bi-phasic half-life, has an initial half-life and a terminal half-life of 6 hours and is administered every 8 hours. Clindamycin, with a half-life of 2.4 hours, is administered every 8 hours. Gentamicin, with a half-life of 3 hours, is administered every 8 hours. Penicillin G, with a reported half-life of 30 to 60 minutes, is administered every 4 to 6 hours. Ciprofloxacin, with a half-life of 5 hours, is administered every 12 hours.
Available Dosages
IV administration is the preferred method for all antibiotics during the perioperative period. Dosing guidelines for adult patients are as follows:
- Cefazolin is dosed at 1 g for patients with a body weight of less than 60 kg, 2 g for patients with a body weight of 60 to 120 kg, and 3 g for patients with a body weight of more than 120 kg.[37]
- Ceftriaxone is dosed at 2 g.[38]
- Vancomycin is dosed at 15 to 20 mg/kg.[19] Pharmacists make dosage adjustments, and serum trough levels are typically monitored.
- Clindamycin is dosed at 600 mg for patients with a body weight of less than 75 kg and 900 mg for patients with a body weight of more than 75 kg.[39]
- IV penicillin G is dosed at 2 million units for surgical prophylaxis.
- Gentamicin is dosed at 6 mg/kg.[40]
- IV ciprofloxacin is dosed at 400 mg.[41]
When tailoring antibiotic prophylaxis for the pediatric population, accurate dosing is essential, utilizing the patient's age, weight, and body mass index (BMI) according to the manufacturer's dosing schedule.
Clinical Significance
Orthopedic and podiatric surgeries, particularly those involving implanted metal hardware, are at risk for SSIs. The reported annual incidence of SSIs ranges from 1.9% to 3.6% in orthopedic surgery and 3.4% to 4.2% in podiatric foot and ankle surgery.[42][43][44] Long-term complications of SSIs include prolonged morbidity, disability, and increased mortality. SSIs are the primary cause of unplanned hospital readmissions among surgical patients.[45] Prophylactic antibiotic use has become a standard practice to mitigate the risk of SSIs and their associated complications.[14][2]
Patients undergoing arthroplasty are susceptible to prosthetic joint infection, with reported incidence rates ranging from 0.1% to 11.1% of cases. Prosthetic joint infection can lead to subsequent surgeries, reduced quality of life, amputation, permanent disability, and increased mortality.[46][47] Often, vancomycin is administered in the preoperative phase to mitigate the risk of prosthetic joint infection secondary to S aureus.
Although prophylactic antibiotic administration is crucial to safe surgical practice, it poses inherent risks to patients. Systemic antibiotic use may disrupt the gut microbiota and cause severe cutaneous adverse reactions, opportunistic infections, or allergic reactions.[22][48] Furthermore, overuse of antibiotics may lead to the emergence of multidrug-resistant organisms, with potentially devastating consequences.[49] Therefore, it is crucial to carefully select and administer appropriate perioperative antibiotics for orthopedic or podiatric patients to mitigate the risk of surgical site infections or prosthetic joint infections while minimizing adverse reactions and preventing the proliferation of multidrug-resistant organisms. Antibiotic stewardship is a collective responsibility shared by all healthcare team members.
Enhancing Healthcare Team Outcomes
Patients undergoing orthopedic or podiatric surgery face the risk of SSIs, which can be mitigated through perioperative antibiotic prophylaxis spanning the preoperative, intraoperative, and postoperative phases. Tailored antibiotic coverage is necessary for specific scenarios, such as vancomycin for MRSA carriers, penicillin for contamination with barnyard soil, and clindamycin for patients with cefazolin allergies. Ensuring the indicated antibiotics are administered via the correct route, at the proper dosage, and within the appropriate timing is essential.
Effective perioperative antibiotic prophylaxis relies on consistent practice and collaboration among an integrated healthcare team. This team typically includes primary surgeons, surgical assistants, anesthesia personnel, surgical technicians, circulating nurses, floor nurses, pharmacists, advanced practitioners, and any other clinicians involved in the patient’s care. Each member of the team plays a crucial role in ensuring appropriate prophylaxis and its timing, mitigating adverse events related to allergies or toxicity, and optimizing patient outcomes. Collaboration among these diverse healthcare professionals is essential for successful perioperative antibiotic management.
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