Prophylactic Antibiotic Administration
Summary by Noah Alcodray MD, 01.12.22
Overview
It would be unusual for an anesthesia provider to administer a medication in the absence of a thorough knowledge of the pharmacology, proper dosing, and indications for that medication, but this is often the case with parenteral prophylactic antibiotics
Prior to 2006, prophylactic antibiotics were often given by nursing staff on the floor or in preop
Role was transitioned to the anesthesia team following the “100,000 Lives Campaign” (by reliably delivering the correct perioperative antibiotics at the proper time) and the creation of CMS Physician Quality Reporting System (formerly Physician Quality Reporting Initiative)
Surgical site infections are a major perioperative complication and add huge costs to health care system (approx. $9.89 billion)
SSI most common reason for hospital readmission after surgery
Anesthesiologists contribution to SSI reduction: frequent handwashing, maintenance of intraoperative normothermia, neuraxial anesthesia, modest glucose control, induced hypercarbia, increased inspired oxygen concentrations, timely administration of prophylactic antibiotics, minimizing OR traffic, avoiding blood transfusion, effective postoperative pain control
Bolded interventions are part of Surgical Care Improvement Project (SCIP) and CMS PQRS
Primary defense against pathogens is oxidative killing by neutrophils via bactericidal superoxide radical. Oxygen is a substrate for this process and the reaction, catalyzed by NADPH-linked oxygenase, is PO2 dependent
Hypercarbic augmentation of CO thought to raise tissue oxygen pressure suggesting reduction in SSI
2010 JAMA article from Stulberg et. al (published while at CWRU) found the following:
Among hospitals in the Premier Inc Perspective Database reporting SCIP performance, adherence measured through a global all-or-none composite infection-prevention score was associated with a lower probability of developing a postoperative infection. However, adherence reported on individual SCIP measures, which is the only form in which performance is publicly reported, was not associated with a significantly lower probability of infection.
Beta-lactams
Includes: penicillins, cephalosporins, carbapenems
MOA: binding to cell wall synthesis enzymes known as penicillin-binding proteins (PBPs), inhibiting peptidoglycan synthesis
Mainly “time-dependent killing” = fraction of time drug concentration exceeds minimum inhibitory concentration (MIC)
Minimal postantibiotic effect (ability to continue bacterial killing after drug concentration below MIC)
Beta-lactams highly protein bound and only free drug has antibacterial activity. Unbound drug must pass through capillary membrane, diffuse through interstitial fluid, reach pathogens, and bind PBP in the bacterial wall. THIS TAKES TIME
Timing
2 major factors at play
High tissue levels are desired at skin incision, which is more likely to occur when antibiotics are given approximately 15 to 45 minutes out
Tissue levels above MIC are desired for the duration of the operative procedure, which is more likely to occur when the antibiotic is given immediately before incision
Overwhelming majority of available studies are consistent with an optimal preincision infusion time window between 15 and 45 minutes
Redosing
Plasma half-life of cefazolin is 1.2 – 2.2 hours
American Society of Health-System Pharmacists recommend redosing interval of 2 half-lives, hence the 4 hours we utilize for cefazolin
In one study, lack of redosing was greatest noncompliance measured (45.1%)
Some authors suggest continuous infusion after initial bolus dose to maintain time-dependent killing concentration profile
Biofilm can develop in as little as 6 hours
Continuous infusion justified in cases for pacemaker, mesh, prostheses etc.
Surgeries associated with significant blood loss and fluid requirements will decrease antibiotic tissue concentrations via dilution or elimination
It is suggested to calculate patients total blood volume using Lemmens formula and redosing at a 30% EBL
Lemmens Formula
Blood Volume (cm3/kg)= 70/[sqrt(BMI/22)]
Cases which utilize a tourniquet and in which a SSI would be catastrophic (e.g. total knee replacement), consider an additional tourniquet release dose
Weight-Based Dosing
While there are suggestions for cefazolin dosing for patients <70kg or >120kg, modifications for other beta-lactams rarely discussed
Cefazolin dose (grams) = 0.135 x H (meters) x sqrt[ W (kg)]
When to Avoid Prophylactic Antibiotics?
Antibiotic use not without potential harm (C. diff, resistance, etc)
All antibiotic decisions should be discussed with surgical team but numerous situations in which antibiotics not indicated
Clean orthopedic procedures on extremities without instrumentation, clean head and neck procedures (thyroidectomy, lymph-node excision), low risk ASA I or II patients undergoing elective cholecystectomy, laparoscopic oophorectomies, tonsillectomies, cystoscopies
Penicillin Allergy
Often cefazolin is avoided and clindamycin or vancomycin given in patients with history of penicillin allergy
However, this is only recommended in situations where history is consistent with IgE-mediated (urticaria, angioedema, anaphylaxis, bronchospasm) or severe non-IgE-mediated reaction (interstitial nephritis, toxic epidermal necrolysis, hemolytic anemia, SJS)
Even in the above situations, questionable if cefazolin needs to be avoided as cross-sensitivity dependent on similarity of R1 side chains between penicillins and cephalosporins
This is not the case with cefazolin
Cephalexin, cefaclor, cefadroxil have similar R1 side chains with penicillin
Other considerations
Antibiotic selection should target most likely pathogens
Cefazolin is usually drug of choice as skin pathogens (Staphylococcus aureus, Staphylococcus epidermidis) most frequent SSI culprit in clean surgeries
Top 5 most commonly reported pathogens are (1) Staphylococcus aureus, (2) coagulase-negative staphylococci, (3) Escherichia coli, (4) Enterococcus faecalis, and (5) Pseudomonas aeruginosa