Antibiotics

Why Antibiotics?

In 1984 a study including 51 acute care hospitals in New York State found that surgical site infection (SSI) was the most common adverse surgical event (and the second most common adverse event overall). Perioperative antibiotic prophylaxis – administration of abx prior to surgery to prevent surgical site infections, but best practice also includes sterility (surgeon and instruments), skin prep (clipping hair, allowing skin antiseptic to dry) Barash, Paul G. Clinical Anesthesia. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2009. Print. SSIs- now a marker of quality of care in the US, Medicare no longer reimburses for certain SSIs (ie mediastinitis after cardiac surgery, SSIs post-bariatric surgery & some orthopedic procedures)

Timing of prophylaxis

Antibiotic therapy should be given within 60 min (ideally: 15-45 mins) prior to surgical incision for adequate serum drug tissue levels at incision. • Exception IV vanco/cipro (requires longer infusion) • If a proximal tourniquet is used, the entire antibiotic dose should be administered before the tourniquet is inflated. • Exceptions to pre-incision antibiotics: • check for active ongoing antibiotic therapy, may not be indicated for surgery, surgeon declined, or delay until after a specimen is sent for culture. Timing of prophylaxis Rates of Surgical-Wound Infection Corresponding to the Temporal Relation between Antibiotic Administration and the Start of Surgery • The number of infections and the number of patients for each hourly interval appear as the numerator and denominator, respectively, of the fraction for that interval. The trend toward higher rates of infection for each hour that antibiotic administration was delayed after the surgical incision was significant (z score = 2.00; P<0.05 by the Wilcoxon test). Classen DC, et. Al. (1992) The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. The New England Journal of Medicine 326:281-286.

Types of Wounds (per CDC/NHSN)

Clean procedures (1.3 to 2.9% rate of surgical site infection) • Uninfected operative wound closed primarily in which no inflammation is encountered and respiratory, GI, genital, or uninfected urinary tracts are not entered. • Common skin flora: CoNS, MSSA/MRSA and strep • Clean-contaminated procedures (2.4 to 7.7% rate of SSI) • Operative wounds in which the respiratory, GI, genital, or urinary tracts are entered under controlled conditions and without unusual contamination. • Common bugs are skin flora, gram-negative rods, Enterococci. If surgery involves a viscus, pathogens reflect endogenous flora of the viscus or nearby mucosa • Contaminated procedures (6.4 to 15.2% rate of SSI) • Open fresh, accidental wounds. Also, operations with major breaks in sterility, gross spillage from the GI tract, and incisions in which acute non-purulent inflammation is encountered • Dirty or infected (7.1 to 40.0% rate of SSI) • Includes old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera.

2017 SHC Surgical Antimicrobial Prophylaxis Guidelines

Surgery Preferred Agent Beta-lactam allergy Cardiac Surgery/Vascular/Thoracic Cardiac device insertion (PM implant) Other General Surgery (hernia, breast) Neurosurgery Orthopedics Plastic Surgery Cefazolin Vancomycin (preferred) Clindamycin can be used as an alternative. Based on 2015 SHC Antibiogram, 81% MSSA susc to clinda vs 100% MSSA susc to vanc Cardiac Surgery w/ prosthetic material Cefazolin + Vancomycin Vancomycin Gastroduodenal Cefazolin Vancomycin + Gentamicin Biliary Tract Cefazolin Metronidazole + Levofloxacin Colorectal, Appendectomy Cefazolin + Metronidazole Metronidazole + Levofloxacin Gynecological (hysterectomy/Cesarean) Cefazolin Clindamycin + Gentamicin Urology These are EMPIRIC abx recs when no preoperative urine cx available or culture negative. Ask urology team for recs. If clean: Cefazolin If clean contaminated (eg open or lap with ileal conduit)- cefoxitin If prosthetic material involved, should add gentamicin x1 dose Gentamicin + Clindamycin1 If clean: (skin incision only)- clinda1 If clean-contaminated: metronidazole + levofloxacin 1sub vanc for clinda if MRSA due to clinda poor urinary penetration Head & Neck Clean or ear/sinonasal: Cefazolin If contaminated (include oral mucosa breach)- Cefazolin+ Metronidazole Clindamycin *Based on 2013 consensus guidelines from American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS) and the Society for Healthcare Epidemiology of America (SHEA) Selected 2017 SHC Dosing and Re-dosing Guidelines Antimicrobial Recommended Dose Re-dosing (hrs) Notes Cefazolin <120kg- 2g >120kg- 3g Peds: 30mg/kg, max 2g 4 Can bolus over 3 minutes** Clindamycin 900mg 6 Give over 30 minutes Vancomycin <80kg – 1g 80-99kg- 1.25g 100-120kg- 1.5g >120kg- 2g Adult and Peds 15mg/kg 12 Give over 30-60 minutes, or <10mg/min; whichever is longer) Can be given 60-120min prior to incision (long half life) Ampicillin-Sulbactam 3g 2 Give over 15-30 minutes Aztreonam 2g 4 Cefoxitin 2g 2 Ceftriaxone 2g 24 Ciprofloxacin 400mg 8 Give over 60 minutes Contraindicated in pregnancy Ertapenem 1g 24 Give over 30 minutes Gentamicin 5 mg/kg (single dose) If CrCl<20, 2mg/kg (single dose or consult Rx) 24 Dilute to <1mg/cc Give over 30-120 minutes (risk of ototo/nephrotoxicity with bolus) Levofloxacin 500mg 24 Metronidazole 500mg 12 Give over 20-60 minutes *As a general rule, for drugs with a greater therapeutic index, you can administer them faster

Allergies and Interactions

Penicillins and 1st & 2nd generation cephalosporins have similar side change with some risk of cross-reactivity • Cephalothin (1st cephalosporin) marketed in 1964; cross-reactivity with penicillin allergy noted to be 5-10%. This over-generalization of cross-reactivity has resulted in the avoidance of all cephalosporins, not just cephalothin, in patients labeled as penicillin allergic • Some of this cross-reactivity is historically thought to be due to cross-contamination during manufacturing • True incidence of allergy in patients with a reported history of PCN allergy is less than 10%. • Only IgE-mediated reaction (type I, immediate hypersensitivity reactions) are true allergic reactions. • Encourage skin testing to simplify future antibiotic choices • The cross-reaction rate between PCN and 1st & 2nd cephalosporins is 1-10% • Cross-reaction rate between 3rd generation cephalosporins and PCN approaches 0%! • History of PCN allergy is a general risk factor for allergic manifestations to antibiotic administration that may not be specific to cephalosporins

Perioperative Antibiotic Decision Algorithm From Vorobeichik, et. al. Anesthesia & Analgesia, 2018

Allergies and Interactions • If the allergic reaction to PCN is only erythema or pruritis, many attendings still give a cephalosporin, but always check with your attending • However, hx of anaphylactic reaction to PCN is an absolute contraindication to cephalosporins. • Type 1 anaphylactic reaction to antimicrobials occur 30- 60 minutes after administration • Test dose: Not always done. However, it may be prudent to give 1ml of the antibiotic first to see if the patient will have a reaction. This test dose only decreases the anaphylactoid reaction, not anaphylaxis • Allergic reactions are more likely from neuromuscular blockers than antibiotics

Penicillin Allergy Pathway for Antibiotic Prescriptions

From Vaisman, et al. JAMA 2017

Endocarditis Prophylaxis

Patients at increased risk: – Prosthetic cardiac valve (including transcatheter-implanted prostheses and homografts) – Prosthetic material used for cardiac valve repair, including annuloplasty rings and chords – Previous history of infective endocarditis – Unrepaired cyanotic congenital heart disease or completely repaired congenital heart defect within the first 6 months. – Cardiac transplant patients who develop cardiac valvulopathy • Procedures at risk • Dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa (not all dental procedures) • Upper respiratory tract: only if it is incised or biopsied • Procedures on infected skin, skin structure, or musculocutaneous tissue • GI/GU: prophylaxis no longer recommended • Bacterial Endocarditis prophylaxis – Ampicillin 1-2gm IV, 30min prior to surgery AND Gentamicin 1.5mg/kg IV, 30min prior to surgery – IF PCN allergic, use cefazolin or ceftriaxone 1gm IV, or clindamycin 600mg IV • Mitral valve prolapse/HoCM/Bicuspid AV do not need prophylaxis because, while there is increased risk for IE, the most serious adverse outcomes of IE do not usually occur in patients with these conditions.

ITE tip

Which of the following antibiotics does NOT augment neuromuscular blockade? a. Clindamycin b. Neomycin c. Streptomycin d. Erythromycin Answer: d. Cephalosporins also do not affect neuromuscular blockade.