A guide to antimicrobial prophylaxis in the surgical patient What comes after Ancef? A guide to antimicrobial prophylaxis in the surgical patient

Course Objectives Identify commonly used antibiotics in the surgical setting Describe the mechanism of action of commonly used antibiotics Identify common surgical pathogens Discuss current guidelines for antimicrobial prophylaxis during surgery

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Before we figure out what weapons we need to use we first need to know who the enemies are

Gram staining By Graevemoore at English Wikipedia, CC BY-SA 3.0 https://commons.wikimedia.org/w/index.php?curid=8477969 Gram staining is method we use to classify bacteria. The difference is in the cell wall. gram positive bacteria have a thicker peptidoglycan layer, so during the staining process, the crystal violet does not get rinsed away. Gram negative bacteria have a thinner peptidoglycan layer, so they dye gets washed away and they have a pink appearance. They tend to be more resistant to antibiotics than their gram negative counter part.

Meet Staph Aureus Aerobic gram positive cocci Is the primary cause of the majority SSI (up to 30 %) Staph aureus is ubiquitous. Part of the natural flora of the skin and mucous membranes. Colonization occurs in about 1 in 4 patients and increases the risk of SSI by up to 14 fold Harmless until it penetrates deeper tissues

Enzymes secreted by staph A. Coagulase: Converts fibrinogen into fibrin to form clots. Prevents phagocytosis. Staphylokinase: dissolves fibrin, spreads the bacteria Deoxyrobonuclease: breaks down DNA Beta-lactamase – degrades the beta lactam ring and causes drug resistance.

Other gram positive organisms Staph epidermis known for its bio slime and occurs in sternal wounds and prosthesis Streptococcus, commonly found in mouth throat skin and intestine are commonly found SSI bacteria and can cause hemolysis. Common subtypes include Streptococcus pyogenes and Enterococcus. Streptococcus pyogenes: Group A streptococcus is responsible for type II necrotizing fasciitis Enterococcus: present in the adult GI tract and account for a large amount of clean contaminated SSI All of these bacteria can be either aerobic or anaerobic

Anaerobic Gram positive bacilli Members of the clostridium species Cause tetanus and botulism, but are not common in surgical site infection Clostridium perfringens causes the surgical site infection known as “gas gangrene” C difficile occurs when the normal flora of the intestine are eliminated by prolonged antibiotic therapy- may lead to toxic megacolon Pockets of gas form below the skin

Gram positive cocci account for nearly 50% of all surgical site infections

Gram negative bacilli Primarily found in the intestines Account for about 20 % Of surgical site infections . Enterobacter spp, Escherichia coli (E coli ) Klebsiella pneumoniae

Anaerobic gram negative organisms: Bacteroides fragilis Most common anaerobe in intraabdominal infections Has the tendency to form capsules and are notorious for the formation of appendicitic abscess

Now that we know what we are fighting, let’s see what tools we have to use

Beta Lactam Antibiotics Are the most commonly prescribed antibiotic for surgical site infection They work by inactivating a set of enzymes that are necessary for cell wall synthesis These enzymes are called penicillin binding proteins (PBP) and different bacteria have anywhere between 4 and 8 of them Each PBP has a different function depending on the bacteria and each of the beta lactam drugs impact cell wall synthesis diffently Cover a broad spectrum of micro- organisms and we will look at them more closely later in the lecture Anaphylaxis is the primary concern Ancef is in this group but as you will see a ton of our antibiotics fall into this category

Beta Lactam Antibiotics Penicillins Narrow spectrum Not commonly used perioperatively Broad Spectrum Ampicillin Cephalosporins 1st Generation Cefazolin 2nd Generation Cefuroxime Cefoxitin Cefotetan 3rd Generation Cefotaxime Ceftriaxone 4th and 5th Generation Carbapenems Ertapenem Monobactams Aztreonam Beta lactamase inhibitors Sulbactam Tazocactam

Selection of antimicrobial agent Cefazolin Appropriate spectrum of activity Inexpensive Desirable side effect profile Appropriate duration of action The reason ancef is so popular is because it has a more narrow spectrum of activity that covers the most common surgical site pathogens.

Beta lactam allergy Patients who have a penicillin allergy generally react to either the beta lactam ring or the R group side chain 2% of patients who are skin test positive for penicillin have a cross sensitivity to cephalosporins There is a 1% chance of cross sensitivity with carbapenems There is no evidence of cross sensitivity with aztreonam All of these drugs are safe to use if the allergy is not IgE mediated The rate of cross sensitivity for cephazolin used to be 10%, but in the 70’s there was trace pcn in cephalosporins

Quinolones Levofloxacin Ciprofloxacin Bind to the enzymes that are involved with DNA synthesis leading to cell death Largest degree of activity is against gram negative bacilli and gram negative rods. Limited activity against staph and enterococcus Adverse effects include C-Diff colitis, peripheral neuropathy and tendon rupture

Aminoglycosides Gentamycin Works by inhibiting translocation of DNA to RNA Activity primarily against aerobic gram negative bacteria Nephrotoxic Ototoxic Neuromuscular blockade and is contraindicated in myasthenia gravis

Clindamycin (lincosamide antibiotic) Inhibits bacterial protein synthesis, and is bacteriostatic ( as opposed to bactericidal) Activity against MRSA, Gram positive bacteria and Anaerobes Adverse reactions: C-diff colitis

Metronidazole Mainstay of treatment for obligate anaerobic bacteria (C-Diff) Its low molecular weight allows it to pass easily into the cell and destabilize the DNA helix Can turn urine into a red brown color Can cause flushing and tachycardia and nausea on vomiting if given to patients who have had alcohol

Vancomycin A glycopeptide antibiotic Spectrum of activity include gram positive bacteria including MRSA Routine prophylaxis with vancomycin is not recommended for any surgical procedure in an effort to control vancomycin resistance Should be reserved for patients that are MRSA positive of institution that are experiencing clusters of MRSA. Adverse reaction includes red man syndrome Ototoxic nephrotoxic

Now lets put it all together

Recommendations

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Orthopedic procedures Procedures with implantation, the recommendation is cefazolin which covers gram positive staph and e-coli 2nd generation cephalosporin are equally as effective in preventing surgical site infection, but are more costly, and have a broader spectrum which may contribute to resistance and C-Diff Vancomycin and clindamycin are alternatives for patients with a beta lactam allergy

Orthopedic procedures not involving implantation Arthroscopy of the knee hand and foot have low infection rates These guidelines do not recommend antibiotics

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Cardiac procedures Recommendation: cefazolin or a 2nd generation cephalosporin (cefuroxime) Vancomycin or clindamycin is acceptable in a beta lactam allergy

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Thoracic Procedures Thoracic procedures can also carry the risk of pneumonia. Some studies indicate that ampicillin-sulbactam is more effective than cephalosporins The recommendation is cefazolin or ampicillin-sulbactam

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Urologic procedures The primary concern for urologic procedures entering the urinary tract is bacteriuria cased by E. Coli and other gram negative bacilli The recommendation is Fluoroquinolones. Procedures that enter the urinary tract through the skin will require cefazolin plus a strong gram negative like gentamicin or a fluoroquinolone

Surgeries of the bowel The natural flora of the bowel changes as you travel down the intestine Patients with a small bowel obstruction or appendicitis get treated the same way as patients undergoing bowel surgery Biliary Tract E. Coli (G-) Klebiella (G-) Enterococci (G+) Small Intestine Colon B fragilis (anaerobe) E coli

https://www.polleverywhere.com/clickable_images/lw8mrfczLZVyXKc Biliary tract E. Coli (G-) Klebiella (G-) Enterococci (G+) Small bowel E. Coli (G-) Large intestine B fragilis (anaerobe) E coli

Surgeries of the Gastrointestinal tract Biliary tract recommendations: Cefazolin. Studies show that there is no difference between 1st 2nd and 3rd generations cephalosporins Small Bowel recommendations: Cefazolin Unless there is small bowel obstruction then the recommendation is for a 2nd generation cephalosporin or cefazolin and metronidazole. Colorectal recommendations (including Appendectomy) 2nd generation cephalosporins or cefazolin and metronidazole

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Head and Neck procedures Clean head and neck procedures, as well as tonsillectomy and endoscopic sinus surgeries have a very low rate of infection, and do not require antibiotic prophylaxis Clean-contaminated, commonly head in neck cancer, are very complex do to the flora of the mouth, Recommendations for clean contaminated procedures 1st or 2nd generation cephalosporin with the addition of metronidazole For patients with a beta lactam allergy, clindamycin plus gentamycin covers the gamut.

Reference CDC. New York activities to prevent HAIs. http://www.cdc.gov/HAI/stateplans/state-hai-plans/ny.html. Accessed September 24, 2016. Qadan M, Cheadle WG. Common microbial Pathogens in surgical practice. Surgical Clinics of North America. 2009;89(2):295–310. doi:10.1016/j.suc.2008.09.002. Calderwood, SB. Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects. In: Up to Date, Hooper, DC. (Ed), UpToDate.Waltham, MA. (Accessed on August 28, 2016.) Solenski, R, SB. Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams. In: Up to Date, Adkinsen, NF. (Ed), UpToDate.Waltham, MA. (Accessed on Sept 02, 2016.) Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. American Journal of Health-System Pharmacy. 2013;70(3):195–283. doi:10.2146/ajhp120568. Hooper DC. Fluoroquinolones . In: Up to Date, Calderwood SB. (Ed), UpToDate.Waltham, MA. (Accessed on Sept 01, 2016.) Johnson M. Clindamycin: An overview In: Up to Date,Hooper DC. (Ed), UpToDate.Waltham, MA. (Accessed on August 21, 2016.) Johnson M. Metronidazole: An overview In: Up to Date,Hooper DC. (Ed), UpToDate.Waltham, MA. (Accessed on August 21, 2016.) Drew, R. Clindamycin: Vancomycin dosing and serum concentration monitoring in adults ,Hooper DC. (Ed), UpToDate.Waltham, MA. (Accessed on August 24, 2016.)