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

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

9. Gram staining
By Graevemoore at English Wikipedia, CC BY-SA 3.0
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.

10. 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

11. 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.

12. 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

13. 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

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

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

16. 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

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

18. 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

19. 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

21. 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.

22. 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

23. 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

25. 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

27. 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

29. 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

31. 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

33. Now lets put it all together

34. Recommendations

36. 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

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

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

41. 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

43. 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

44. 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

45.
Biliary tract E. Coli (G-)
Klebiella (G-)
Enterococci (G+)
Small bowel
E. Coli (G-)
Large intestine
B fragilis (anaerobe)
E coli

46. 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

48. 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.

49. Reference
CDC. New York activities to prevent HAIs. Accessed September 24, 2016.
Qadan M, Cheadle WG. Common microbial Pathogens in surgical practice. Surgical Clinics of North America ;89(2):295–310. doi: /j.suc
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: /ajhp
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.)