Pharmacology of Prophylactic Antibiotics in GI Surgery Flashcards
What is a surgical site infection?
Defined as an infection related to an operative procedure that occurs at or near the surgical incision within 30 days of the procedure or within 90 days if the prosthetic material is implanted at surgery
What is the epidemiology of surgical site infections?
Up to 6% of patients –> prolonged hospitalization & increased costs
–> SSIs are the third most frequent cause of all nosocomial infections
What is the role of prophylactic administration of antibiotics?
Decreases the risk of infection during and after many surgical procedures
What is the aim of prophylactic antibiotic therapy?
prevent infections in high-risk patients or procedure
What does the drug choice depend on?
Depends on the type of surgery, the nature of pathogenic organisms (including resistance patterns), intrinsic patient risk factors and cost
What is the spectrum of the prophylactic antibiotic therapy?
Must be active against the most common microbes for a given surgical site
When should prophylactic antibiotic therapy be given (timing)?
Must be administered at an appropriate time before surgery (1 hour) to ensure adequate drug levels at the surgical site prior to and for the duration of the operation, and also be given for the shortest effective period to minimize adverse effects, emergence of resistance and cost
When is prophylactic antibiotic therapy stopped?
Usually, within 24 hours after the surgery
What kind of therapy is preferred when it comes to prophylactic antibiotic therapy?
Monotherapy targeting known susceptible microbes is preferred
What kind of drugs is the first line for prophylactic antibiotic therapy?
First generation cephalosporins because of their spectrum of activity, safety and cost
What is an example of first-generation cephalosporins?
Cefazolin
When are combination therapies needed?
In special cases, to avoid resistance to certain monotherapies, accelerate the microbial kill reduce toxicity
What kind of therapy is often needed in GI surgeries?
Combination therapy is often needed in GI procedures to increase the spectrum of activity to include both aerobes and anaerobes
What are examples of combination therapies used in GI procedures?
- Metronidazole and Cefotaxime
- Metronidazolee and Aminoglycoside (Gentamicin or Amikacin)
What is the spectrum of activity of Metronidazole?
Only active against anaerobes (and protozoa)
What is the spectrum of activity of Cefotaxime/cefazolin?
Active against aerobes (like gram-negative enteric bacilli)
What medication is given to patients who are allergic or resistant to cephalosporins?
Aminoglycosides
Vancomycin –> in cases of MRSA
What is the reason behind the increase in resistant organisms and Candida causing SSIs?
- The widespread use of prophylactic and empiric antibiotics
- Increased severity of illness
- Greater numbers of immunocompromised patients undergoing surgical procedures
What are examples of beta lactams?
Penicillins
Cephalosporins
What are examples of penicillins?
Amoxicillin
What are examples of cephalosporins?
Cefotaxime
Cefazolin
What is the mechanism of action of beta lactams?
Inhibition of bacterial cell wall synthesis
–> Bind to PBPs located inside the bacterial cell wall
–> Inhibits peptidoglycan cross-link formation in bacterial cell wall
–> Cell wall lysis mediated by bacterial cell wall autolytic enzymes (autolysins)
What is the coverage and spectrum of activity of penicillins?
Gram + or -
Anaerobes
What is the coverage and spectrum of activity of cephalosporins?
First and second generations –> Gram + and -
Third and fourth generations –> Mostly gram -
What is the coverage and spectrum of activity of carbapenems?
Broad gram -
Anaerobes
What are the PK of beta-lactams? (4)
- Acid-stable beta-lactams can be given orally, while others are administered parenterally
- Distributed into most body tissues and fluids.
- Penterate inflamed meninges and reach therapeutic levels within the CSF
- Eliminated via the kidney
What is the half-life of Cefazolin?
Short half-life –> 1 to 2 hours
What are the adverse effects of beta-lactams?
- Mainly hypersensitivity reactions (benign rash to anaphylaxis)
- Exhbiti cross sensitivity or cross allergenicity
What is the MOA of aminoglycosides?
- Enter bacterial cells by diffusing through aqueous channels formed by porin proteins
- Bind irreversibly to the 30s ribosomal subunits and then inhibit bacterial protein synthesis
What are the characteristics of aminoglycosides? (3)
- Rapidly bacteriocidal
- Bacterial killing is concentration dependent
- Exhibit post-antibiotic effect (PAE)
What is the coverage of aminoglycosides?
Broad gram -
What are the PK of aminoglycosides?
Not absorbed orally
Given IV
Eliminated via the kidneys as intact form
What are the adverse effects of aminoglycosides?
Nephrotoxicity
Ototoxicity
Neuromuscular blockade –> paralysis
What are examples of aminoglycosides?
Gentamicin
What are examples of glycopeptide antibiotics?
Vancomycin
Teicoplanin
What is the MOA of glycopeptide antibiotics?
Bactericidal –> binds to the precursor units of bacterial cell walls –> inhibiting their synthesis
RNA synthesis is also inhibited
What is the coverage of glycopeptide antibiotics?
Effective only fro gram + bacteria
What is Teicoplanin also effective against?
Type B strains of vancomycin-resistant enterococci
What are the PK of glycopeptide antibiotics?
- Vancomycin is administered IV by IV slow infusion (needs to be given 2 hours prior to GI surgery)
- Vancomycin has a long half-life
- Eliminated via the kidney
What is the half-life of Vancomycin?
4 to 6 hours
What are the therapeutic sessions of Glycopeptide antibiotics?
Particularly useful against penicillin and methicillin-resistant S. Aureus and for treating gram + infections in penicillin-allergic patients
How are Glycopeptide antibiotics given for antibiotic-associated C. difficile colitis?
Given orally –> not absorbed but for local effect in the GIT
What are the adverse effects of Glycopeptide antibitics?
Otootoxicty
Nephrotoxicity
Which glycopeptide antibiotic is less toxic?
Teicoplanin is less toxic than vancomyxin
What do Glycopeptide antibiotics require?
Therapeutic drug monitoring
What is Metronidazole?
An antibiotic and antiprotozoal medication that is effective orally
–> Synthetic nitroimidazole
What are the indications for Metronidazole? (5)
- Anaerobic infections and mixed infections,
- surgical prophylaxis requiring anaerobic coverage
- C. difficile-associated colitis,
- H. pylori infection
- Duodenal ulcer disease
Which protozoa is Metronidazole used against? (3)
Trichomonas vaginalis
Amoebiasis
Giardiasis
What are common side effects of Metronidazole?
- Nausea
- Metallic taste
- Epigastric distress/ cramps
- Headaches
What are the contraindications of Metronidazole?
Avoid alcohol –> leads to a disulfiram-like reaction
What are the symptoms of disulfiram-like reactions?
Nausea
Vomiting
Flushing of the skin
Tachyacrdia
Shortness of breath
What is the MOA of Metronidazole?
Unionized metronidazole prodrugs are selective for anaerobic bacteria due to their ability to reduce metronidazole to its active form.
This reduced/active form covalently binds to DNA and disrupts its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death
Relatively little effect upon human cells or aerobic bacteria
Is post-operative use of prophylactic antibiotics recommended nowadays? Why?
NO
repeat antimicrobial dosing following wound closure is not necessary and may cause patient harm due to an increase in risk for the development of antimicrobial resistance
–> Prolonged post-op antibiotics may also increase the risk of AKI
In the case prophylaxis is continued after the surgery, when should it be stopped?
The duration should not exceed 24 hours
