Week 11 - Antibiotics for Surgical Procedures Flashcards
Where do 80% of nosocomial infections occur?
Urinary tract – foley catheters
Respiratory system – ventilators and VAP
Bloodstream – IV catheters
What are the patient related risk factors for surgical site infections?
- Age extremes <5 or >65
- Poor nutritional status
- Diabetes mellitus AND periop glycemic control (<200)
- Peripheral vascular disease
- Tobacco use (quit 4-8 weeks preop reduces SSI 50%)
- Coexisting infections
- Altered immune response
- Corticosteroid therapy
- Preoperative skin preparation (scrub and shave)
- Preoperative length of stay (longer preop stay greater risk of infection)
What are the facility related risk factors for surgical site infections?
- Experience of surgeon (volume-outcome relationship)
- Technique (Open vs laparoscopic procedure)
- Length of surgery
- Type and method of sterilization of instruments
- Perioperative normothermia
- Appropriate antibiotic dosing and re-dosing as needed
What is the ideal antimicrobial agent?
Acts on the pathogen and not the host
Does this via:
- Unique cellular structures and biochemical pathways
- Common pathways but altered affinities for certain components
- Prodrugs that are converted by only the pathogen
What does mismanagement of prophylactic antibiotics lead to?
- Increased risk of surgical site infection and hospital acquired infections
- Increased surgical morbidity and mortality
- Increased cost
- Associated with the rise in resistant infections nationwide
*inappropriate use continues to be a major problem for surgical patients
What are the risk factors for microbial resistance?
Antibiotics (2nd largest class of prescribed medications)
Extended/inappropriate use of antibiotics
Transmission of infection
What are the different antimicrobial spectrums of activity?
Narrow Spectrum: effective against Gm+ OR Gm- microbes
- works well for specific organisms and most surgical prophylaxis
- lowers risk of developing superinfections
Extended Spectrum: affects Gm+ AND Gm- bacteria
Broad Spectrum: affects Gm+ AND Gm- bacteria AND other microorganisms
- greater risk of superinfections
- don’t typically give in OR
What are the common narrow spectrum antimicrobial agents?
Clindamycin* Vancomycin* Bacitracin Macrolides Metronidazole PCN G PCN V Polymyxins
What are the common extended spectrum antimicrobial agents?
Cephalosporins* Aminoglycosides Extended PCNs Fluoroquinolones Imipenem
What are the common broad spectrum antimicrobial agents?
Chloramphenicol
Sulfonamides
Tetracyclines
Trimethoprim
Bactericidal vs Bacteriostatic
Bactericidal = agents KILL the microbes (killing infection that occurs requires bactericidal)
*MBC - minimal bactericidal concentration
Bacteriostatic = agents INHIBIT GROWTH of microbes (surgical prophylaxis requires bacteriostatic)
*MIC - minimal inhibitory concentration – surgical dosing
- Type of microbe is important
- Chosen antimicrobial’s spectrum of activity is important
- Antimicrobial level in the blood should exceed the MIC by 2-8x to provide prophylaxis against infection
What common antimicrobial agents are bactericidal?
Aminoglycosides Bacitracin* Daptomycin Fluoroquinolones Imipenem* Isoniazid Metronidazole Penicillins* Cephalosporins* Polymyxins Rifampin Vancomycin*
What common antimicrobial agents are bacteriostatic?
Clindamycin* Erythromycin Nitrofurantoin Sulfonamides Tetracyclines Trimethoprim
When is Chlorhexidine skin prep bactericidal and when is it bateriostatic?
Bacteriostatic = low concentrations
Bactericidal = high concentrations
What percent of iodine based skin prep is bactericidal?
Broad spectrum bactericidal at 1%
*higher concentrations cause necrosis
What are the common antibiotics mechanism of actions?
Cell Wall Synthesis:
- Beta Lactams (popular surgical prophylaxis): PCN, Cephalosporins, Carbapenems, Monobactams
- Vancomycin, Bacitracin
- Cell Membrane: Polymyxins
Nucleic Acid Synthesis:
- Folate synthesis (sulfonamides, trimethoprim)
- DNA Gyrase (quinolones)
- RNA Polymerase (rifampin)
Protein Synthesis:
- 30S Subunit (tetracyclines, aminoglycosides)
- 50S Subunit (macrolides, clindamycin, linezolid, chloramphenicol, streptogramins)
What are beta-lactam antibiotics?
Broad spectrum antibiotics that contain a beta-lactam ring in the structure
–Penicillins – Cephalosporins – Monobactams – Carbapenems –
What are the different Penicillins?
Derived from Penicillium fungi
PCN-G = IV form — PCN-G = PCN-G-K (K is for potassium – beware high doses)
PCN-V = PO form
- there is an IM form
- allergic to one PCN – allergic to all PCN
When are Penicillins the drug of choice?
- Pneumococcal infections
- Streptococcal infections
- Meningococcal infections
- Highly effective treatment for syphilis
- Actinomycosis and clostridial infections that result in gas gangrene
- Prophylactic for patients with history of rheumatic fever and surgery or dental work to treat transient bacteremia
How are PCNs excreted?
Renal excretion = Rapid (60-90% of an IM dose is excreted within 1 hour) – plasma concentration decreases to 50% its peak within 1 hour
10% GFR
90% renal tubular secretion
- if renal failure, need to adjust dose
- anuria increases elimination T1/2 of PCN-G by 10x
What are Cephalosporins (Gen 1-3) active against?
First generation = mostly active against Gram+ bacteria
Successive generations = more active against Gram-
*increasing affinity for Gm- resulted in decreased affinity for Gm+
What are Cephalosporins mechanism of action?
Bactericidal via interruption of cell wall synthesis
-more resistant to Beta-Lactamases
Disrupt B-Lactam ring and inhibit activity
~5-10% (rare) may have cross-reactivity with PCNs and/or Carbapenems (lack of suitable alternatives has forced use of Cephalosporins in these pts)
- allergic reactions in 1-10% of patients
- cross reactivity between Cephalosporins (all-for-one)
What is PCN resistance due to?
Bacterial production of Beta-lactamase enzymes that hydrolyze the Beta-lactam ring, rendering the antimicrobial inactive
*Methicillin, Oxacillin, Nafcillin, Cloxacillin, and Dicloxacillin are not hydrolysis susceptible to hydrolysis and will frequently work against these organisms – these drugs are used in infections caused by staphylococci
What is resistance to Cephalosporins due to?
Inability to penetrate the site of action
What is an example of a first generation cephalosporin? How is it administered? How is it excreted?
Cefazolin
Poor PO – reasonable IM absorption and well tolerated – IV is best
1st Gen excreted largely unaltered by the kidneys
-decrease dose in renal failure
What is an example of a second generation cephalosporin?
Cefoxitin and Cefuroxime
- Extended activity against Gm- bacteria
- Shorter T1/2
- Excreted unchanged by the kidney
*Cefuroxime is only 2nd gen good for treating meningitis
What is an example of a third generation cephalosporin?
Cefotaxime
- resist beta-lactam hydrolysis
- achieves CSF levels and good for meningitis
- Elimination T1/2 one hour requiring more frequent redosing
What are Monobactams (Axtreonam) effective against?
Effective ONLY against Gram- bacteria (Neisseria, Pseudomonas)
Resistant to some beta-lactamases
*not absorbed PO – must be given IM or IV
What are Carbapenems useful for?
Imipenem, Meropenem, Ertapenem, Doripenem
Useful for multi-drug resistant infections (hospitalized pts)
- Broader spectrum than other beta-lactams
- Less affected by mechanisms of antibiotic resistance
What can Clindamycin cause?
Pseudomembranous Colitis
- reserved for severe infections not controlled by other less toxic antibiotics
- d/c if significant diarrhea
What effect can high doses of Clindamycin have at the NMJ?
Produces pre- and post-junctional effects at NMJ
*these effects cannot be readily antagonized with calcium or AChE drugs
High doses can result in profound and long-lasting neuromuscular blockade in the absence of nondepolarizing muscle relaxants
What is vancomycin?
Bactericidal glycopeptide that impairs cell wall synthesis of Gram+ bacteria
- works well PO for enterocolitis because it’s poorly absorbed from the GI tract
- Drug of choice for MRSA infections
IV 10-15mg/kg – MUST be given slowly over 60 minutes
*sustained plasma concentration for 12 hours - rarely re-dose in OR
What does a fast administration of vancomycin result in?
A large histamine release
- Red Man’s syndrome
- Severe hypotension
- Cardiac arrest?
What are Fluoroquinolones good for?
Ciprofloxacin is highly effective for urinary and genital tract infections (prostatitis and GI infections)
Upper and lower respiratory infections
Soft tissue, bone, and joint infections
*high blood levels and good tissue penetration make it a good antibiotic
What is the mechanism of action of chlorhexidine?
Disrupts cell membranes of bacteria
Effective against G- and G+
- persists on skin to provide continuous coverage
- 2% is more effective than povidine-iodine as hand scrub
How quickly does iodine act?
Rapid acting antiseptic that, IN THE ABSENCE of, organic material kills bacteria, viruses, and spores
1% iodine kills 90% bacteria in 90 seconds
5% iodine kills 90% bacteria in 60 seconds
>7% iodine may cause cutaneous burns
***MUST DRY to be effective
What do you need to be aware of/check for with surgical antibiotic prophylaxis?
- Ensure surgical antimicrobial orders reflect published evidence
- Achieve plasma concentration prior to incision
- Infusion must be completed prior to tourniquet inflation
- Maintain intra-op MIC plasma concentration until skin closure***
- Interval dosing based on the particular antibiotic administered
- Additional dose anytime EBL exceeds 1500 mL since last dose
What is the most commonly used antibiotic for surgical prophylaxis?
Cefazolin (1st gen cephalosporin)
*wide therapeutic index and low incidence of side effects, cost effective
What antibiotics are typical backups for B-lactam allergy?
Clindamycin
Vancomycin
Gentamicin
What are antibiotic re-dosing intervals based on?
2-2.5 times the T1/2 in the general population with normal renal function
*doses are based on ideal body weight
What perioperative antibiotics need to be re-dosed every 2 hours?
Ampicillin-sulbactam
Ampicillin
Cefoxitin
Piperacillin-tazobactam
What perioperative antibiotics need to be re-dosed every 3 hours?
Cefotaxime
What perioperative antibiotics need to be re-dosed every 4 hours?
Aztreonam
Cefazolin
Cefuroxime
What perioperative antibiotics need to be re-dosed every 6 hours?
Cefotetan
Clindamycin
What are the four main factors for surgical site infections?
- Host Fitness (ability to the host to defend)
- Inoculum (amount of pathogen transmitted)
- Wound Microenvironment (conditions at the wound site) – necrotic tissue, stitches, the inoculum itself
- Pathogen Virulence (ability of the pathogen to cause disease)
What is the most common causes of bacteremia or fungemia in hospitalized patients?
IV access catheters
*S. aureus and S. epidermidis
What is the mechanism of action of Penicillins?
Bactericidal – Cell Wall Synthesis Inhibitors
- Interfere with the synthesis of peptidoglycan – essential component of cell walls of susceptible bacteria
- Decrease the availability of an inhibitor of murein hydrolase such that the uninhibited enzyme can then destroy (lyse) the structural integrity of bacterial cell walls
- resistant Gm- bacteria prevent access to sites where synthesis of peptidoglycan is taking place
What are the broad-spectrum penicillins?
2nd Gen PCNs: Ampicillin, Amoxicillin (broad spectrum)
3rd Gen PCNs: Carbenicillin (extended spectrum)
4th Gen PCNs: Mezlocillin, Piperacillin, Azlocillin (extended - broadest spectrum)
- wider range of activity than other PCNs – bactericidal against Gm- and Gm+ bacteria
- inactivated by penicillinase produced by certain bacteria – not effective against most staphylococcal infections
What are Clavulanic acid, Sulbactam, and Tazobactam?
Beta-lactam compounds that bind irreversibly to the Beta-lactamase enzymes
*inactivate Beta-lactamase enzymes causing the bacteria to be sensitive to PCNs
What are Erythromycin or Clindamycin an effective alternative for?
Treatment of streptococcal pharyngitis, bronchitis, and pneumonia in patients who can’t tolerate PCNs or Cephalosporins
*Erythromycin prolongs QT – torsades de pointes
What are Bacitracins?
a group of polypeptide antibiotics effective against a variety of Gm+ bacteria
- use limited to topical application
- treat furunculosis, carbuncle, impetigo, suppurative conjunctivitis, and infected corneal ulcer
