Lecture 2: Antimicrobials CB Flashcards
Prevention Guidelines for Surgical Site Infections(SSI)
• SSI are second most common healthcare associated infection
• SSIs develop in 2-4% of 30 million surgical patients
• Represent approximately 14-16% of all hospital acquired infections annually in the U.S. and cost 9.8 billion dollars/year
• SSIs account for 3% of surgical mortality and lead to:
- SSI are second most common healthcare associated infection
- SSIs develop in 2-4% of 30 million surgical patients
- Represent approximately 14-16% of all hospital acquired infections annually in the U.S. and cost 9.8 billion dollars/year
- SSIs account for 3% of surgical mortality and lead to:
- Increased re-admissions
- increased length of stay (7-10 days)
- Increased hospital costs (additional $3000-29,000/per SSI diagnosis)
Surgical Site Infections(SSI)
• SSI defined as an infection related to a operative procedure that occurs at or near the surgical incision within X days of the procedure
• Purulent exudate draining from a surgical site
• A positive culture obtained from a surgical site that was closed initially
• A surgeon’s diagnosis of infection
• A surgical site that requires reopening due to at least one of the following signs or symptoms:
Surgical Site Infections(SSI)
• SSI defined as an infection related to a operative procedure that occurs at or near the surgical incision within 30 days of the procedure
• Purulent exudate draining from a surgical site
• A positive culture obtained from a surgical site that was closed initially
• A surgeon’s diagnosis of infection
• A surgical site that requires reopening due to at least one of the following signs or symptoms: tenderness, swelling, redness or heat
Surgical Site Infections(SSI) Prevention
• According to the literature most SSIs are ?
• Anesthesia providers can make an impact on prevention through:
• Timely and appropriate use of ?
• Maintenance of ?
• Proper syringe/med administration practices
• Perioperative ___________ control?
Surgical Site Infections(SSI) Prevention
• According to the literature most SSIs are preventable
• Anesthesia providers can make an impact on prevention through:
• Timely and appropriate use of antibiotics
• Maintenance of normothermia
• Proper syringe/med administration practices
• Perioperative glucose control
Risk for development of Surgical Site Infections(SSI)
SURGICAL RISK:
Procedure Type Skill of surgeon Use of foreign material or implantable device - no blood supply for abx Degree of tissue trauma
Risk for development of Surgical Site Infections(SSI)
PATIENT RISKS:
- Diabetes
- Smoking use
- Obesity
- Malnutrition
- Systemic steroid use (not proven)
- Immunosuppressive therapy
- Intraoperative hypothermia
- Trauma
- Prosthetic heart valves
- Extremes of age
- Hair removal
- Preoperative hospitalization
Surgical Site Infections(SSI) Prevention
Antibiotic Timing:
Antibiotic prophylaxis X hour(s) before ______ had the lowest rate of SSI
30-60 minutes before ______ is the ideal window for drug administration
Antibiotic Timing:
Antibiotic prophylaxis 1 hour before incision had the lowest rate of SSI
30-60 minutes before incision is the ideal window for drug administration
Surgical Site Infections(SSI) Prevention:
Normothermia – consider ____________ measures
Hypothermia is associated with adverse outcomes which include:
Compromised Neutrophil function→ vasoconstriction → tissue ________ and increased incidence of SSI
Normothermia – consider pre-warming measures
Hypothermia is associated with adverse outcomes which include: ⚫Increased blood loss ⚫Increased transfusion requirements ⚫Prolonged PACU stay ⚫Post-op pain ⚫Impaired immune function
Compromised Neutrophil function→ vasoconstriction → tissue hypoxia and increased incidence of SSI
Review slide 8!
Review slide 8!
Review slide 9!
Review slide 9!
Microbial resistance to anti-microbials
Major threat to public health:
• New Delhi Metallo-Beta Lactamase 1 _____
Mechanisms:
• Inc/dec active transport out of the bacterial cell and/or decrease the active transport into the cell?
• Structural changes in the drug _____
• Production of a drug antibiotic __________
• Enzymatic drug __________
• The more antibiotics are used the more __________ develops (in target bacteria and normal flora)
• Antibiotics are used extensively in hospitals
• 1.7 million patients acquire nosocomial infections almost 100,000 die
Major threat to public health:
• New Delhi Metallo-Beta Lactamase 1 Gene
- resists all abx but 2?
Mechanisms:
• Increase active transport out of the bacterial cell and/or decrease the active transport into the cell
• Structural changes in the drug target
• Production of a drug antibiotic antagonist
• Enzymatic drug destruction
• The more antibiotics are used the more resistance develops (in target bacteria and normal flora)
• Antibiotics are used extensively in hospitals
• 1.7 million patients acquire nosocomial infections almost 100,000 die
CDC “Campaign to Prevent Microbial Resistance”
What can we do?
- Encourage vaccination
- Limit invasive catheter use/vigilant infection control with placement
- Involve infectious disease experts
- Identify and target the specific microbe
- Quality control mechanisms for abx use
- Use local information about pathogen & sensitivity “antibiogram”
- Treat infection, not contamination or colonization
- Limit vancomycin use
- Avoid using when infection is cured or not likely present
- Isolation/infectious control procedures
- Hand washing
Antimicrobial Therapy and Anesthesia Practice: Signficance
⚫Prophylaxis before surgery:
Anesthesia plays important role in timely administration of ?
Reimbursement for quality care
⚫Potential for adverse reactions
Hypersensitivity Reaction (dose dependent/independent)
Direct organ toxicity (dose related/unrelated)
Potential for superinfections
Identify patients at risk for complications
⚫Cross-reactions with other medications we give
Signficance
⚫Prophylaxis before surgery:
Anesthesia plays important role in timely administration of ABXs
Reimbursement for quality care
⚫Potential for adverse reactions
Hypersensitivity Reaction (dose independent)
Direct organ toxicity (dose related)
Potential for superinfections
Identify patients at risk for complications
⚫Cross-reactions with other medications we give
Bactericidal
kill the susceptible bacteria
Bacteriostatic
reversibly inhibit the growth of bacteria
- In general the use of bacteri______ antibiotics is preferred but many factors may dictate the use of a bacteriostatic antibiotic.
- When a bacteri______ antibiotic is used the duration of therapy must be sufficient to allow cellular and humoral defense mechanisms to eradicate the bacteria.
- In general the use of bactericidal antibiotics is preferred but many factors may dictate the use of a bacteriostatic antibiotic.
- When a bacteriostatic antibiotic is used the duration of therapy must be sufficient to allow cellular and humoral defense mechanisms to eradicate the bacteria.
Types of antibiotics Bactericidal ~ most SSIs • Penicillin's & Cephalosporin's • Isoniazid • Metronidazole • Polymyxins • Rifampin • Vancomycin • Aminoglycosides • Bacitracin • Quinolones
Types of antibiotics Bactericidal ~ most SSIs • Penicillin's & Cephalosporin's • Isoniazid • Metronidazole • Polymyxins • Rifampin • Vancomycin • Aminoglycosides • Bacitracin • Quinolones
Types of antibiotics Bacteriostatic • Chloramphenicol • Clindamycin • Macrolides • Sulfonamides • Tetracyclines • Trimethoprim
Types of antibiotics Bacteriostatic • Chloramphenicol • Clindamycin • Macrolides • Sulfonamides • Tetracyclines • Trimethoprim
Antimicrobials and Anesthesiology
⚫Goals and General Rules
1. Inhibit microorganisms at concentrations that are tolerated by the?
2. MIC= ?
3. Seriously ill/ immunocompromised select bacteri____
4. Narrow spectrum before or after broad spectrum or combination therapy to preserve normal flora
Antimicrobials and Anesthesiology
⚫Goals and General Rules
1. Inhibit microorganisms at concentrations that are tolerated by the host
2. MIC= Minimum Inhibitory concentration to be effective
3. Seriously ill/ immunocompromised select bactericidal 4. Narrow spectrum before broad spectrum or combination therapy to preserve normal flora
Antimicrobials: Selective toxicity
Exploit cellular biological differences between microbes and mammals……
- Bacterial cell wall
- Bacterial enzyme inhibition
- Bacterial ribosome
Beta-Lactam Antibiotics:
Penicillins
Cephalosporins
Carbapenems
Beta Lactams: Mechanism of Action
Weaken bacterial cell wall
• Bind to penicillin binding proteins (only expressed during bacterial proliferation~atively dividing)
- Activate autolysins (decrease inhibition of murein hydrolase – enzymatic destruction of cell wall)
- Inhibit (transpeptidases) enzyme needed for cell wall synthesis and integrity
Penicillin
• Basic structure is a dicyclic nucleus that consists of a thiazolidine ring connected to a _________ ring
• Several subtypes based on structure, B-lactamase activity, and spectrum ?
• Bacteri_____
Penicillin
• Basic structure is a dicyclic nucleus that consists of a thiazolidine ring connected to a B-lactam ring
• Several subtypes based on structure, B-lactamase activity, and spectrum
• Bactericidal
Penicillin
• Allergic reactions are the principle concern- most common cause of drug allergy (Allergy incidence is 1-10% of patients)
• ___________ (.004-.04% with 10% mortality)
- Laryngeal edema, bronchoconstriction, severe hypotension
• May occur on 1st _________ (PCN contamination in food supply)
• ** patients with documented IgE mediated anaphylactic reactions the Beta lactam antibiotics can be substituted with ?
Penicillin
• Allergic reactions are the principle concern- most common cause of drug allergy (Allergy incidence is 1-10% of patients)
• Anaphylaxis (.004-.04% with 10% mortality)
• Laryngeal edema, bronchoconstriction, severe hypotension
• May occur on 1st exposure (PCN contamination in food supply)
• ** patients with documented IgE mediated anaphylactic reactions the Blactam antibiotics can be substituted with Clindamycin or Vancomycin
Penicillin - G (NOT Ampicillin): Excretion
• Renal excretion is rapid/slow: plasma concentration inc/dec 50% in 1st hour
• X% glomerular filtration
• X% renal tubular secretion
• _______ increases elimination half-time by 10 fold
• Adjust ______ in renal failure
• Administration of _________ will reduce renal excretion and ________ action
Penicillin - G (NOT Ampicillin): Excretion
• Renal excretion is rapid: plasma concentration decreases 50% in 1st hour
• 10% glomerular filtration
• 90% renal tubular secretion
• Anuria increases elimination half-time by 10 fold
• Adjust dose in renal failure
• Administration of probenecid will reduce renal excretion and prolong action
Broad Spectrum Penicillin: Second generation
- Amoxicillin
* Ampicillin - 50% excreted unchanged by the kidney 6 hours after admin
Even more Broad Spectrum Penicillin: Third generation
Organisms
• Same as second generation + ?
Carbenicillin
• Elimination half time is ?
• X% excreted unchanged by the kidney
• High/low sodium load (30—40 mg/caution in ___)
• Hypo_______
• Metabolic ________
• _________ bleeding time despite nml plt count
Broad Spectrum Penicillin: Third generation
Organisms
• Same as second generation + ?
• Pseudomonas aeruginosa and Proteus
Carbenicillin
• Elimination half time is 1 hour (2 hours renal disease)
• 85% excreted unchanged by the kidney
• High sodium load (30—40 mg/caution in CHF)
• Hypokalemia
• Metabolic alkalosis
• Prolonged bleeding time despite nml plt count
Beta-Lactamase Resistant Penicillins
Agents:
Spectrum of Activity:
• Broad/Narrow spectrum agents = ?
• Binds irreversibly to ____________ enzymes (large side group sterically hinders ____________ from cleaving ____________ ring
Beta-Lactamase Resistant Penicillins
Agents:
• Dicloxacillin
• Nafcillin (penetrates CNS; 80% secreted in the bile/good for pts w/renal dysfunction)
• Oxacillin
Spectrum of Activity:
• Narrow spectrum agents (Staph & Strep)
• Binds irreversibly to B-lactamase enzymes (large side group sterically hinders B-lactamase from cleaving B-lactam ring)
Beta-Lactamase Resistant Penicillins
• Nafcillin
- penetrates ?
- X% secreted in the bile/good for pts w/ _____ dysfunction
• Nafcillin
- penetrates CNS
- 80% secreted in the bile/good for pts w/renal dysfunction
B-Lactam/B-Lactamase inhibitor combinations:
- Ampicillin/Sulbactam (Unasyn®)
- Amoxicillin/Clavulanic Acid (Augmentin ®)
- Ticarcillin/Clavulanic Acid (Timentin ®)
- Pipercillin/Tazobactam (Zosyn ®)
- pt will end up with diarrhea
- *we want to preserve these from resistance!
Cephalosporins: Class
• Beta-lactam antibiotics
Cephalosporins
• Favorable or unfavorable therapeutic index?
• Favorable therapeutic index
Cephalosporins
• Bacteri_____
• Bactericidal
Cephalosporins: MOA
Same as pcns!
Bind to penicillin binding proteins
• Activate autolysins
• Inhibit (transpeptidases) enzyme needed for cell wall synthesis and integrity
Cephalosporins
1st & 2nd generation cephalosporins:
3rd & 4th generation cephalosporins:
4th generation cephalosporins:
*Beta lactimase susceptibility inc/dec as you move from the 1st to 4th generation
Cephalosporins
1st & 2nd generation cephalosporins:
Gram positive activity
3rd & 4th generation cephalosporins:
Gram negative activity & activity against anaerobes & ability to penetrate the BBB into CSF
4th generation cephalosporins: (EXPENSIVE)- maintain good gram neg. activity (including pseudomonas)
Retains gram positive activity of earlier generation cephalosporins
*Beta lactimase susceptibility also decreases as you move from the 1st to 4th generation
Cephalosporins: Examples From Each Generation
First generation =
• Cephalexin, cefazolin
Cephalosporins: Examples From Each Generation
Second generation =
• Cefuroxime, cefoxitin, cefotetan
Cephalosporins: Examples From Each Generation
Third generation =
• Ceftazidime, ceftriaxone, cefotaxime (BBB)
Cephalosporins: Examples From Each Generation
Fourth generation – (broadest) =
• Cefepime
Cephalosporins: Examples From Each Generation Fifth generation (or 3rd generation depending on the source) =
• Ceftaroline (MRSA coverage)
Broadest Cephalosporin =
• Cefepime
Cephalosporin MRSA coverage =
• Ceftaroline (MRSA coverage)
