Exam 1: ABX Flashcards
(32 cards)
Goals and General Rules
- Inhibit microorganisms at concentrations that are tolerated by the host
- Seriously ill/immunocompromised select bactericidal
- Narrow spectrum before broad spectrum or combination therapy to preserve normal flora
- OR – use broad-spectrum, bc you want to kill what would infect the surgical area, or
- Or continue abx in the OR for when they’re due
-If doing cx’s during the case, they will likely want you to give the abx AFTER the cx has been taken
Antimicrobial Therapy and Anesthesia Practice: Why do we care
(3 main reasons)
o Prophylaxis before surgery:
- Anesthesia plays important role in timely administration of ABXs – w/i 1 hour of incision
- Reimbursement for quality care
o Potential for adverse reactions
-Hypersensitivity Reaction (dose independent)
-Direct organ toxicity (dose related)
-Potential for superinfections
-Identify patients at risk for complications
• Elderly – less organ fn, and won’t clear drugs quickly
• Parturient – cross BBB
o Cross-reactions with other medications we give
SSI definition
o SSI defined as an infection related to an 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
Factors that increase risk for devt of SSIs (surgical site infections)
o SURGICAL RISK
- Procedure Type
- Skill of surgeon
- Use of foreign material or implantable device
- Degree of tissue trauma
o PATIENT RISKS
- Diabetes
- Smoking use
- Obesity
- Malnutrition – low protein to support fns
- Systemic steroid use
- Immunosuppressive therapy
- Intraoperative hypothermia – constricts bv’s, slows metab rate, blood more viscous, won’t flow to the places it needs, oxy-hgb shifts to the L (hgb will hold on to O2, “Left, loves O2”)
- Type of surgery might lend itself to infxns - brain, bone vs. thyroid surgery – lots of lymph nodes in that area, relatively clean area
- Trauma – degree of tissue trauma
- Prosthetic heart valves
- Always weigh risk-benefit ratio
- Surgeon’s skill – less chance is quick, some sloppy
SSI Prevention tenets
o According to the literature most SSIs are preventable
o Surgical Care Improvement Project (SCIP)
o Anesthesia providers can make an impact on prevention through:
- Timely and appropriate use of antibiotics
- Maintenance of normothermia
- Proper syringe/med administration practices
SBE prophylaxis protocol
o Standard general prophylaxis:
- Amoxicillin 2gm PO
OR - IV amipicillin 2gm IV
o PCN allergic
- Clindamycin 600 mg IV
- Cefazosin 1gm IV (NOT IN pts with hypersensitivity to PCN)
o Use this protocol in ppl who have
- Heart valves
- Ppl who have have bacterial endocarditis in the past
- Transplants
- Congenital heart dz that has been unrepaired, or was repaired and still have defects
SSI (Surg Site Infection) Prevention
• 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
• Normothermia
- 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
o Glucose control is important in all surgical pts, but especially in cardiac surgery pt.
- Lots of instances of mediastinal site questions
- <200 mg/dl or even 160 as cutoff during surgery
Classes of Abx
• Types of antibiotics
o Antibiotics are categorized
o bactericidal if they kill the susceptible bacteria (usually preferred)
o bacteriostatic if they reversibly inhibit the growth of bacteria. (usually UTIs)
o In general the use of bactericidal antibiotics is preferred but many factors may dictate the use of a bacteriostatic antibiotic.
o When a bacteriostatic antibiotic is used the duration of therapy must be sufficient to allow cellular and humoral defense mechanisms to eradicate the bacteria.
• Bactericidal vs bacteriostatic
List some bactericidal and bacteriostatic drugs
• Bactericidal - PIMP VARB (F?)Q o Penicillin's & Cephalosporin's o Isoniazid o Metronidazole o Polymyxins o Rifampin o Vancomycin o Aminoglycosides o Bacitracin o Quinolones - Fluroquinolones?
• Bacteriostatic - CCM TTS o Chloramphenicol o Clindamycin o Macrolides (erythromycin/azithromycin) o Sulfonamides (sulfamethoxazole, trimethoprim) o Tetracyclines o Trimethoprim
PCN (1st generation) - MOA, organisms, excretion, DOA
Are they bactericidal or bacteriostatic?
(Basically PK)
“PCN - peptidoglycan prevention (no cell membrane) - probenecid (used for gout) prolongs renal excretion”
o Basic structure is a dicyclic nucleus that consists of a thiazolidine ring connected to a B-lactam ring
(Won’t ask us this in this way)
*Bascially cell membrane can’t form and bacterium can’t live
o **Bactericidal: Interferes with the synthesis of peptidoglycan which essential component to cell walls of susceptible bacteria. – inhibits the enzyme, which is needed to keep the bacterium intact. SO the contents will exude.
o Organisms
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
o 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
o Duration of Action
- Administration of probenecid (used to tx gout) will reduce renal excretion and prolong action
PCN Adverse Rxns
Hypersensitivity-most allergenic of all the antimicrobials (up to 10%):
• Rash +/or fever
• Hemolytic anemia
• Maculopapular rash (delayed)
• Immediate sensitivity: anaphylaxis
• Cross-sensitivity common with all penicillin drugs AND cephalosporins (3%) (due to common beta-lactam ring)
2nd generation PCNs (organisms and names of drugs)
o Organisms
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
- Wider range of activity
• Gram negative- bacilli - Haemophilus influenza
• E coli
o Amoxicillin
o Ampicillin
o ** patients with documented IgE mediated anaphylactic reactions the B-lactum antibiotics can be substituted with Clindamycin or Vancomycin – they should not get 2nd generation PCN!!!
Aside: As you go up in generation, you go up in price (ancef is cheap)
Cephalosporins
Are they bactericidal or bacteriostatic?
(Basically PK)
Cefazolin (will prob use most often)
o Bactericidal antimicrobials that inhibit bacterial cell wall synthesis and have low toxicity
- Broad spectrum activity
- Allergy incidence is 1-10%
- anaphylaxis is 0.02%
- cross reactivity with other cephalosporins
- Penicillin and Cephalosporin allergy 1-3%
***DO NOT USE if outright anaphylactic rxn. But if they can’t recall, you could be asked to give a test dose of a few 100 mg of it, then see if there’s a rxn, then infuse the rest of it
- Renal excretion
1st gen: cefazolin
2nd cefoxitin
3rd cefotaxime
All cephalosporins go into joints, and cross placenta.
Macrolides - name of drugs, and PK of “prototype” of this class (no SEs)
(Erythromycin, Azithromycin)
MACRO-GLIDES DOWN - increased peristalsis, cramps, N/V
MACRO QTC - prolonged repolarization, r/f Torsades
o Useful for patients with sensitivities to PCNs and cephalosporin drugs
- Compounds characterized by a macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached
- **Erythromycin is the Prototype
- Effective against Gram positive bacilli, pneumococci, streptococci, staphylococci, mycoplasma, chlamydia
o Erythromycin
- Bacteriostatic or bactericidal – depends on organism, or dose!
- Inhibits bacterial protein synthesis
- Metabolized by the cytochrome P-450 system and thus increase serum concentration of theophylline, warfarin, cyclosporine, methylprednisone and digoxin
- Excreted mostly in bile
- No need to alter dose in renal disease
Macrolides SEs
MACRO-GLIDES DOWN - increased peristalsis, cramps, N/V
MACRO QTC - prolonged repolarization, r/f Torsades
- GI intolerance - increases peristalsis (→ cramps!) And gastric emptying!
- Most common side effect
- Severe N/V can occur with IV infusion
- Gastric emptying
- Cholestasic hepatitis
- QT effects
- Prolongs cardiac repolarization
- Reports of torsades de pointes
- Thrombophlebitis (common with prolonged IV use)
Clindamycin
Bactericidal or bacteriostatic?
PK, SEs
CLINDA-COLITIS/C.Diff
CLIN-(non)Depolarizer. AChE won’t help.
CLIN (clean) DA RASH.
o Class- Linomycins
o Bacteriostatic
o Similar to Emycin in antimicrobial activity
o More active with anaerobes
o Pseudomembranous colitis → severe diarrhea should indicate discontinuation of therapy
(tx C.diff with vanco/flagyl)
o DOSING
- Only 10% of administered dose is excreted unchanged in urine the rest is inactive
- Decrease dose with severe liver disease
o Most commonly used in female GU surgeries
o Severe complications (GI) limit its use to infections that are difficult to treat
o SIDE EFFECTS
- Skin Rash
- Prolonged pre- and post-junctional effects at NMJ, even in the absences of NDMR (nondepolarizing muscle relaxant)
- Not antagonized with anticholinesterases or calcium → Concurrent administration with NDMR can produce long lasting, profound neuromuscular blockade
Vancomycin (general info)
Bactericidal or bacteriostatic?
Indications
Glycopeptide deriviative
o Bacteriocidal - Impairs cell wall synthesis
o Effective for Gram positive bacteria
- Severe staph infections
- Streptococcal, enterococcal endocarditis
- **DOC (drug of choice) for Methicillin resistant staph aureus (MRSA)
- Penicillin / Cephalosporin allergy
- Administered with aminoglycoside for endocarditis
o Renal excretion 90% unchanged in the urine
- Elimination ½ time is 6 hrs. and can be prolonged (up to 9 days) with renal failure patients
o Cardiac/Orthopedic procedures using prosthetic devices
o CSF and shunt related infections
o Dose
- 10-15 mg/Kg over 60 minutes - so must be starting it in the ICU before getting to the OR bc needs to run/finish within the 1st hour of surgery
- 1 Gram mixed in 250ml.
o Indications
- MRSA
- Endocarditis due to Strep. viridans or enterococci
- Patients allergic to β-lactams
- Use of vancomycin is typically reserved for Rx of bacterial infections resistant to other antibiotics, or patients with severe hypersensitivity to other indicated antibiotics. If bacteria become resistant to vancomycin, there are only a few other drugs that may be effective in treating the patient.
Vanco (PK and SEs)
- Very poor absorption upon oral administration
- IV administration (slowly over 1 hour)
- Renal excretion by glomerular filtration (80-90% in 24 hr)
- Slow CSF penetration unless there is meningeal inflammation
- Renal excretion 90% unchanged in the urine
- Elimination ½ time is 6 hrs. and can be prolonged (up to 9 days) with renal failure patients
SEs:
o Phlebosclerotic (vancomycin is irritating to tissue)
o Nephrotoxicity RARE unless concomitant treatment with other nephrotoxic drugs such as aminoglycosides)
o Ototoxicity when concentrations are >30mcg/ml (increased risk if giving with aminoglycosides)
o Hypersensitivity (maculopapular skin rash)
o Hypotension & “Red Man Syndrome” (flushing due to histamine release) if given IV in less than 30 minutes
o Administration of diphenhydramine 1mg/kg and Cimetidine 4mg/kg 1 hour before induction limits histamine related effects
4 types of Aminoglycosides
AMINO-mycins/kacins
amin-neo-nephro(toxic)
o Streptomycin & Kanamycin
-Limited uses & Frequent occurrence of vestibular damage
o Gentamicin
- Broader spectrum
- Toxic level – (> 9mcg/ml)
o Amikacin***
- Derivative of kanamycin
- Treatment for infections caused by gentamicin or tobramycin resistant gram-negative bacilli
- “Big gun” – used a lot in burn trauma.
o Neomycin** -
- Topically - Treatment for skin, eye and mucous membrane infections
- Adjunct therapy to hepatic coma
- Administered to decrease bacteria in intestine before GI Surgery
- Most nephrotoxic** of all aminoglycosides
- Used for irrigation/lavage – always know what they’re lavaging! Could be readily absorbed into the tissues (would need to let them know if the pt is renally insufficient)
Aminoglycosides (PK, bactericidal or bacteriostatic, SEs)
o Bactericidal
- Effective for aerobic gram negative & positive bacteria
- Mycobacterium Tuberculosis
o ***Generally prescribed as combination therapy with Betalactam antibiotic for Gm (-)
o Extensive renal excretion through glomerular filtration
o 2-3 hour elimination half time that is increased 20-40 fold with renal failure
o Side effects
- Limited by their toxicity
- Ototoxicity
- Nephrotoxicity
- Skeletal muscle weakness
- Potentiation of NDMR blockade
- Muscle weakness: inhibit the pre-junctional release of Ach and decreases post-synaptic sensitivity to the neurotransmitter (impact on patients with neuromuscular pathology ie.. Myasthenia gravis)
• Aminoglycosides and Potentiation of muscle relaxants
o IV Administration of aminoglycosides associated with potentiation of Non-depolarizing neuromuscular-blocking drugs.
o This paralysis is usually reversible with calcium gluconate or neostigmine.
o Effect may NOT be sustained!
o “re-curarization” - Could also re-paralyze the pt who has been reversed.
Fluroquinolones (names of drugs, uses, PK)
No SEs yet
o Ciprofloxacin - Treatment for Respiratory infections, tuberculosis and Anthrax
o Moxifloxacin - Suitable for long-acting treatment of acute sinusitis, bronchitis, complicated abdominal infections
- QT prolongation
- Peripheral neuropathy
- Psychosis
- Stevens-Johnson Syndrome – turn red & skin sloughs, mucus membranes slough
o Broad spectrum, bactericidal
o Effective for enteric Gram-negative bacilli and mycobacterium
o **Useful in treatment of complicated GI and GU infections
o Ciprofloxacin useful in treatment of variety of systemic infections including bone, soft tissue and respiratory tract
o GI absorption is rapid and penetration to body fluids and tissues is excellent
o Renal excretion, through glomerular filtration and renal tubular secretion
- Decrease dose in renal dysfunction
o Elimination ½ time 3-8hrs.
o Can inhibit P450 enzymes
“Your Achilles is on the FLOOR (flur)”
Fluroquinolones SEs
“Your Achilles is on the FLOOR (flur)”
“fluro-floxacin”
- Mild GI disturbances nausea/vomiting
- CNS dizziness, insomnia
- Tendon or Achilles rupture. YUCK. Any of the fluoroquinolones.
- Muscle weakness in patients with Myasthenia Gravis (any muscle-wasting agents)
Sulfonamides
Bacteridical vs bacteriostatic
Clinical uses
SEs
Sulfamethoxazole and trimethoprim
o Bacteriostatic
- Antimicrobial activity is due to the ability of these drugs to prevent normal use of PABA by bacteria to synthesize folic acid.
- Inhibit microbial synthesis of folate production
o Portion of drug is acetylated in the liver and other is renal excretion
o Renal disease-dose is reduced
o Clinical uses
- Urinary tract infections
- Inflammatory bowel disease
- Burns
o Side Effects
- skin rash to anaphylaxis
- Photosensitivity
- Allergic nephritis
- Drug fever
- Hepatotoxicity
- Acute hemolytic anemia
- Thrombocytopenia
- Increase effect of PO anticoagulant
metronidazole (Flagyl)
(lots of use in the OR)
o Bactericidal - Anaerobic Gram negative bacilli clostridium
o Useful for wide variety of infections
- CNS infections
- Abdominal and pelvic sepsis
- Pseudomembranous colitis (C-diff) (susceptible with clindamycin-induced c.diff → use flagyl and vanco to tx it)
- Endocarditis
o Well absorbed orally and widely distributed in tissue including CNS
o ** recommended for pre-op prophylaxis for colorectoal surgery
o PO or IV
o Side effects
- Dry mouth
- Metallic taste
- Nausea
- Avoid Alcohol
