Antimicrobials Flashcards
1
Q
Facts about SSI?
A
- SSI most common healthcare associated infection
- SSI develop 2-4% of 30 million surgical patient
- represent 14-16% of all hospital acquired infections annually in use and cost 9.8 bllio dollars/year
- 3% surgical mortality and lead to
- increased readmission
- increased length of stay (7-10 days)
- increased hospital costs (additional $3000-29k per diagnosis)
2
Q
What defines a SSI?
A
- Infection r/t operative procedure that occurs at or near the sx inc within 30 days of procedure
- purulent exudate draining
- positive culture obtained from sx site that was closed initially
- surgeon’s dx of infection
- sx site that requires reopening d/t at least one of following signs
- tenderness
- swelling
- redness
- heat
3
Q
Are SSIs preventable?
A
most are preventable
more difficult in immunosuppressed/ or when vascular supply is decreased
4
Q
How can anesthesia providers impact SSI prevention?
A
- Timely and appropriate use abx
- maintenance of normothermia
- underestimate; up to 50% prevention
- colder patient increase ROI
- underestimate; up to 50% prevention
- Proper syringe/med administration practices
- perioperative glucose control
- particularly CT cases and also GI (29–> 14% risk of infection)
5
Q
What are some surgical risks for devleoping SSI?
A
- Procedure type (ie GI vs cataract)
- skill of surgeon (big impact)
- use of foreign material or implantable device
- ortho, pacemaker, heart valve, don’t have blood supply
- risk of infection increase bc can’t treat with abx
- ortho, pacemaker, heart valve, don’t have blood supply
- degree of tissue trauma
6
Q
What are patient risks for devleoping SSI?
A
- DM
- Smoking use
- obesity
- malnutrition
- systemic steroid use (long term)
- immunosuppressive therapy (chronic)
- intraoperative hypothermia
- trauma
- prosthetic heart valves
- extremes of age
- hair removal
- preop hospitalizations
major underlying theme is good vascular supply
7
Q
When should antibiotics be timed in OR?
A
- Antibiotic prophylaxis 1 hour before incision had the lowest rate of SSI
- 30-60 min before incision is the ideal window for drug admin
8
Q
What adverse outcomes is hypothermia associated with?
A
- 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
9
Q
What are some SCIP measures?
A
- SCIP -Inf 1- prophylactic abx received within 1 hour sx incision
- SCIP INf2- prophylactic abx selection for surgical patient
- making sure it’s appropriate
- SCIP 3- Prophylactic abx d/c’ed within 24 h after surgery end time
- SCIP 4- Cardiac sx patient with controlled 6am postop glucose <200
- SCIP 5- Postop wound infection dx during index hospitalization
- SCIP 6- Sx patient with appropriate hair removal
- SCIP 7- Coloretal sx patient with immediate postop normothermia
10
Q
What is the new delhi metallo- beta lactamas 1 gene?
A
- Beta lactamase has resistanc eto pretty much every abx except 2
- Mechanism
- increase active transport out of bacterial cell and or decrease the active transport into the cell
- structural changes in drug target (PCN binding protein)
- changes how PCN binds to bacteria
- production of drug antibiotic antagonist- beta lactamase
- enzymatic drug destruction
- the more abx are used, the more resistance develops (in target bacteria nd normal flora)
- can share resistance with other bacteria
- abx are used extensively in hospitals
- 1.7 mil pt acquire nosocromial infeciton, almsot 10,0000 die
11
Q
What are some CDC priorities to prevent microbial resistance?
A
- Flu vaccine
- protection against sequellae
- limit invasive catheter and use vigilant infection contorl with placement
- involve infectious disease experts
- id and target speicfic microbe
- quality control mech for abx use
- use local info about pathogen and sensitivity “antibiogram”
- treat infection, not contamination or colonization
- limit vanc use
- avoid using when infection is cured or not likely present
- isolation/infectious control procedures
- hand washing
12
Q
Antimicrobial therapy and anesthesia implications?
A
- Prophylaxis before sx
- anesthesia plays important role in timely admin of ABX
- reimbursement for quality care
- Potential for adverse reactions
- hypersensitivity reaction (dose independent)
- one drop of medicine will cause anaphylaxis
- if PCN anaphylaxis, avoid any beta lactams
- direct organ toxicity (dose related)
- potential for super infections
- id patients at risk for complications
- hypersensitivity reaction (dose independent)
- cross reaction with other meds we give
13
Q
WHat’s bacteriostatic?
A
Keep bacteria from replicating so we can allow the immune system to work
- antiobiotic can only do so much without the immune system
- when used, the duration of therapy must be long enough to allow cellular and humoral defense mechanisms to eradicate the bacteria
14
Q
What’s bacteriocidal?
A
Drugs that actually kill bacgteria directly
15
Q
What are some bactericidal drugs?
A
- PCN and cephalosporins
- Isoniazid
- metronidazole
- polymyxins
- rifampin
- vanc
- aminoglycosides
- bacitracin
- quinolones
16
Q
WHat are some bacteriostatic abx?
A
- Chloramphenicol
- Clindamycin
- Macrolides
- sulfonamides
- tetracyclines
- trimethoprim
17
Q
Goals and general rules for antimicrobials and anesthesiology?
A
- Inhibit microorganisms at concentration that are tolerated by the host
- MIC= Minimum inhibitory concentration
- seriously ill/immunocompromised select bactericidal
- narrow specturm before broad spectrum or combo therapy to preserve normal flora
- can cause 2nd super infection like c diff
18
Q
Basic for how antimicrobials work?
A
- Selective toxicity
- exploid cellular biological diff between microbes and mammals
- METHODs:
- bacterial cell wall- we don’t have cell wall
- bacterial enzyme inhibition- ex, folic acid formation- those enzymes aren’t present in us. bacteria, however, makes folic acid from PABA
- bacterial ribosome
- just different enough that we can target it
- bacterial cell wall- we don’t have cell wall
19
Q
What are some beta lactam examples?
A
PCN
Cephalosporin
Carbapenems
20
Q
MOA of beta lactam abx?
A
- Weaken bacterial cell wall
- bind to pcn binding proteins (only expressed during bacterial proliferation)
- Active autolysins ( decrease inhibition of murein hydrolasw- enzymatic destruction of cell wall)
- actually inhibit murein hydrolase, this allows autolysins to work
- Inhibit transpeptidases enzyme- needed for cell wall synthesis and integrity
- can’t form cross bridges with peptidoglycan strands
- weakens cell wall
21
Q
Diff between gram - and +?
A
- Gram- has extra outer membrane
- harder for some drugs to penetrate outer membrane
22
Q
What is basic structure of PCN?
Bactericidal or bacteriostatic?
Allergies?
A
- Basic structure is dicyclic nucleus that consists of thiazolidine ring connected to B-lactam ring
- several subtypes based on structure, B lactamase activity and spectum
- Bactericidal
- Allerigc reactions are principles concern (1-10%)
- anaphylaxis only 0.004-0.04% patient exposed iwth a 10% mortality
- laryngeal edema, bronchoconstriction, severe hypotension
- may occur on 1st exposure
- Organisms (don’t need for test…)
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
23
Q
Excretion PCN?
A
- Renal excretion rapid (PCN G)
- plasma concentrationd ecreases 50% in 1st hour
- 10% glomerular filtration
- 90% tubular secretion
- Anuria increases elimination half-time by 10 fold
- adjust dose in renal failure
- administration of probenecid will reduce renal excreiton and prolong action
- (used this to advantage in WWII d/t limited supply of PCN)
24
Q
What are second generation penicillins? Examples?
A
- Expand spectrum but increased risk of secondary infection from normal flora
- Gram (-) bacilli–> h influenza
- e. coli
- Amoxicillin
-
Ampicillin
- 50% excreted unchanged by kidney 6 hours after admin
-
Organisms
- pneumococcal
- meningococcal
- streptococcal
-
actinomycosis
*
25
Q
Third generation PCN? Advese effects?
A
- Organism
- same as second + pseudomonas aeruginosa and proteus
- Example- carbenicillin
- elimination half time 1 hour (2 hours renal dx)
- 85% excreted unchanged by kidney
- high sodium load
- hypokalemia
- metabolic alkalosis- concerned especially in anesthsia
- prolonged bleeding time despite normal PLT count
Not used often. Need risk/benefit analysis. lots of adverse effects
26
Q
What are beta lactamase resistant PCN?
Agent? How does it work?
A
- Agents:
- dicloxacillin
- Nafcillin
- penetrates CSF 80% secreted in bil (good renal dys.)
- Oxacillin
- Spectrum of activity?
- Narrow spectrum agents
- binds irreversibly to b lactamas enzymes
- large side gorup sterically hinders b lactamase form cleaving b-lactam ring
-
Gram positive activity- streptococci and staphylococci
- no gram -
27
Q
What are some b-lactam/b-lactamase inhibitor combo drugs? When do we use them?
A
- Combo of beta lactam ring with beta lactamase inhibitor
- Ampicillin/Sulbactam (Unasyn)
- Amoxicillin/Clavulanic Acid (augmentin)
- Ticarcillin/Clavulanic acid (Timentin)
- Pipercillin/Tazobactam (Zosyn)
- Braod spectrum agnets
- gram positive
- gram negative
- anaerobe
Don’t give zosyn before every case because you knock out native flora (= lots diarrhea/yeast infection)
also want to preserve this combo drugs for when we need it
28
Q
What are cephalosporins?
static or cidal?
MOA?
A
- Beta lactam antibiotics
- favorable therapetuic index
- Bactericidal
- MOA- bind to PBP
- Activate autolysins
- inhibit transpeptidases enzyme needed for cell wall syntheis and integrity
- once you disturb cell wall, water rushes in and bacteria bursts
- MOA- bind to PBP
- Differenct b/w drugs depends on side chains
- can be expensive and can access diff areas (ie BBB)
29
Q
What is the activity of 1st and 2nd generation cephalosporins?
A
- More gram positive activity
- beta-lactamase susceptible
30
Q
What is activity of 3rd and 4th generation cephalosporins?
A
- Increase gram negative actiivty
- increase activity against anaerobes
- ability to penetrate the BBB into CSF
ID docs like to keep aside for serious infections that aren’t reacting
Can be very expensive
31
Q
Examples of each generation of cephalosporin?
A
- First generation
- cephalexin, cefazolin
- Second generation
- cefuroxime, cefoxitin, cefotetan
- Third generation
- ceftazidime, ceftriaxone, cefotaxime
- Fourth generation (broadest)
- cefepime (Neurosurgery use)
- Fifth gen
- Ceftaroline (MRSA coverage)
32
Q
Elimination of cephalosporin?
A
- Primarily renal (dose reduciton in renal disease)
- Ceftriaxone is the exception
- 33-67% excreted unchanged and sig hepatic metabolism
- longest E1/2 T of 3rd generation
- 33-67% excreted unchanged and sig hepatic metabolism
- Routes of admin
- 1st and 2nd both have IV and oral
- Broadest spectrum cephalosporin are generally administered IV
33
Q
Use for Cefazolin?
Anaphylaxis? Allergic reaction? Cross reactivity?
Excretion?
A
- Very common for SSI prophylaxis (CV, ortho, biliary, pelvic, intraabdominal)
- Allergy incidence is 1-10%
- life threatening anaphylaxis -.02%
- laryngeal edema, bronchoconstriciton, severe hypotension<– main, first sign
- get out of beta lactams if anaphylaxis!
- Cross reactivity with other cephalosporins
- PCN and cephalosporin cross reactivity only 1% (but when it happens, it’s life threatening!)
- Renal excretion
34
Q
Adverse effects cephalosporin?
A
- Hypersensitivity: cross reactivity in pt with PCN allergy
- Bleeding
- cefoperazone, cefotetan, cetraixone
- inhibits conversion of Vit K to active form
- typically see this on chronic use
- cefoperazone, cefotetan, cetraixone
- Thrombophlebitis (IV site)
- Hemolytic anemia (rare)
- Superinfection (c diff)
35
Q
Drug interactions for cephalosporins?
A
- Probenecid (prolong DOA by delaying elimination)
- Alcohol- disulfiram like reaction
- inhibit aldehyde dehydrogenase- acetyl aldehyde build up in blood makes people feel awful
- Anticoagulants/ anti PLT drugs with cefoperazone, cefetetan, ceftriaxone
- Calcium and ceftraixone= FATAL precipitates
focus on cephalosporins!
