Antimicrobials Flashcards
1
Q
beta lactam abx
A
penicillins
cephalsporins
carbapenems
2
Q
Risk for SSI: surgical risk
A
procedure type
skill of surgeon
use of foreign material or implantable device
degree of tissue trauma
3
Q
Risk for SSI: patient risks
A
diabetes - vascular disease smoking use - dramatic decrease in SSI if cessation 4-8 wks prior obesity malnutrition systemic steroid use (not proven) immunosuppressive therapy intraoperative hypothermia trauma prothetic heart valves extremes of age hair removal - dont shave preop hospitalization
4
Q
Anesthesia provider can make an impact on SSI prevention though:
A
timely and appropriate use of ABX
maintenance of normothermia
proper syringe/med admin practices
periop glucose control
5
Q
Hypothermia is associated with:
A
increased blood loss - coagulation cascade doesn't work as well increased transfusion req prolonged pacu stay post op pain impaired immune function
compromised neutrophil function –> vasoconstriction –> tissue hypoxia and increased incidence of SSI
6
Q
Microbial resistance to anti-microbials: mechanisms
A
- increase active transport (of ABX) out of bacteria and/or decrease active transport (of ABX) into the cell
- structural changes in drug target (mutations)
- production of a drug ABX antagonist
- enzymatic drug destruction (beta lactamase)
- the more ABX are used the more resistance develops (in target bacteria and normal flora)
- ABX are used extensively in hospitals
7
Q
Antimicrobials and Anesthesiology: Goals and General Rules
A
- inhibit microorganisms at conc that are tolerated by the host (don’t want to give so much that we cause 1) end organ toxicity 2) unacceptable SE)
- MIC = minimum conc that we need to keep infection at bay –> allow its immune system to do its thing
- seriously ill/immunocompromised select bactericidal
- narrow spectrum before broad spectrum or combination therapy to preserve normal flora
8
Q
beta lactams: MOA
A
WEAKEN BACTERIAL CELL WALL
–bind to penicillin binding proteins (only expressed during bacterial proliferation)
- activate autolysins (decrease inhibition of muerin hydrolase - enzymatic destruction of cell wall)
- inhibit (transpeptidases) enzyme needed for cell wall synthesis and integrity (of cross bridges)
9
Q
Penicillin binding protein
A
required for entry of ABX into cell
10
Q
beta lactamase
A
enzyme that will destroy beta lactam ring - could make an ABX uselss for targeting that bacteria
11
Q
Patients with documented IgE mediated anaphylactic reactions the beta lactam ABX can be substituted with?
A
clindamycin or vancomycin
12
Q
Principle concern of Penicillin
A
Allergic reactions - most common cause of drug allergy (incidence 1-10%)
Anaphylaxis (.004 - .04% with 10% mortality)
13
Q
Penicillin: Excretion
A
Rapid renal excretion - plasma conc decreases 50% in 1st hour (short half life)
anuria increases elimination half time by 10 fold
DOSE ADJUST IN RF
14
Q
Administration of probenicid with Penicillin.
A
admin of penicillin with probenicid will reduce renal excretion and prolong action
15
Q
Broad spectrum penicillin: second generation
A
amoxicillin
ampicillin
16
Q
Ampicillin excretion
A
50% excreted unchanged by the kidney 6 hours after admin
17
Q
Carbenicillin: effects and anesthesia considerations
A
broad spectrum penicillin: 3rd generation
E1/2time: 1 hour (2 hrs renal disease) 85% excreted unchanged by kidney high sodium load -- CAUTION IN HF hypokalemia metabolic alkalsosis prolonged bleeding despite normal platelet count
ANESTHESIA CONSIDERATIONS
Preoperative:
lower threshold for BMP, ABG, platelets/CBC, more aggressive about blood availability
18
Q
beta lactamase resistant penicillins: agents and use
A
nafcillin
–penetrates CNS; 80% secreted in the bile/GOOD FOR PATIENTS WITH RENAL DYSFUNCTION
dicloxacillin
oxacillin
19
Q
beta lactamase resistant penicillins: MOA
A
binds irreversibly to b lactamase enzymes
-large side group sterically hinders beta lactamase from cleaving beta lactam ring
20
Q
beta lactam/beta lactamse inhibitor combinations: agents and spectrum
A
unasyn (ampicillin/sulbactam)
augmentin (amoxicillin/clavulanic acid)
timentin (ticarcillin/clavulanic acid)
zosyn (pip/taz)
broadest spectrum agents
- gram positive
- gram negative activity
- anerobes
21
Q
Cephalosporins: MOA, therapeutic index
A
favorable therapeutic index (low toxicity, highly effective)
WEAKEN BACTERIAL CELL WALL
–bind to penicillin binding proteins (only expressed during bacterial proliferation)
- activate autolysins (decrease inhibition of muerin hydrolase - enzymatic destruction of cell wall)
- inhibit (transpeptidases) enzyme needed for cell wall synthesis and integrity (of cross bridges)
22
Q
Cephalosporins and beta lactamase susceptibility through generations
A
b lactamase susceptibility decrases as you move from 1st to 4th gen
23
Q
cephalosporins and gram activity through generations
A
1st and 2nd gen: gram pos activity, don’t cross BBB, not active against gram neg
3rd and 4th gen: quite broad, gram neg activity & activity against anaerobes & ability to penetrate the BBB
24
Q
Broadest cephalosporin
A
4th generation cephalosporin: cefepime
25
Ceftaroline
5th (or 3rd) generation cephalosporin
MRSA COVERAGE
26
Cephalosporins: Elimination + exception to rule
primarily renal (DOSE REDUCTION IN RENAL DISEASE)
exception: ceftriaxone - sig hepatic metabolism, also, longest E 1/2 of 3rd gen
27
Cefazolin: Cautions/CI
crosses the placenta
allergy incidence 1-10%
cross reactivity with other cephalosporins
Penicillin/cephalosporin cross reactivity: 1%
RENAL EXCRETION
28
Cephalosporins: Adverse Effects
- bleeding (cefoperazone, cefotetan, ceftriaxone)
- --inhibit conversion of vitamin K to active form
- --CHECK PT/INR
- thrombophlebitis (IV site) - uncommon
- hemolytic anemia - very rare
- superinfection (c diff) - risk the more broader spectrum you go
29
Cephalosporins: Drug Interactions
-probenacid (prolong DOA by delaying elimination)
- ETOH (cefazolin, cefmetazole, cefoperazone, cefotetan)
- -disulfiram like reaction
-anticoagulants/anti-plt dugs (cefoperzone, cefotetan, ceftriaxone)
- calcium + cefitriaxone: fatal precipitates --> NO LR
- --especially with neonates
30
Ceftriaxone considerations
- sig hepatic metabolism
- 33-67% excreted unchanged in urine
- longest E1/2t of 3rd gen
```
bleeding risk (prevents active form of vit K)
DI with anticoag/anti-platelet
```
fatal precipitates with calcium (NO LR)
31
Azetreonam (Azactam): Class and MOA
Monobactam
Cell wall agent
- inhibits cell wall synthesis = cell lysis and death
- has a high affinity to a specific PBP (PBP3) in gram neg bac only
**highly resistant to beta lactimases**
32
Azetreonam (Azactam): SE profile, PK
few adverse effects
Excreted unchanged by kidney
E1/2t: 1.5 hours
most sig risk: GI superinfections
33
Good substitute for patient with a penicillin allergy
Azactam - cross reactivity is unlikely
34
Macrolides: MOA and agents
MOA: bind to a 50S subunit of the ribosome to block protein synthesis in bacterial cells - bacteriostatic
- erythromycin
- clarithromycin/biaxin
- azithromycin/zithromax
35
ABX coverage against atypical pathogens.
MACROLIDES
```
community acquired PNA
legionella pneumophilia (legionnaire's disease)
pertussis
acute diptheria
chlamydial infections
bacterial endocarditis
```
36
Macrolides: Side Effects
- GI intolerance - most common side effect
- severe N/V can occur with infusion
- may slow gastric emptying - inc asp risk
- cholestatic hepatitis
- IV formulation associated with tinnitus and hearing loss
- thrombophlebitis
37
Macrolides: metabolism
metabolized by CYP3A4 - can inc serum conc of:
- theophylline
- warfarin
- cyclosporine
- methylprednisone
- digoxin
excreted mostly in bile --> GOOD FOR RENAL DISEASE (no need to alter dose in renal disease)
38
Macrolides: QT effects
PROLONGS QT - prolongs cardiac repolarization
reports of torsades
CYP3A4 inhibitors can inc plasma concentrations and increase risk of fatal vent dysrhythmias
- -verapamil
- -diltiazem
- -protease inhibitors
- -azole antifungals
5x inc in sudden cardiac death when ERYTHROMYCIN and CYP3A4 inhibitor are prescribed together
39
Clindamycin: Class and MOA
Linomycin
MOA: blocks protein synthesis by binding to 50S ribosomal subunit - usually bacteriostatic
similar to erythromycin in antimicrobial activity, but more active with anaerobes
commonly used in female GU
40
Clindamycin: adverse effects AND anesthesia considerations
- pseudomembranous colitis --> severe diarrhea should indicate d/c of therapy - CONSIDER FLUID/ELEC BALANCE
- skin rash/hypersensitivity
- blood dyscrasias (eosinophilia, leukopenia, thrombocytopenia - LOWER THRESHOLD FOR GETTING CBC
- PROLONGED PRE AND POST JUNCTIONAL EFFECTS AT NMJ IN THE ABSENCE OF NDMR
- -concurrent admin with NDMR can produce long lasting, profound NMB
- -not antagonized with anticholinesterases or calcium!
41
Clindamycin: metabolism
Only 10% excreted unchanged in urine
DOSE DECREASE IN LIVER DISEASE
42
Vancomycin: Class and MOA
Glycopeptide
MOA:
- inhibits bacterial cell wall synthesis = cell lysis and death
- binds and inactivates cell wall precursors
- bactericidal - "slowly cidal"
43
Vanc: uses
- synergistic with aminoglycosides - vanc increases access of aminoglycosides to actual site of action (aminoglycosides inhibit 30S subunit of ribosome)
- activity against MRSA
- good choice in severe PCN allergy patients
44
Vanc: Dosing
10-15 mg/kg SLOWLY over 60 minutes
1 gram mixed in 250 ml
(fast admin carries risk of "red man syndrome" --> profound hypotension)
*12 hours of therapeutic plasma conc**
DOSE ADJUST FOR RENAL INSUFFICIENCY
45
Vanc: metabolism/excretion
DOSE ADJSUT FOR RENAL INSUFFICIENCY
renal excretion: 90% unchanged in urine
E1/2t: 6 hours (can be prolonged up to 9 days with RF)
poor PO absorption (exception: PO for intestinal infection)
46
Vanc: drug interactions
other nephrotoxic drugs
- dye
- NSAIDs
- toradol
- ampho b
- cyclosporine
synergistic nephrotoxicity with aminoglycosides
47
Vanc: side effects
- thrombophlebitis (irritating to tissue)
- nephrotoxicity (renal failure) - rare unless coadmin with other nephrotoxic drugs
- ototoxicity with conc > 30 mcg/ml (increased risk if coadmin with aminoglycosides)
- hypersensitivity (macropapular skin rash)
- "Red man syndrome" -- severe hypotension (flushing due to histamine release) if give IV in < 30 min
- --intense facial and truncal erythema from histamine release
--diphenhydramine 1 mg/kg and cimetidine 4mg/kg 1 hour before induction limits histamine related effects
-immune mediated thrombocytopenia and bleeding - rare
48
Vanc: anesthetic preop lab considerations
creatinine - narrow therapeutic index
| CBC - thrombocytopenia SE rare
49
Aminioglycosides: MOA
Work on 30S ribosomal subunit
-block the initiation of protein synthesis/premature termination of protein synthesis/abnormal protein formation in bacterial cells
effective in mycobacterium TB
50
Aminoglycosides: metabolism and elimination
- really positively charged, highly water soluble - Vd = extracellular volume
- extensive renal excretion through glomerular filtration (almost 100%)
E1/2t: 2-3 hrs (inc 20-40 fold in RF)
51
Aminoglycosides: side effects
- limited by their toxicity
- cross the placenta and could cause harm (oto and nephrotoxicity in babe)
- ototoxicity (tend to conc around ear)
- ---esp with diuretics, furosemide, mannitol
- nephrotoxicity (tend to conc in kidney)
- ---esp with ampho b, cyclosporine, etacrynic acid, vanco, NSAIDs, ketorolac
SKELETAL MUSCLE WEAKNESS: inhibit pre junctional release of ach and decreases post synaptic sens to the neurotransmitter - consider MG pts
--profound blockade with NDNMB
52
Amikacin: drug interaction
Aminoglycoside
do not use with penicillin (may antagonize PCN effects)
LITTLE KNOWN ANTIBIOTIC RESISTANCE
53
Gentamicin: Class and toxic level
Aminoglycoside
>9 mcg/ml
54
Aminoglycosides and NDMR
IV admin of aminoglycosides associated with potentiation of NDNMB
paralysis usually reversible with calcium gluconate or neostigmine
55
Linezolid (Zyvox): MOA and use
MOA: works on 23S subunit
inhibits bacterial protein synthesis by preventing the formation of a functional ribosomal subunit initiation complex that is essential for the bacterial translation process
*can't translate mRNA into protein*
very important because its resistant to MRSA and VRE
56
Linezolid (Zyvox): Adverse effects and anesthetic implications
- thrombocytopenia, anemia, leukopenia, pancytopenia (esp > 2 wks of TX)
- ----CBC CHECK
- GI effects
- ----MORE AGGRESSIVE ANTIEMETIC PLAN + FLUID/ELEC BALANCE
- RARE: optic and peripheral neuropathy
- ---POSITIONING (think prone), NEURAXIAL ANESTHESIA
- formulated w/ phenylalanine
- ---avoid in pts with phenylketonuria
- weak MAOI: watch for additive NE and 5HT effects when used with other sertonergic agents and/or indirect sympathomimetics --> risk of serotonin sydrome & hypertensive crisis
- ---EPHEDRINE AND SSRIS CONTRAINDICATED
57
Fluoroquinolones: MOA + use + agents
MOA: inhibits DNA gyrase and topoisomerase, which are critical bacterial enzymes used in DNA replication & cell division --> stop growth and proliferation of bacteria
Use: complicated GI and GU infections, respiratory tract, TB, anthrax
ciprofloxacin (cipro)
levofloxacin (levaquin)
moxifloxacin (avelox) - higher risk of adverse effects
58
Fluoroquinolones: Adverse effects
- class warning for QT PROLONGATION
- nausea
- CNS disturbances
- opportunistic candida
- rashes
- photo-toxicity (severe sunburn)
- muscle weakness in MG pts
- tendinitis and achilles tendon rupture due to extracellular cartilage matrix weakening
- -highest risk > 65 yo, corticosteroid use, s/p transplant
- -avoid IV form <18 yo - rare, but still growing
59
Fluoroquinolones: drug interactions
CYP450 interactions, increases levels of:
theophylline
warfarin
tinidazole
60
Fluoroquinolones: Elimination
renal excretion through glomerular filtration and renal tubular secretion
--DECREASE DOSE IN RENAL DYSFUNCTION
E1/2t: 3-8 hours (pretty long)
61
Sulfonamides (Bactrim, specifically): MOA and uses
MOA: prevent normal use of PABA by bacteria to synthesize folic acid; inhibit microbial synthesis of folate production
*folic acid needed for nucleotide synthesis*
Uses: UTIs, burns, inflammatory bowel disease
sulfamethoxazole and trimethoprim used synergistically because they effect different parts of biosynthetic pathway
62
Bactrim: side effects
- skin rash to anaphylaxis
- photosensitivity
- allergic nephritis
- drug fever
- hepatotoxicity
- acute hemolytic anemia
- thrombocytopenia
- increase effect of PO anticoagulant
63
Bactrim: metabolism and elimination
liver and kidney
portion of drug is acetylated in the liver and other is renally excreted
renal disease - DOSE REDUCTION
64
Metronidazole: Use
**rec for pre op prophylaxis for CRS**
variety of infections: CNS, abdominal and pelvic sepsis, pseudomembranous colitis (c diff), endocarditis
well absorbed orally and widely distributed in tissue including CNS
65
Metronidazole: side effects
- dry mouth
- metallic taste
- nausea
- avoid alcohol - disulfuram reaction
- RARE: neuropathy and pancreatitis
66
Isoniazid: anesthetic considerations
antimycobacterial agent - 1st line agent against TB
hepato - renal toxicity -- PRE OP WORK UP
67
Rifampicin: anesthetic considerations
antimycobacterial agent - 1st line agent against TB
hepatic enzyme induction -- MAY HAVE TO DOSE ANESTHETIC DRUGS MORE FREQUENTLY
hepato - renal toxicity, thrombocytopenia, anemia - PREOP WORK UP (consider patient type and surgery type. Is this a pt with low O2 carrying capacity or CAD --> at risk for MI)
68
Ethambutol: anesthetic considerations
antimycobacterial agent - 1st line agent against TB
optic neuritis - POSITIONING, HTN
69
Pyrazinamide: anesthetic considerations
antimycobacterial agent - 1st line agent against TB
Liver toxicity - PRE OP WORK
70
Amphotericin B: Class and MOA
Antifungal
MOA: binds to ergosterol (analagous to cholesterol, but not actually cholesterol) in fungal membranes to form pores --> altered membrane permeability causes leakage of cellular contents
71
Amphotericin B: Elimination
Slow renal excretion
renal fxn impaired in 80% of pts treated with this drug - most recover after drug is stopped but some resulting permanent decrease in GFR may remain
MONITOR SERUM CREATININE
72
Ampho B: side effects and anesthetic considerations
- fever, chills, dyspnea, hypotension can occur during infusion
- impaired hepatic function
- hypokalemia - ELECTROLYTES
- allergic reactions
- seizure
- anemia - CBC
- thrombocytopenia - CBC
ANESTHETIC CONSDIERATIONS:
- careful of anything that could be nephrotoxic
- CBC
- FLUID LOAD
- ELECTROLYTES
73
Viral life cycle
1. absorption
2. penetration
3. uncoating
4. viral genome replication (DNA or RNA)
- -using host or viral polymerases
5. maturation
6. release
74
Acyclovir: Class + MOA
Pro - drug activated by viral phophorylation by THYMIDINE KINASE
MOA: inhibits viral DNA synthesis
- inhibition of DNA polymerase
- insertion into viral DNA blocking the addition of subsequent nucleotides (block strand growth)
75
Acyclovir: Uses
HSV >>>> VZV >>>> CMV >>>> mammalian
Uses: genital &herpes labialis, chicken pox (only if given within 24 hrs onset), shingles (high doses), and herpes encephalitis
CMV, EBV NOT SENSITIVE
76
Acyclovir: PK
poor oral availability <20%
great distribution (CSF - 50% plasma conc)
Renal elimination: unchanged - DOSE REDUCE IN RF
E1/2T: 2.5 hours
77
Acyclovir and pregnancy
SAFE IN PREGNANCY/BREASTFEEDING
78
Acyclovir: adverse reactions
- phlebitis (IV)
- nephrotoxicity (IV/PO) - give over > 1 hour, HYDRATION IS IMPORTANT
- neurotoxicity (IV); rare excitatory reactions, hallucinations, myoclonus, esp renal disease (RESEMBLES KETAMINE)
- GI intolerance
79
Ganciclovir: Precautions
mutagenic and carcinogenic!!!!!
80
Ganciclovir: MOA and use
pro - drug: phosphorylated by CMV within cells; active triphosphate form inhibits viral DNA synthesis (inhibits DNA polymerase & incorporated into growing chain = premature chain termination)
Uses: CMV, pneumonitis, colitis, viremia, prophylaxis
81
Ganciclovir: adverse effects
- granulocytopenia (40%)
- thrombocytopenia (20 %)
- serum creatinine
- --monitor levels and stop if absolute neutrophil ct or plt ct drop significantly
MONITOR CBC AND CREATININE
82
Interferon A: use and MOA
Use: Hep C
interferons are signaling proteins made and released by host cells in response to viruses
blocks viral cell entry, decreases synthesis, of viral mRNA & proteins, vial assembly and release
83
Interferon A: adverse effects and anes. considerations
- flu like symptoms (PT MAY BE TAKING NSAIDS FOR SYMPTOMS AND THEY CAN'T BE TAKING THESE PRIOR TO SX SO THEY MAY FEEL KIND OF MISERABLE)
- neuropsychiatric effects, esp depression
- fatigue, thyroid dysfunction, heart damage (LOWER THRESHOLD FOR CV WORKUP, THYROID LABS)
- bone marrow suppression (neutropenia, thrombocytopenia, may induce autoimmune disease) - (PRE OP CBC)
84
Protease Inhibitors: Use and MOA
Tx of chronic hep c by inhibition of viral protease required for viral replication
85
Protease Inhibitors: Adverse effects and anes. considerations
- hepatoxicity (PRE OP LIVER LABS)
- photosensitivity (severe sunburn)
- severe rash (PRE OP SKIN ASSESSMENT)
- contains sulfonamides (NO SULFA ALLERGY)
86
Protease Inhibitors: drug interactions
- amio (severe bradycardia)
- reduce statin doses
- inc benzo levels
87
Protease Inhibitors: Metabolism and Elimination
Metabolized by CYP3A4 (drug interactions)
| 91% excreted in feces
88
NS5A inhibitors (daclatasvir): drug interaction
metabolized by CYP3A4 - CAUTION WITH AMIODARONE - SEVERE BRADYCARDIA
89
NS5A inhibitor (daclatasvir): MOA and use
Hep C
inhibit NS5A, a protein required for HCV RNA replication and assembly
90
NS5B inhibitor (NPI): adverse effects
adverse effects as a result of combo therapy
- nausea
- HA
- anemia
- insomnia
91
NS5B inhibitor (NPI): drug interaction
amiodarone - severe bradycardia
92
Nucleoside reverse transcriptase inhibitors (NRTIs): adverse effects
- Nausea
- diarrhea
- myalgia
- increased LFTs
- peripheral neuropathy
- renal toxicity
- marrow suppression
- anemia
- lactic acidosis
93
NRTIs: drug interaction
VERY POWERFUL INHIBITION OF CYP450
| -zidovudine + corticosteroids can = severe myopathy including resp muscle dysfunction
94
Protease Inhibitors (PI), ritonavir: adverse effects
- hyperlipidemia
- glucose tolerance
- abnormal fat distribution
- altered LFTs
- inhibition of cyp 450 3A4
95
Protease inhibitors: drug interactions
INHIBITION OF CYP 3A4
| --decreased fentanyl clearance ~67% (lower dose)
96
Nonnucleoside analog reverse transcriptase inhibitors (delavirdine AND nevirapine): drug interactions
Delavirdine - INHIBITS CYP 450
- - inc concentrations of:
- ---sedatives
- ---antiarrhythmics
- ---warfarin
- ---calcium channel blockers
Nevirapine - induces CYP 450 by 98%!!
97
Integrase strand transfer inhibitors (ISTIs): effects
appear well tolerated
new agents
may have unknown SE
98
chemokine receptor 5 antagonists and entry inhibitors: effects
appear well tolerated
newer
may have unknown SE
99
chemokine receptor 5 antagonists and entry inhibitors: drug interactions
appears to interact with midazolam altering clearance and drug effect
100
Ritonavir (protease inhibitor): interactions with midaz
increased effects, lower dose
101
Ritonavir (protease inhibitor): interactions with fentanyl
increased effects, lower dose
102
Ritonavir (protease inhibitor): drugs to avoid
PRONOUNCED EFFECTS: LIFE THREATENING
- meperidine
- amiodarone (arrhythmias)
- diazepam
103
Parturient and antimicrobials: considerations
-most antimicrobials cross the placenta and enter maternal milk
-plasma concentrations could be 10-50% lower than predicted
--increased maternal blood volume, GFR, metabolism
(MAY NEED TO INCREASE DOSE, MAY BE METABOLIZED AND CLEARED FASTER)
-teratogenicity
104
Elderly and antimicrobials: considerations
- renal impairment
- decreased plasma protein
- reduced gastric motility and acidity
- --altered distribution: increased total body fat
- --decreased plasma albumin concentration
- --decreased hepatic blood flow
- --decreased GFR
105
Pregnancy and antimicrobials: SAFE
- penicillins
- cephalosporins
- erythromycin
106
Pregnancy and antimicrobials: CAUTIOUS
-aminoglycosides (ototoxicity in mom and baby)
107
Pregnancy and antimicrobials: CONTRAINDICATED
- flagyl
- tetracyclines
- fluoroquinolones
- trimethoprim
108
Elderly and antimicrobials: SAFE
safe if normal serum creatinine concentration
- penicillins
- cephalosporins
109
Elderly and antimicrobials: CAUTION
aminoglycosides and vancomycin may require adjustments in dose
