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Micro Exam 1 > Pogue: Antimicrobials I > Flashcards

Pogue: Antimicrobials I Flashcards

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1
Q

Clinically important bacteria

G+

A

o Streptococcus spp.
o S. aureus
o Enterococcus spp.

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2
Q

Clinically important bacteria
G-

Enteric (3):

A

Proteus spp.
E.coli
K.pneumoniae)

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3
Q

Clinically important bacteria
G-

Sneaky gram negatives (SPICE)

A

Sneaky gram negatives (SPICE)

Serratia
Providencia
Indole (+) proteus
Citrobacter
Enterobacter
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4
Q

Clinically important bacteria
G-

Nasty gram negatives(2):

A

Nasty gram negatives

  • P. aeruginosa
  • A. baumannii
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5
Q

Clinically important bacteria

Anaerobes:

A

C.difficile

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6
Q

Empiric vs definitive therapy

A

Empiric Therapy: therapy before the causative organism is known; based off of most common pathogens

Definitive Therapy: once cultures and sensitivities are known

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7
Q

Bacteriocidal vs bacteriostatic

A

Bacteriocidal: an antibiotic makes the number of bacteria decrease

Bacteriostatic: the number of bacteria stays the same upon exposure to an antibiotic

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8
Q

Synergy:

A

1 + 1= more than 2 (ie. adding 2 drugs together has synergistic effects that make the combination better than the sum of its parts)

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9
Q

Pharmacokinetics and Pharmacodynamics

A
  • Pharmacokinetics: what the body does to the drug (absorption, distribution, metabolism, excretion)
  • Pharmacodynamics: what the drug does to the body (concentration-dependent vs. time-dependent killing)
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10
Q

Minimal inhibitory concentration (MIC)

A

The lowest concentration of the antimicrobial that inhibits growth (bacteriostatic effect) in the test tube

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11
Q

Drugs that affect cell wall synthesis:

A

B-lactams, Vancomycin

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12
Q

Drugs that affect bacterial DNA replication

A

Fluroquinolones

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13
Q

Drugs that act as folic acid inhibitors

A

Trimethoprim (Stops DHF A –>THF A)

Sulfonamide (Stops PABA –> DHF A)

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14
Q

Drugs that affect the cell membrane

A

Daptomycin

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15
Q

Protein synthesis inhibitors

50s
30s

A 
50s
Macrolides
Lincosamides
Linezolid
Streptogramins

30s
Aminoglycosides
Tetracyclines

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16
Q

Mechanisms of Resistance (3):

A

Antimicrobial Modifying Enzymes: an example is beta-lactamases

Target Site Alterations: an example is penicillin binding protein alterations

Decreased Concentrations in a Cell:
o Efflux pumps: pump drug out
o Outer membrane porin downregulation: less drug gets into the cell

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17
Q

BETA-LACTAMS:
General:
Bacteriocidal:
Time-Dependent Antimicrobials:

A

BETA-LACTAMS:
• General:
- Most commonly used antimicrobials
- First available in the 1940s (penicillin)

Bacteriocidal: leads to rapid cell death

Time-Dependent Antimicrobials: higher doses rarely the answer in treatment

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18
Q

BETA-LACTAMS

MOA:

A

Mechanism of Action:
Inhibition of the final step of cell wall synthesis

Blocks the cross-linking of peptidoglycan (essential for structural integrity)

Process normally carried out by enzymes called penicillin-binding protins (PBPs)

Beta-lactams bind PBPs and block transpeptidation
- Not lethal itself, but part of process that will lead to rapid cell death

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19
Q

BETA-LACTAMS
Elimination:
Exceptions:

A

Renal Dosing:

Nearly every beta-lactam is eliminated renally and requires renal dosing adjustment

Exceptions:
o Ceftriaxone
o Penicillinase-resistant penicillins (Nafcillin, Oxacillin, Methicillin, Dicloxacillin)

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20
Q

Penicillin

Spectrum of Activity (5):

A 
o	Streptococci (S.pyogenes, S.viridans)
o	Enterococci (E.faecalis)
o	Treponema pallidum
o	Clostridium spp. (not C.difficile)
o	Other mouth anaerobes
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21
Q

Beta-Lactamases:

A

Enzymes that are secreted by the organism that hydrolyze beta-lactam antibiotics

Likely evolved from PBPs

B-lactamases that only hydrolyze penicillin are called penicillinases

Initially, penicillin was DOC for S.aureus but it has created penicillinases making them resistant
- Now only 5-10% susceptable

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22
Q

Benzathine Penicillin:

Use:

A

Long acting depot preparation that must be given IM

Only used to treat extremely susceptible bugs (Treponema pallidum¸ which causes syphilis, is a classic example)

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23
Q

Current Use of Penicillin (4):

A

Syphilis

Dental coverage (Mouth anaerobes)

Necrotizing Faciitis (S.pyogenes)

Definitive therapy for streptococcal infections

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24
Q

Penicillinase-Resistant Penicillins/”Anti-Staphylococcal Penicillins”:

A

Nafcillin - Commonly used
Methicillin - Not clinically used
Oxacillin - Commonly used
Dicloxacillin - Oral

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25
Penicillinase-Resistant Penicillins: Designed to overcome: DOC for: Strep activity? Lacks:
``` - IN GENERAL: o Designed to overcome penicillinase o DOC for MSSA o Some streptococcal activity o Lacks gram negative and enterococcus activity ```
26
MRSA (Methicillin Resistant Staph Aureus):
Results from PBP2A alteration, in which the PBP has a decreased affinity for beta-lactams and can still cross-link in their presence Such a decrease in affinity leads to resistance against ALL beta-lactams**
27
Aminopenicillins:
Ampicillin (IV) Amoxicillin (PO) - Better absorption
28
Aminopenicillins | HELPS bugs:
H.infleunzae E.faecalis L.monocytogenes P.mirabalis Samonella and Shigella spp.
29
Aminopenicillins Clinical use: Only static against: Used with what for synergy against serious enterococcus infection? Meningitis:
Enterococcal Infections: static against E.faecalis; minimal activity against E.faecium Use with gentamicin for synergy in serious infections Meningitis: when concern for listeria, use high dose ampicillin - Amoxicillin (PO): o Better absorption (hence PO formulation) o Same clinical use as ampicillin
30
Piperacillin Expands coverage of ampicillin to include: How does enterococcus susceptibility compare to ampicillin? Piperacillin/tazobactam:
Expands coverage of ampicillin to include P.aeruginosa IV only If enterococcus susceptible to ampicillin, its susceptible to piperacillin Piperacillin/tazobactam has no advantage over piperacillin alone for treatment of P.aeruginosa No longer commercially available*
31
Beta-lactam/beta-lactamase inhibitor combinations | Basics:
o Better aerobic gram negative and anaerobic coverage (typically have beta-lactamases) o Can treat MSSA
32
Beta-lactam/beta-lactamase inhibitor combinations (4):
Amoxicillin/Clavulanic Acid (Augmentin) –PO Ampicillin/sulbactam (Unasyn) –IV Ticaracillin/clavulanic acid (Timentin) –IV Piperacillin/Tazobactam (Zosyn) –IV
33
What is ticarcillin? Why teach us ticarcillin/clavulanic acid?
Similar class to piperacillin-however, not clinically use Because of the clavulanic acid it has activity versus S.maltophilia (Nosocomial pathogen)
34
Amoxicillin/Clauvulanic Acid
(Augmentin) | Empiric regimens for broad coverage for community based pathogens (diabetic foot ulcers, intra-abdominal infections)
35
Ampicillin/Sulbactam What does sulbactam have antimicrobial activity against?
(Unasyn) Empiric regimens for broad coverage for community based pathogens (diabetic foot ulcers, intra-abdominal infections) Sulbactam itself can be antimicrobial: activity against A.baumannii (makes Unasyn the DOC. Ampicillin is along for the ride.)
36
Piperacillin /Tazobactam (Zosyn)
Empiric broad spectrum for nosocomial infections (because it can treat pseudomonas)
37
What is the DOC against A. baumannii?
Ampicillin/Sulbactam (Unasyn)
38
Common Adverse Effects of Penicillins (6):
Allergic Reactions Acute Interstitial Nephritis Bone Marrow Suppression Seizures GI Effects Contact Dermatitis
39
Penicillin allergy
Rash --> Anaphylaxis | - Related to beta-lactam ring or side chains? (important to make distinction to determine cross-reactivity)
40
Acute Interstitial Nephritis ``` Most common with: Triad of symptoms: Starts off as: Progresses to: What's seen on biopsy? ```
Most common with methicillin (but can be seen with all) Fever, rash, eosinophilia Starts as non-oliguric renal failure, but can progress to anuria and renal failure Eosinophilic cells with tubular damage seen on biopsy
41
Common Adverse Effects of Penicillins | Seizures associated with:
Associated with high doses and non-renally adjusted doses
42
Common Adverse Effects of Penicillins | Most common with ampicillin:
GI Effects | Contact Dermatitis
43
Penicillin Drug Interactions: What drug for gout can block renal excretion and increase the half-life of penicillins?
Minimal: Potential for additive toxicities with other agents (rarely seen) Probenecid: drug for gout that can block renal excretion and increase the half-life of penicillins o Can be used clinically to increase drug concentrations
44
CEPHALOSPORINS: ``` Class: Structure: MOA: G+/- Coverage: Activity against enterococcus: ```
Beta lactam Structure: similar to penicillins (6 membered ring attached to beta-lactam ring instead of 5 membered ring) MOA: same as penicillin Good Gram positive coverage ENTIRE CLASS lacks activity against enterococcus (G+)
45
What are the subclasses of beta-lactams? (wiki)
penicillin derivatives (penams) cephalosporins (cephems) monobactams carbapenems
46
``` First Generation Cephalosporin Activity against: G+ G- Anaerobes P.Aeruginosa ```
Gram (+) Activity: Good vs. staphylococcus (MSSA) Good vs. most streptococcus (S.pneumoniae variable) Good skin coverage as long as MRSA is not a concern Gram (-) Activity: POOR Some activity against PEK organisms (Proteus, E.coli, K.pneumoniae) Anaerobic/P.Aeruginosa Activity: NONE
47
First Generation Cephalosporin | First Generation Agents (3):
o Cephalexin o Cefazolin o Cefadroxil
48
Second Generation Cephalosporin agents:
Cefaclor, cefuroxime (2A) | Cefotetan, cefoxitin (2B) “cephamycins”
49
Cefaclor and Cefuroxime (2A): ``` Activity against: G+ G- Anaerobes P.Aeruginosa Clinical Use: ```
Gram (+) Activity: improved against S.pneumoniae Gram (-) Activity: a little better Anaerobic/P.Aeruginosa Activity: NONE Clinical Use: Respiratory tract infections (S.pneumo, H.flu, M.cattarhalis)
50
Cefotetan and Cefoxitin (2B; “Cephamycins”): ``` Activity against: G+ G- Anaerobes P. aeruginosa Clinical Use: ```
Gram (+) Activity: improved against S.pneumoniae Gram (-) Activity: a little better Anaerobic Activity: EXCELLENT P.aeruginosa Activity: NONE Clinical Use: - Community acquired intra-abdominal infections (community acquired Gram (-) more likely to be susceptible) - Surgical prophylaxis
51
Which type of cephalosporin has the best activity against anaerobes?
Cefotetan and Cefoxitin (2B; “Cephamycins”)
52
Third Generation Cephalosporin agents (4):
Cefotaxime Ceftriaxone (IV): Cefixime Cefpodoxime (PO)
53
Third Generation Cephalosporin ``` Activity against: G+ G- Anaerobes P. aeruginosa Use caution with: ```
Gram (+) Activity: excellent S.pneumoniae coverage; variable MSSA Gram (-) Activity: excellent vs. most nosocomial Gram negative bacilli Anaerobic/P.Aeruginosa Activity: NONE **MUST USE CAUTION WITH ENTEROBACTER AND OTHER SPICE DRUGS**
54
Ceftriaxone DOC for: What is it coupled with for intra-abdominal infections? Also used for:
Ceftriaxone DOC for CAP, meningitis (S.pneumo) Intra-abdominal infections (+ metronidazole) Urinary tract infections Oral 3rd generation cephalosporins may be used for respiratory infections when oral therapy indicated
55
Unique 3rd Generation Agent- Ceftazadime ``` Activity against: G+ G- Anaerobes P. aeruginosa Clinical use: ```
Gram (+) Activity: less staphylococcus (MSSA) and streptococcus action Gram (-) Activity: good Anaerobic Activity: NONE P.Aeruginosa Activity: YES Clinical Use: limited due to its propensity to induce resistance mechanisms Nosocomial meningitis (because of pseudomonas activity)
56
S.pneumoniae Mechanisms of resistance to ß-lactams is mediated by: How do 3rd generation cephalosporins overcome this? How are MICs affected? Exceptions:
Mechanisms of resistance to ß-lactams is mediated by small changes to PBPs 3rd generation cephalosporins overcome this by tighter binding to PBP Minimum inhibitory concentrations (MIC) are higher, but can be overcome (this is not the case with second generation) Exception meningitis (because sufficient concentrations would not be seen at the site of action)
57
Meningitis | What is the treatment of choice for CNS infection?
3rd generation cephalosporins are treatment of choice for CNS infections
58
What have excellent penetration into meninges?
Ceftriaxone and ceftazadime (high dose) have excellent penetration into meninges
59
What is standard for community acquired bacterial meningitis?
Ceftriaxone is standard for community acquired bacterial meningitis
60
What is often used for nosocomial organisms? Why?
Ceftazadime often used for nosocomial organisms because it adds pseudomonas
61
``` SPICE organisms: List: What do all of them have? What might happen if treated with 3rd gen cephs? Generally use what to treat? ```
Serratia, providencia, indole (+) proteus, citrobacter, enterobacter All have a ß-lactamase that can be selected for Initially the lab says susceptible to 3rd gen cephs –If treated with 3rd gen cephs the b-lactamase is selected for which confers resistance, and the patient may get worse Take home-use with extreme caution in these organisms in severe infections –Generally use cefepime or carbapenems
62
4th generation: ``` Activity against: G+ G- P. aeruginosa Use caution with: ```
4th generation: Cefepime Gram (+) –Excellent strep and staph (MSSA) Gram (-) –Great against nosocomial organisms –SPICE organisms, –Questionable activity against Extended spectrum Beta lactamases (ESBL) organisms P.aeruginosa: YES
63
Ceftaroline: MOA: G+ G- Clinical use
Ceftaroline (“Fifth Generation Cephalosporin”): MOA: binds PBP2A and PBP2X Gram (+) Activity: can be used for MRSA; better S.pneumo coverage; activity against E.faecalis Gram (-) Activity: Between 2nd and 3rd generation cephalosporins Clinical Use: newer drug; CAP, skin infections?
64
Cephalosporin Side Effects: What does ceftriaxone also cause? Hypothrombinemia and Disulfiram-Like Reactions in Patients Taking Alcohol:
Similar to penicillins Biliary Sludging in Neonates: Ceftriaxone Hypothrombinemia and Disulfiram-Like Reactions in Patients Taking Alcohol: Cefotetan, Cefetazole, Cefoperazone (Cephalosporins with a methythiptetrazole/MTT group)
65
Cephalosporin Cross-Reactivity
5-10% cross reactivity with penicillins However, true cross-reactivity much lower –0-2% –Side-chain vs. ß-lactam –Ceftazadime and aztreonam
66
What are the broadest agents currently available?
Carbapenems
67
CARBAPENEMS G+ G- Anaerobes: Cross-reactivity with penicillins:
Gram (+) Action: good, not great (imi > dori/mero > erta) Gram (-) Action: excellent (dori/mero > imi > erta) Anaerobes Action: excellent (but not C.diff) Cross reactivity with penicillins exists (0-50%), but less likely than in cephalosporins
68
Group 1 Carbapenem Drug Holes: DOC for: Decrease selective pressure on:
Ertapenem More narrow spectrum than group 2 Holes: APE (acinetobacter, pseudomonas, enterococcus) Drug of choice for ESBL producing organisms •Decrease selective pressure on pseudomonas
69
Where are ESBLs most commonly seen? Ability to hydrolyze what? DOC?
ESBL = Extended Spectrum B-Lactamase Most commonly seen in E.coli and K.pneumoniae – Can be transferred to other enterobacteraciae Ability to hydrolyze extended spectrum ß-lactams If present all penicillins, cephalosporins, and aztreonam are considered resistant - Most are also resistant to other agents Carbapenems are the drugs of choice
70
What carbapenems don't cover:
``` - What they do NOT cover: o MRSA o Enterococci resistant to ampicillin o Stenotrophomas maltophilia o KPC o C.difficile o Fungi and viruses ```
71
Group 2 Carbapenems ``` Drugs: G- coverage: ESBL? Pseudomonas aeruginosa? A.baumannii Clinical use: ```
Imipenem, Meropenem, Doripenem Great Gram (-) Coverage: o ESBL o Pseudomonas aeruginosa (including those resistant to cefepime and pip/tazo) o A.baumannii Clinical Use: multi-drug resistant organisms
72
Side Effects of Carbapenems: | What is cilastatin?
SEIZURES Based off of old imipenem data (may have been related to cilastatin, a dihydropeptidase inhibitor added to imipenem to decrease toxicity and increase half life) More likely at a higher dose
73
AZTREONAM What is a monobactam? G+/G- activity: Pseudomonas aeruginosa? ESBL? Clinical use:
It is a monobactam Monobactam: β-lactam compounds wherein the β-lactam ring is alone and not fused to another ring Gram (-) Activity Only: - Includes pseudomonas - NO ESBL ``` Clinical Use: Empiric gram (-) nosocomial coverage in patients with a penicillin allergy (since no cross reactivity) ```
74
What is Acinetobacter Baumannii susceptible to?
Acinetobacter Baumannii and ß-lactams Ampicillin/Sulbactam Carbapenems Often the only two agents this organism is susceptible to - And now frequently resistant to these as well….

Micro Exam 1 (18 decks)

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