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Antibacterials Flashcards

1
Q

Four Mechanisms of Actions of Antibacterials

A
  1. inhibitors of cell wall synthesis
  2. inhibitors of translation and transcription
  3. inhibition of DNA syntheses and integrity
  4. inhibitors of folate synthesis and function
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2
Q

Inhibitors of Cell Wall Synthesis

A

beta lactams penicillins

cephalosporins

glycopeptides: vancomycin

TB medications

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3
Q

Inhibitors of Translation/Transcription

A

tetracyclines

macrolides

clindamycin

oxazolidinones: linezolid

aminoglycosides and spectinomycin

TB medications

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4
Q

Inhibition of DNA syntheses and integrity/inhibitors of folate synthesis and function

A

sulfonamides, trimethoprim

quinolones

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5
Q

Bactericidal

A

mechanism is generally inhibit cell wall synthesis

time dependent killing

concentration dependent killing

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6
Q

Time Dependent Killing

A

serum level above MIC

beta lactams, vancomycin

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7
Q

Concentration Dependent Killing

A

higher drug concentration determines rate and extent of killing

aminoglycosides, quinolones

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8
Q

Bacteriostatic

A

mechanism is generally inhibition of protein synthesis

tetracyclines, macrolides, sulfonamides

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9
Q

Postantibiotic Effect

A

persistent suppression of bacterial growth after limited exposure to an antimicrobial agent

antibiotic level falls below MIC

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10
Q

Postantibiotic Effect: Proposed Mechanisms

A

slow recovery after reversible non lethal damage to cell structures

persistence of the drug at the binding site

need to synthesize new enzymes before microorganism growth can resume

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11
Q

Penicillin: narrow spectrum

A

Penicillinase susceptible:

  • PCN G
  • PCN VK

Penicillinase resistant:

  • nafcillin
  • oxacillin
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12
Q

Penicillin: wider spectrum

A

+/- penicillinase inhibitor

  • ampicillin
  • amoxicillin
  • piperacillin
  • ticarcillin
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13
Q

What additional microorganisms are covered by amoxicillin but NOT penicillin?

A

H influenza
M catarrhalis
S aureus
Strept

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14
Q

Penicillin: PK

A

rapid renal elimination

some biliary clearance (ampicillin, nafcillin)
-concern for newborns

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15
Q

Penicillin: ADE

A

hypersensitivity rxn

maculopapular rash (ampicllin)

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16
Q

Penicillin: activity spectrum (narrow and wider)

A

Narrow:

  • streptococcal infections
  • staphlococcal infections
  • meningococcal infections
  • syphilis

Wider:
-gram negative bacteria

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17
Q

Cephalosporins: first generation

A

cephalexin

activity:

  • skin
  • soft tissue
  • UTI
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18
Q

Cephalosporins: second generation

A

cefotetan
cefoxitin
cefuroxime

activity:

  • S pneumoniae
  • H influenza
  • B fragilis (cefotetan)
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19
Q

Cephalosporins: third generation

A

ceftriaxone
cefixime
cefotaxime
ceftazidime

activity:
- pneumonia
- meningitis
- gonorrhea
- broad activity(beta lactamase stable)

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20
Q

Cephalosporins: fourth generation

A

cefipime

activity:
-pseudomonas

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21
Q

Cephalosporins: fifth generation

A

ceftaroline

activity:

  • skin
  • soft tissue
  • CA pneumonia
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22
Q

Cephalosporins: PK

A

older: oral
newer: IV

renal elimination

THIRD GENERATION ENTER CNS

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23
Q

Cephalosporins: ADEs

A

hypersensitivity reactions

assume complete cross reactivity bt cephalosporins

1st generation: partial cross reactivity with PCNs

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24
Q

What cephalosporin is not given to newborns?

A

cetriaxone

-displaces bilirubin

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25
Carbapenem
other beta lactam imipenem-cilastatin (primaxin) doripenem meropenem ertapenem broad spectrum activity - PRSP (not MRSA) - gram negative rods - pseudomonas ``` ADEs: CNS effects (confusion, seizures) ```
26
Monobactam
other beta lactam aztreonam no cross reactivity with beta lactams ``` activity: gram negative bacteria -klebsiella -pseudomonas -serratia ``` ADEs: CNS (HA, vertigo)
27
Glycopeptides
vancomycin (MRSA, PRSP) dalbavancin (skin) oritavancin (skin) telavancin (skin, HABP/VABP) activity: gram positive activity
28
Glycopeptides: PK
parenteral for systemic infections oral vancomycin for C difficile colitis renal elimination
29
Glycopeptides: toxicities
red neck/red man syndrome - erythematous rash on face, upper body - cause: infusion rate nephrotoxicity (rare)
30
Daptomycin
lipopeptide PK: renal elimination toxicity: myopathy (weekly CPK/CK) activity: gram positive -endocarditis, sepsis -MSSA, MRSA off label: - osteomyelitis - prosthetic joint infections
31
Tetracycline (30S): agents
tetracycline doxycycline minocycline tigecycline
32
Tetracycline: activity spectrum
``` anthrax chlamydial mycoplasma rickettsiae (RMSF, typhus) spirochetes (lyme disease, relapse fever, syphilis) H pylori ```
33
Tetracycline: uses
acne CAP, bronchitis lyme disease periodontitis off label: - cellulitis (CA MRSA) - acute bacterial rhinosinusitis
34
Tetracycline: ADEs
GI upset interaction with di and trivalent ions deposition in developing bones and teeth*** photosensitivity
35
Macrolide (50S): agents
erythromycin azithromycin (Z pak) clarithromycin
36
Macrolide: ADEs
GI upset hepatic dysfunction QT elongation CYP450 (NOT azithromycin)
37
Macrolide: activity spectrum
CAP pertussis corynebacteria (diphtheria) chlamydial
38
Lincosamdie (50S)
clindamycin activity: - skin infections - soft tissue infections - anaerobic infections ADE: C difficile colitis
39
Chloramphenicol (50S): ADEs
-dose related (aplastic) anemia -gray baby syndrome symptoms: - circulatory collapse - cyanosis - acidosis - abdominal distention - myocardial depression - coma - death risks: - serum levels >50mcg/ml - patients with impaired renal/hepatic function
40
Chloramphenicol: activity spectrum
serious infections (resistant to less toxic abx) - bacteroides - H influenza - N meningitides - salmonella - rickettsia active against many vancomycin resistant enterococci
41
Oxazolidinone
binds to 23S RNA of 50S subunit agent: linezolid activity: - MRSA - PRSP - VRE strains ADEs: - dose related anemia - neuropathy - optic neuritis - serotonin syndrome with SSRIs
42
Aminoglycoside (30S): agents
``` gentamicin tobramycin amikacin streptomycin neomycin ```
43
Aminoglycoside: activity spectrum
aerobic gram negative bacteria H influenza M catarrhalis shigella often used in combination with beta lactams
44
Aminoglycoside: ADEs
nephrotoxicity ototoxicity neuromuscular blockade
45
Antifolates: mechanism sulfonamide, trimethoprim
blockade of folic acid synthesis sulfamethoxazole: - interferes with bacterial folic acid synthesis and growth - inhibition of dihydrofolic acid formation from para-aminonbenzoic acid trimethoprim: - inhibits dihydrofolic acid reduction to tetrahydrofolate - sequential inhibition of enzymes of the folic acid pathway
46
Antifolates: mechanism fluoroquinolones
interfere with bacterial DNA synthesis by inhibiting DNA gyrase inhibits relaxation of supercoiled DNA
47
Sulfonamides with Trimethoprim (Trimethoprim-sulfamethoxazole): activity spectrum
``` UTI traveler's diarrhea respiratory infections ear infections sinus infections P jiroveci pneumonia (HIV) toxoplasmosis (HIV) nocardiosis MSSA/MRSA skin soft tissue infections ```
48
Sulfonamides with Trimethoprim: ADEs
rash fever bone marrow suppression hyperkalemia AIDs patients: - neutropenia - stevens johnson syndrome - toxic epidermal necrolysis
49
What stage of pregnancy should TMP/SMX be avoided?
first trimester after 32 weeks
50
Quinolones: agents
ciprofloxacin levofloxacin gatifloxacin gemfloxacin moxifloxacin ofloxacin
51
Quinolones: activity spectrum
urogenital infections GI tract infections bacterial conjunctivitis
52
Ciprofloxacin, ofloxacin: activity spectrum
UTIs
53
Levofloxacin, gemfloxain, moxifloxacin: activity spectrum
respiratory flouroquinolones gram positive cocci atypicals (chlamydia, mycoplasma)
54
Quinolones: ADEs
``` CNS effects (dizziness, HA) tendinitis peripheral neuropathy neuromuscular blocking activity QTc prolongation (levofloxacin, gemifloxacin, moxifloxacin) ```
55
Quinolones: interaction
oral absorption impaired by cations (Ca, Mg, Al) caution with use of class IA and III antiarrhythmic
56
In what neuromuscular disease should quinolones be avoided?
MYASTHENIA GRAVIS because they disrupt neuromuscular transmission also be wary of macrolides
57
Synergism
inhibitory/killing effects of 2+ antimicrobials used together are significantly greater than expected (than when used individually) fourfold+ reduction in MIC or MBC of each drug
58
Empiric Treatment
antimicrobial agent used before pathogen is identified for particular illness or susceptibility is known
59
Guided Treatment
effective antimicrobial agent identified by susceptibility testing of infecting microorganism
60
Before you prescribe...
``` allergy/hx of ADEs age pregnancy metabolic/genetic variation renal/hepatic function concomitant drug therapy concomitant disease states ```
61
Antibiogram
report of susceptibility/resistance of pathogens to antibiotics information about local resistance patterns used to determine empiric treatment options

PHA 550 (26 decks)

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