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Pharmacology > Antibacterials 3 > Flashcards

Antibacterials 3 Flashcards

1
Q

Describe Cephalosporins

A 
• beta-lactam antibiotics
• Bactericidal
• Same MOA as penicillin's
• Affected by similar resistance mechanisms but less
susceptible to beta-lactamases
• Classified into generations
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2
Q

What are cephalosporins inactive against?

A

All 1st-4th generation cephalosporins are considered
inactive against MRSA,
• All cephalosporins are considered inactive against
Actinotobacteria, Listeria, Legionella, Chlamydia,
Mycoplasma, and Enterococci species (mnemonic :
LAME)

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3
Q

List 1st generation cephalosporins

A

Cefazolin, Cephalexin

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4
Q

Define 1st generation cephalosporins

A

Penicillin G substitutes
• Resistant to staphylococcal penicillinase
• Activity against Gram-positive cocci, P.mirabilis, E.coli, &
K.pneumoniae

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5
Q

What are 1st generation clinical applications?

A

Rarely DOC for any infections

• Cefazolin = DOC for surgical prophylaxis

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6
Q

List 2nd generations cephalosporins?

A

Cefaclor, Cefoxitin, Cefotetan, Cefamandole

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7
Q

Define 2nd generations cephalosporins

A

Extended Gram-negative coverage
• Greater activity against H.influenzae, Enterobacter
aerogenes and some Neisseria species
• Weaker activity against Gram-positive organisms

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8
Q

2nd generation Cephalosporins clinical applications?

A

Primarily used to treat sinusitis, otitis & lower
respiratory tract infections
• Cefotetan & cefoxitin = prophylaxis & therapy of
abdominal and pelvic cavity infections (increased risk of
Gram negative bacteria being present)

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9
Q

List 3rd generation cephalosporins

A

Ceftriaxone, Cefoperazone, Cefotaxime, Ceftazidime,

Cefixime

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10
Q

Define 3rd generation cephalosporins

A

Enhanced activity against Gram-negative cocci
• Highly active against enterobacteriacae, Neisseria, &
H.influenzae
• Cefotaxime, ceftazidime and ceftriaxone = usually active
against pneumococci

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11
Q

Clinical Applications of Ceftriaxone?

A

DOC for gonorrhea
• DOC for empiric treatment of meningitis
• Prophylaxis of meningitis in exposed individuals
• Treatment of disseminated Lyme disease (CNS or
joint infection)

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12
Q

Which two 3rd generation cephalosporins have activity against p. aeruginosa?

A

Cefaperazone, ceftazidime

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13
Q

Identify 4th generation cephalosporin, ROA, and define 4th generation Cephalosporin activity

A

Cefipime, Parenteral admin. Only
• Wide antibacterial spectrum eg, enterobacter,
Haemophilis, Neisseria, E.coli, pneumococci, P.mirabilis
& P.aeruginosa

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14
Q

Clinical applications of Cefipime

A

• Treatment of mixed infections with susceptible
organisms
eg, complicated UTI’s, complicated intra-abdominal
infections, febrile neutropenia

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15
Q

Define and identify 5th generation cephalosporins

A

Ceftaroline
Parenteral admin. only
• Activity against MRSA !
• Similar spectrum of activity to 3rd generatio

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16
Q

Clinical application of Ceftaroline?

A

Skin and soft tissue infection due to MRSA,

particularly if Gram-negative pathogens are coinfecting

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17
Q

Cephalosporins PK?

A

Most administered parenterally (exceptions =
cephalexin, cefaclor, cefixime)
• Only 3rd generation reach adequate levels in CSF
• Mainly eliminated via kidneys (exceptions = ceftriaxone &
cefoperazone excreted in bile)

18
Q

Cephalosporins Adverse events?

A

Allergic reactions (cross-sensitivity with penicillins can
occur)
However, minor penicillin allergic patients often
treated successfully with a cephalosporin
• Pain at infection site (IM), thrombophlebitis (IV)
• Superinfections (eg, C.difficile)
Kernicterus (pregnancy)

19
Q

Cefamandole, cefoperazone & cefotetan contain

methyl-thiotetrazole group, all can cause:

A

• hypoprothrombinemia (Vit. K1 admin can prevent)
&
• disulfiram-like reactions (avoid alcohol)

20
Q

List of Carbapenems

Define Carbapenems

A

Doripenem, Ertapenem, Imipenem & Meropenem
• Synthetic beta-lactam antibiotics
• Resist hydrolysis by most beta-lactamases

21
Q

Describe Carbapenems antibacterial spectrum

A

Very broad spectrum of activity
Ertapenem = less broad, not active against P.aeruginosa
• Active against -lactamase-producing Gram-positive &
negative organisms; aerobes & anaerobes; P.aeruginosa
• Not active against carbapenemase producing
organisms eg, carbapenem-resistant enterobacteriaceae,
carbapenem-resistant klebsiella
• Not active against MRSA

22
Q

Carbapenems Clinical Applications?

A

Use is typically restricted to avoid resistance
• Use limited to life-threatening infections, especially if
broad-spectrum coverage is required
Commonly used for treatment of:
• extended-spectrum beta-lactamase producing Gramnegatives

23
Q

Describe carbapenems PK?

A

IV
• Imipenem forms potentially nephrotoxic metabolite.
Combining with enzyme (dehydropeptidase I) inhibitor
Cilastatin prevents metabolism thus prevents toxicity
& increases availability.
• Doripenem, ertapenem and meropenem are not
metabolized by same enzyme (no need for Cilastatin)

24
Q

Describe Carbapenems adverse effects

A 
GI distress (nausea, vomiting, diarrhea)
• High levels of imipenem can cause CNS toxicity e.g.
seizures
• Allergic reactions
(partial cross-sensitivity with
penicillin’s)
25
Q

What is a monobactam?

A

Aztreonam, ketone group on amide link

26
Q

Monobactum antibacterial spectrum?

A

Aerobic Gram-negative rods ONLY (including
pseudomonas)
• No activity against Gram-positive bacteria or
anaerobes
• Resistant to action of -lactamases

27
Q

Monobactum Clinical applications?

A

UTI’s, lower respiratory tract infections, septicemia,
skin/structure infections, intraabdominal infections,
gynecological infections caused by susceptible Gramnegative
bacteria
• Useful for treatment of Gram-negative infections in
patients allergic to penicillin

28
Q

Describe Monobactum Pharmacokinetics?

A

Mainly IV or IM
• Can be given by inhalation in CF patients
• Penetrates CSF when inflamed
• Excreted primarily via urine

29
Q

Monobactum Adverse Events?

A

Relatively nontoxic
• Little cross-hypersensitivity with other beta-lactam
antibiotics
• Occasional skin rashes and GI upset

30
Q

Define Vancomycin

A

Bacterial glycoprotein
• Active against Gram-positive bacteria only
• Virtually all Gram-negative organisms are intrinsically
resistant
• Effective against multi-drug resistant organisms (eg,
MRSA, enterococci, PRSP)

31
Q

Vancomycin MOA?

A

Binds to the D-Ala-D-Ala terminus of nascent
peptidoglycan pentapeptide
• Inhibits bacterial cell wall synthesis & peptidoglycan
formation
• Not susceptible to beta-lactamases

32
Q

How does bacteria become resistant to vancomycin?

A

• Modification of the D-Ala-D-Ala binding site (D-Ala
replaced by D-lactate)
• Plasmid-mediated changes in drug permeability

33
Q

Vancomycin Clinical Applications?

A

Treatment of serious infections caused by beta-lactam
resistant Gram +ve organisms eg, MRSA
• Treatment of Gram +ve infections in patients severely
allergic to beta-lactams
• In combination with an aminoglycoside for empiric
treatment of infective endocarditis
• In combination with an aminoglycoside for treatment of
Penicillin Resistant Strep Pneumoniae (PRSP)
Given orally for the treatment of staphylococcal
enterocolitis or antibiotic-associated pseudomembranous
colitis (C.difficile)

34
Q

Vancomycin PK?

A

Poor oral absorption
• Requires slow IV infusion (60-90 min)
• Penetrates CSF when inflamed
• 90-100% excreted via kidneys

35
Q

Vancomycin AE?

A

• Mostly minor eg, fever, chills, phlebitis at infusion site
• ‘Red man’ or ‘red neck’ syndrome (infusion-related
flushing over face and upper torso)
• Ototoxicity (drug accumulation)
• Nephrotoxicity (drug accumulation)

36
Q

Describe Daptomycin?

A

Bactericidal
• Effective against resistant Gram-positive organisms
(eg, MRSA, enterococci, VRE & VRSA)
• Inactive against Gram-negative bacteria
• Not effective in treatment of pneumonia

37
Q

Daptomycin MOA?

A

• Novel mechanism of action -> useful against multi-drug
resistant bacteria
• Binds to cell membrane via calcium-dependent insertion
of lipid tail
• Results in depolarization of cell membrane with K+ efflux
-> cell death

38
Q

Daptomycin Clinical application?

A

Recommended for treatment of severe infections
caused by MRSA or VRE
• Treatment of complicated skin/structure infections
caused by susceptible S.aureus

39
Q

Daptomycin PK?

A

IV only

can accumulate in renal insufficiency

40
Q

Daptomycin AE?

A

Constipation, nausea, headache, insomnia
• Elevated creatine phosphokinases (recommended to
discontinue coadmin. of statins)

41
Q

Define Bacitracin?

A
  • Unique mechanisms -> no cross resistance
  • Interferes in late stage cell wall synthesis
  • Effective against Gram-positive organisms
  • Marked nephrotoxicity -> mainly topical use
42
Q

Define Fosfomycin

A

Inhibits cytoplasmic enzyme enolpyruvate transferase in
early stage of cell wall synthesis
• Active against Gram-positive and negative organisms
• Oral
• Used for treatment of uncomplicated lower UTI’s

Pharmacology (49 decks)

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