Antibacterials 2

Question 1

List cell wall synthesis Inhibitors

Answer 1

-lactam antibiotics
• penicillins
• cephalosporins
• carbapenems
• monobactams
• Vancomycin
• Daptomycin
• Bacitracin
• Fosfomycin

Question 2

List beta lactamase inhibitors

Answer 2

Clavulanic Acid, Sulbactam, Tazobactam

Question 3

What do Beta Lactmase inhibitors do?

Answer 3

Contain beta-lactam ring but do not have sig. antibacterial
activity
• Bind to and inactivate most beta-lactamases
• Available only in fixed combinations with specific
penicillins

Question 4

Beta-lactams MOA?

Answer 4

• Bactericidal
• Inhibit last step in peptidoglycan synthesis through binding
to PBPs
• Activate autolytic enzymes to initiate cell death
Bacteria eventually lyse due to activity of autolysins
and inhibition of cell-wall assembly

Question 5

Describe Penicillins Antibacterial Spectrum?

Answer 5

Ability to ‘reach’ PBPs determined by:
• size
• charge
• hydrophobicity
Gram-positive bacteria have cell wall easily crossed by
penicillin's
Gram-negative bacteria have porins (channels) to
permit transmembrane entry

Question 6

Synergistic combination with Penicillin?

Answer 6

Pencillin + aminoglycoside
• Penicillins facilitate movement of aminoglycosides through
cell wall
• Should never be placed in same infusion fluid (form
inactive complex)
• Effective empiric treatment for infective endocarditis

Question 7

4 general mechanisms of Penicillin resistnace

Answer 7

Inactivation by
beta-lactamase
• Modification of target PBPs
• Impaired penetration of drug to target PBPs
• Increased efflux
MRSA = altered target PBPs (low affinity for
beta-lactam
antibiotics

Question 8

Describe Penicillin G(natural penicillin, benzylpenicillin) activity

Answer 8

Benzylpenicillin
• Active against:
• most Gram-positive cocci
• Gram-positive rods
• Gram-negative cocci
• most anaerobes
• Susceptible to inactivation by beta-lactamases

Question 9

3 Penicillin G clinical applications?

Answer 9

Mostly used for Gram + organisms, commonly used
for:
• Syphilis (benzathine penicillin G)
• Strep infections
• Susceptible pneumococci

Question 10

List the repository Penicllins? Why were they developed?

Answer 10

Penicillin G Procaine, Penicillin G Benzathine

Developed to prolong duration of penicillin G

Question 11

Penicillin G procaine route of administration, half-life, and frequency of use?

Answer 11

IM not IV (risk of procaine toxicity)
• t1/2 = 12-24h
• Seldom used (increased resistance)

Question 12

Penicillin G Benzathine route of administration and half life?

Answer 12

IM

half-life= 3-4 weeks

Question 13

Penicillin G Benzathine Clinical Applications?

Answer 13

Syphilis

Rheumatic fever prophylaxis

Question 14

Describe Penicillin V

Answer 14

Natural penicillin
Similar antibacterial spectrum to penicillin G (less active
against Gram –ve bacteria)
• More acid stable than G (can give orally
)

Question 15

Penicillin V clinical applications

Answer 15

Employed mostly orally for mild-moderate infections eg,
pharyngitis, tonsilitis, skin infections (caused by Strep
)

Question 16

list antistaphylococcal penicillins? 2 characteristic features?

Answer 16

Methicillin, Nafcillin, Oxacillin, Dicloxacillin
beta-lactamase resistant
Inactive against MRSA

Question 17

Methicillin, Nafcillin, Oxacillin, Dicloxacillin Clinical applications?

Answer 17

Restricted to treatment of
beta-lactamase-producing
staphylococci

Question 18

Describe Extended Spectrum Penicllins

Answer 18

Ampicillin, Amoxicillin
Similar to penicillin G (plus Gram-negative activity)
• Susceptible to
beta-lactamases
• Activity enhanced with
-lactamase inhibitor

Question 19

What differentiates Amoxicillin from other penicillins? Who is amoxicillin commonly prescribed to?

Answer 19

Amoxicillin has higher oral bioavailability than other
penicillins (including ampicillin)
• Amoxicillin is a common antibiotic prescribed for
children and in pregnancy

Question 20

Describe 4 clinical applications of Amoxicillin

Answer 20

Used for treatment of a number of infections: acute otitis
media, streptococcal pharyngitis, pneumonia, skin
infections, UTIs etc.
• Widely used to treat upper respiratory infections
• Can be used for prophylaxis of susceptible infections
• Amoxicillin + clavulanic acid is the preferred prophylactic
treatment for dog, cat, and human bites

Question 21

Describe Ampicillin Clinical applications?

Answer 21

Basically the IM version of amoxicillin
• Used for treatment of a number of infections: acute otitis
media, streptococcal pharyngitis, pneumonia, skin
infections, UTIs etc.
• Ampicillin + sulbactam is the preferred treatment for dog,
cat, and human bites

Question 22

List Antipseudomonas Penicillins

Answer 22

Carbenicillin, Ticarcillin, Piperacillin

Question 23

Describe Antipseudomonas Penicillins

Answer 23

Effective against many Gram-negative and Grampositive
bacilli
• Often combined with beta-lactamase inhibitor
• Active against P.aeruginosa

Question 24

Carbenicillin, Ticarcillin, Piperacillin

Answer 24

Commonly used to treat Pseudomonas aeruginosa
• Main clinical use = as an injectable treatment of Gram
negatives
• Treatment of moderate-severe infections of
susceptible organisms (eg, uncomplicated &
complicated skin, gynecologic and intra-abdominal
infections, febrile neutropenia)

Question 25

Describe half life and oral absorption of Penicillins

Answer 25

Half-life • ~30-60 min (except repository penicillins) Oral absorption • Absorption impaired by food (except amoxicillin  high oral bioavailability) • Nafcillin = erratic (not suitable for oral admin.)

Question 26

Describe the distribution of Penicillins

Answer 26

• All achieve therapeutic levels in pleural, pericardial, peritoneal, synovial fluids & urine • Nafcillin, ampicillin & piperacillin achieve high levels in bile, • Levels in prostate & eye = insufficient • CSF penetration = poor (except in meningitis)

Question 27

Describe excretion of Penicillins

Answer 27

Excretion • Most excreted primarily via kidney (beware in kidney failure) • Nafcillin = exception as primarily excreted in bile • Oxacillin & dicloxacillin = renal & biliary excretion

Question 28

Describe hypersensitivity to penicillins

Answer 28

Hypersensitivity • Penicilloic acid = major antigenic determinant • ~ 5 % patients claim to have some reaction (maculopapular rash  anaphylaxis) • Cross-allergic reactions between -lactam antibiotics can occur

Question 29

Describe Allergic Reactions to penicillins

Answer 29

GI disturbances (eg, diarrhea) • Pseudomembranous colitis (ampicillin) • Maculopapular rash (ampicillin, amoxicillin) • Interstitial nephritis (particularly methicillin) • Neurotoxicity (epileptic patients at risk) • Hematologic toxicities (ticarcillin) • Neutropenia (nafcillin) • Hepatitis (oxacillin) • Positive Coombs Test (penicillin G, V) • Secondary infections (eg, vaginal candidiasis)