Antibacterials 2 Flashcards
List cell wall synthesis Inhibitors
-lactam antibiotics • penicillins • cephalosporins • carbapenems • monobactams • Vancomycin • Daptomycin • Bacitracin • Fosfomycin
List beta lactamase inhibitors
Clavulanic Acid, Sulbactam, Tazobactam
What do Beta Lactmase inhibitors do?
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
Beta-lactams MOA?
• 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
Describe Penicillins Antibacterial Spectrum?
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
Synergistic combination with Penicillin?
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
4 general mechanisms of Penicillin resistnace
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
Describe Penicillin G(natural penicillin, benzylpenicillin) activity
Benzylpenicillin • Active against: • most Gram-positive cocci • Gram-positive rods • Gram-negative cocci • most anaerobes • Susceptible to inactivation by beta-lactamases
3 Penicillin G clinical applications?
Mostly used for Gram + organisms, commonly used for: • Syphilis (benzathine penicillin G) • Strep infections • Susceptible pneumococci
List the repository Penicllins? Why were they developed?
Penicillin G Procaine, Penicillin G Benzathine
Developed to prolong duration of penicillin G
Penicillin G procaine route of administration, half-life, and frequency of use?
IM not IV (risk of procaine toxicity)
• t1/2 = 12-24h
• Seldom used (increased resistance)
Penicillin G Benzathine route of administration and half life?
IM
half-life= 3-4 weeks
Penicillin G Benzathine Clinical Applications?
Syphilis
Rheumatic fever prophylaxis
Describe Penicillin V
Natural penicillin
Similar antibacterial spectrum to penicillin G (less active
against Gram –ve bacteria)
• More acid stable than G (can give orally
)
Penicillin V clinical applications
Employed mostly orally for mild-moderate infections eg,
pharyngitis, tonsilitis, skin infections (caused by Strep
)
list antistaphylococcal penicillins? 2 characteristic features?
Methicillin, Nafcillin, Oxacillin, Dicloxacillin
beta-lactamase resistant
Inactive against MRSA
Methicillin, Nafcillin, Oxacillin, Dicloxacillin Clinical applications?
Restricted to treatment of
beta-lactamase-producing
staphylococci
Describe Extended Spectrum Penicllins
Ampicillin, Amoxicillin Similar to penicillin G (plus Gram-negative activity) • Susceptible to beta-lactamases • Activity enhanced with -lactamase inhibitor
What differentiates Amoxicillin from other penicillins? Who is amoxicillin commonly prescribed to?
Amoxicillin has higher oral bioavailability than other
penicillins (including ampicillin)
• Amoxicillin is a common antibiotic prescribed for
children and in pregnancy
Describe 4 clinical applications of Amoxicillin
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
Describe Ampicillin Clinical applications?
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
List Antipseudomonas Penicillins
Carbenicillin, Ticarcillin, Piperacillin
Describe Antipseudomonas Penicillins
Effective against many Gram-negative and Grampositive
bacilli
• Often combined with beta-lactamase inhibitor
• Active against P.aeruginosa
Carbenicillin, Ticarcillin, Piperacillin
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)
Describe half life and oral absorption of Penicillins
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.)
Describe the distribution of Penicillins
• 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)
Describe excretion of Penicillins
Excretion
• Most excreted primarily via kidney (beware in
kidney failure)
• Nafcillin = exception as primarily excreted in
bile
• Oxacillin & dicloxacillin = renal & biliary excretion
Describe hypersensitivity to penicillins
Hypersensitivity
• Penicilloic acid = major antigenic determinant
• ~ 5 % patients claim to have some reaction
(maculopapular rash anaphylaxis)
• Cross-allergic reactions between -lactam
antibiotics can occur
Describe Allergic Reactions to penicillins
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)
