C. 8. Penicillins Flashcards
what are Beta-lactam antibiotics?
Ab that inhibits cell wall synthesis
they all have β-lactam ring
what does a peptidoglycan layer consist of?
a chain of cross-linked disaccharide residues of N-acetylglucosamine and N-acetylmuramic acid
what are the targets of beta-lactam Ab?
Penicillin-binding-proteins (PBP’s)
where are PBP’s located?
on the cell wall of bacteria (peptidoglycan layer)
what is the effect of β-lactam Ab?
when exposed to bacteria, they bind to specific PBP’s on the bacterial cell wall and inhibit the assembly of the peptidoglycan chains–> this activates autolysin enzymes that degrade the cell wall–> bactericidal effect
what is the major mechanism of bacterial resistance?
β-lactamases (penicillinases)
what do β-lactamases do?
enzymatic hydrolysis of the β-lactam ring resulting in loss of antibacterial activity
what is the clinical presentation of interstitial nephritis?
fever oliguria BUN/Cr ratio ↑ Eosinophils in urine WBC casts -->'sterile pyuria'
commonly used combination preparations
Amoxicillin+ Clavulanic avid (β- lactamase inhibitor)
Ampicillin/Sulbactam
Piperacillin/Tazobactam
what ↑ penicillin in serum concentration?
probenecid
can penicillin cross the BBB?
only when the meninges are inflamed
penicillin synergistic effect with…
aminoglycosides
what happens when we combine penicillin with β- lactamase inhibitors (clavulanic acid, sulbactam, tazobactam)?
enhanced activity
what is the T1/2 of penicillin?
30-60 min
what are the mechanisms of intrinsic resistance of penicillin?
- no cell wall (mycoplasma, ureaplasma)
- intracellular parasites (chlamydia, rickettsia)
- slowly-growing bacteria (mycoplasma)
what are the mechanisms of acquired resistance of penicillin?
- penicillinases–> break lactam ring structure (staphylococci)
- structure change in PBP’s (MRSA, PRSP)
- change in porin structure (pseudomonas)
list the narrow spectrum, β- lactamase sensitive penicillins
Penicillin G (iv) and Penicillin V (ORAL) -natural Benzathine Peniciliin G (IM)
what is the indication for Benzathine penicillin G and how is it given?
syphilis (T.pallidum)
IM depot injection (slow-release formulation)
indications for natural penicillin
- streptococcal infections
- gram + rods (actinomyces israelii)
- clostridium perfringes (gas gangrene)
- enterococci
- prophylaxis against strep. agalactiae
- Neisseria meningitidis &gonorrhea
side effects of natural penicillin
- hypersensitivity/ allergic reaction
- drug-induced hemolytic anemia (IgG-mediated)
- interstitial nephritis
- Jarisch- Herxheimer reaction- syphilis treatment
symptoms for hypersensitivity reaction from penicillin
fever, urticaria, pruritus, joint swelling, angioedema, anaphylaxis (IgE-mediated)
symptoms of Jarisch- Herxheimer reaction
fever, chills, flushing, hyperventilation
list the very- narrow spectrum, β- lactamase resistant penicillins
Oxacillin
Methicillin
Nafcillin (IV)
Dicloxacillin
list the broad spectrum, β- lactamase sensitive penicillins
Ampicillin
Amoxicillin
name 2 extended-spectrum, β- lactamase sensitive penicillins and how is it given
Piperacillin (IV)
Ticarcillin (IV)
when do you give Piperacillin and Ticarcillin?
pseudomonas (‘anti-pseudomonal peniciilins’)
sepsis
when do we give Oxacillin?
staphylococcal infections–> skin &soft tissue infections, endocarditis, osteomyelitis
DO NOT COVER MRSA
side effects of very- narrow spectrum, β- lactamase resistant penicillins
interstitial nephritis–> methicillin
Neutropenia –> Nafcillin
side effects of broad/extensive-spectrum, β- lactamase sensitive penicillins
- Maculopapular skin rash (pseudoallergy) –> ampicillin given in EBV infection
- GI disturbances (most severe dysbacteriosis with ampicillin)
- Stevens- Johnsons syndrome
- Hepatotoxicity (amoxicillin+clavulanate)
indications for broad-spectrum, β- lactamase sensitive penicillins
similar to penicillin G + ↑ activity against gram -rods
AM-CILLIN “HHELPSSS” kill enterococci
H. influenza (pneumonia,otitis media & sinusitis )
H.pylori (triple therapy)
E.coli
Listeria monocytogenes
Proteus mirabilis (Uncomplicated UTI)
Salmonella
Shigella
S. Pneumoniae (otitis media & sinusitis )
also: anaerobic infections, Borrelia Burgdorferi (lyme)
prophylaxis: high-risk patients prior to dental procedures, asplenic patients with fever
