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important?
(E) Cigarette smoking, diet, drug use, and obesity are not well-established factors that
influence the risk for breast cancer. All others listed are known risk factors.
Exam Questions:
o DOC for syphillis (benzathine penicillin),
o DOC in strep infections, especially to prevent rheumatic fever
o DOC for susceptible pneumococci
Antibiotics:
1. All cell wall inhibitors are β –lactms except Vancomycin.
Β-lactams: Monobactam, cephalasporin, carbapenem, penicillin
Mechanism of Action
i. All beta-lactams bind penicillin-binding proteins (PBP’s)
ii. All beta-lactams block transpeptidase cross-linking of cell wall
iii. Activate autolytic enzymes, causing osmotic damage (bactericidal)
Mechanism of resistance
i. β lactamase production (S. aureus)
ii. Change their structure of PBPs (e.g. MRSA, thus must use vancomycin)
iii. Efflux pump or change in porin structure (gram-negatives ie pseudomonas)
First Generation Penicillin G and V
i. Narrow spectrum (mainly gram positives)
ii. Sensitive to β –lactamases – thus never use for Staph
Second Generation Methicillin (made to overcome β –lactamse resistance..but
became so specific, its only used against staph..and thus created the famous MRSA)
Third Generation Aminopenicillins e.g. Ampicillin, Amoxicillin
i. Clinical use: broad spectrum (gram positives and negatives, but NOT β –
lactamase resistant)
ii. H.flu, listeria, Lyme Disease in children and pregnant women, Enterococci
Cluvanic acid is now used to protect the aminopenicillins from β –lactamases.
Fourth Generation anti-pseudomonal penicillins.
i. Synergistic effect when combined with aminoglycosides.
ii. Parenteral penicillins usually combined with beta-lactamase inhibitors
Rule: all penicillins are water soluble, except nafcillin. Thus excreted by kidneys –
potentially renal toxic. Can’t cross BBB, no good for meningitis.
Rule: penicillins cause allergies
First generation: Cephalasporins cephalexin, cephradine, cefazolin
i. Clinical use: gram positives and few gram negatives PEcK (proteus, e.coli,
kelbsiella)
ii. Cannot enter CNS
Second Generation Cephalasporins
i. HEN PEcKS
ii. Gram negatives: H. flu, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella,
Serratia
iii. Cannot enter CNS except cefuroxamine.
Third Generation Cephalasporins
i. Cephtriaxone, cefotaxime, ceftazidime
ii. 1st generation + 2nd generation = 3rd generation (gram positive and
negative) +anaerobes
iii. Ceftriaxone is lipid soluble, thus can enter CNS, metabolized by p450 and
excreted into bowel.
iv. Ceftazidime for pseudomonaz
v. Ceftriaxone for gonorrhea and meningitis
Fourth Generation Cephalasporins – Cefepime, Cefpirome
i. Clincal use: 3rd Generation + more beta-lactamase resistance
Monobactam - Aztreonam
i. Same MOA as penicillins
ii. Synergistic with aminoglycosides
iii. Resistant to β –lactamases
iv. Clinical use: gram neg rods only (pseudomonas)
v. Toxicity: no cross-allerginicity with penicilins
Carbapenems – imipenem, meropenem
i. β –lactamase resistant
ii. Works on anything
iii. BUT can cause CNS toxicity (seizures)
Vancomycin
i. Inhibits cell wall mucopeptide formation by binding D-ala-D-ala portion of
cell wall precursors. Resistance occurs when changed to D-ala D-lac.
ii. Clinical use: gram positive multidrug resistant organisms e.g. MRSA, C.Diff
iii. Toxicity: kidney and ears, red man syndrome with rapid infusion
2. Rule: All protein synthesis inhibitors are bacteriostatic, except for the aminoglycosides