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What important structure of the Penicillins, Cephalosporins, and Carbapenems affords it their antibacterial effectiveness?
Have a unique 4-membered lactam ring
Regarding the chemistry of the beta lactam antiobiotics, what structural component of the nucleus is essential for biologic activity?
- thiazolidine ring attached
- to the beta-lactam ring
How can bacteria reduce the effectiveness of the beta lactams?
Hydrolysis of beta-lactam ring by bacterial beta-lactamases causes loss of antibacterial activity
What are the 3 classifications for the beta lactams and give an example of each?
- Penicillins (Penicillin G)
- Anti-staphylococcus Penicillins (Nafcillin)
- Extended sprectrum Penicillins (Ampicillin)
Describe the MOA for the beta lactams.
- Beta-lactam antibiotics covalently bind to active site
- of penicillin binding proteins (PBPs) or
- transpeptidase enzyme. This inhibits transpeptidation reaction halting
- peptidoglycan synthesis in the cell wall, thus
- inhibiting bacterial growth & causing cell death.
Beta Lactams can only kill organisms that are ______________ and synthesizing a ________________?
Regarding resistance of to the beta lactams, list 4 general causal mechanism.
- 1. Inactivation of antibiotic by beta-lactamase
- 2. Modification of target PBPs
- 3. Impaired penetration of drug to target PBPs
- 4. Efflux
What is the most common of resistance to beta lactams?
- Beta-lactamase production is most common mechanism of
What is the basis for resistance seen with methicillin resistance in staphylococci & penicillin resistance in pneumococci?
Impaired penetration of antibiotic to target PBPs
- occurs only in this type of organism due to their impermeable outer cell wall?
- Gram negative species
Regarding porins, what 2 alterations can impair entry of drug into the cell?
Absence and down-regulation
Gram (-) organisms can also produce ____________
- that transport beta-lactam antibiotics back out of
- the cell across the outer membrane?
- Efflux pumps
Absorption of most oral PCNs is impaired by food &
- should be administered when relative to a meal?
- 1-2 hours before or after
CN concentrations in most tissues are ___________ to those
With active inflammation of the meninges, what will happen in terms of CNS penetration of the beta lactams?
It will be improved
Beta lactams are excreted in breast milk and sputum? True or false
Describe the excretion pattern seen by many beta lactams?
- glomerular filtration
- 90% tubular secretion
Name 3 beta lactams that are cleared the kidney and biliary system.
- dicloxacillin, & cloxacillin
Which of the beta lactams is primarily excreted by biliary excretion?
Name 2 anti-pseudomonal PCNs.
Regarding the PCNs and hypersensitivity, all PCNs are ______________ & _________________?
- crossing sensitizing
- cross reacting
Name 3 types of adverse allergic reactions associated with PCNs?
- Anaphylactic shock (rare)
- serum sickness type reaction (urticaria, fever, respiratory compromise 7-12 days)
- skin rashes
What allergic kidney condtion can be associated with PCN therapy?
Patients with an allergy to PCN, can be desensitized. How is this done generally?
- Desensitization can be done with protocol of gradually
- increasing doses of PCN
What gastrointestinal symptoms are associated with large doses of PCN?
Nausea, vomiting, diarrhea
These 2 PCN can cause skin rashes that are not
- allergic in nature and are seen when viral illness is present?
- Ampicillin & amoxacillin
- Cephalosporins are not active against these 2 organisms?
- Enterococci & Listeria
What are the classifications of the cephalosporins?
First, second, third, fourth & fifth generations
First cephalosporins are very active against this type of organism?
Name 3 types of infections that FIRST generation cephalosporins are effective against.
- skin infections
- surgical prophylaxis
Excretion is mainly by _______________ & ____________________ into urine?
- glomerular filtration
FIRST generation cephalosporins should not be used to treat meningitis, why?
Does not penetrate CNS well
What organisms do the SECOND generation cephalosporins work on?
All FIRST generation organisms plus coverage against gram negatives
Name 3 infections that SECOND generation cephalosporins are effective against.
- lower respiratory tract infections
What pharmacokinetic characteristic might make THIRD generation cephalosporins superior to SECOND generation?
- Expanded gram (-) coverage & some are able to
- cross blood-brain barrier
Of the THIRD generation cephalosporins, which 2 do not need to renally dosed? Why?
Cefoperazone & Ceftriaxone, due to being biliary excreted
Fourth generation cephalosporins have ________________ stability against beta lactamases?
Which generation is active against methicillin resistant strains of staphylococci?
Frequency of cross-allergenicity between PCNs &
- Cephalosporins is seen most commonly with which generation?
- More common with the early generations vs. later
Patients with history of anaphylaxis to PCNs should
- not receive Cephalosporins? TRUE or FALSE
Aztreonam's activity is limited to this type of organism?
aerobic gram (-) rods including pseudomonas
Name 2 beta lactam medication that are the treatment of choice for infections caused by ESBL
- producing gram (-) bacteria?
Name the antibiotic that is known as a glycopeptide.
How does Vancomycin essentially kill an organism?
Inhibiting cell wall synthesis
Name 3 common uses for vancomycin.
What are the goal trough concentrations of Vancomycin for mild-moderate infections & severe infections?
- Mild-moderate: 10-15 mcg/ml
- Severe: 15-20 mcg/ml
Oral administration of vancomycin is only used for this condition?
Clostridium difficile colitis
Name 4 adverse reactions associated with vancomycin.
Name 2 general interventions to reduce ototoxicity & nephrotoxicity associated with vancomycin.
- Avoid concomitant use other nephrotoxic medications
- keep peak levels <60 mcg/ml
What is the name of the adverse syndrome associated with vancomycin infusion and is due to histamine release?
“red man” syndrome
Name 2 ways to treat “red man” syndrome?
- Reduce infusion time or dose
- anti-histamine pretreatment
What are 2 adverse reactions associated with the membrane-active antibiotic classification?
- Myopathy & allergic pneumonitis
- Why should the membrane-active antiobiotics not be used to treat pneumonia?
- They are inactivated by pulmonary surfactant
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