-
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
- resistance
-
What is the basis for resistance seen with methicillin resistance in staphylococci & penicillin resistance in pneumococci?
Altered PBPs
-
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
TRUE
-
Describe the excretion pattern seen by many beta lactams?
- 10%
- glomerular filtration
- 90% tubular secretion
-
Name 3 beta lactams that are cleared the kidney and biliary system.
- Oxacillin,
- dicloxacillin, & cloxacillin
-
Which of the beta lactams is primarily excreted by biliary excretion?
Nafcillin
-
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?
Interstitial nephritis
-
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
- monocytogenes
-
What are the classifications of the cephalosporins?
First, second, third, fourth & fifth generations
-
First cephalosporins are very active against this type of organism?
Gram positive
-
Name 3 types of infections that FIRST generation cephalosporins are effective against.
- UTI
- skin infections
- surgical prophylaxis
-
Excretion is mainly by _______________ & ____________________ into urine?
- glomerular filtration
- tubular
- secretion
-
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.
- Sinusitis
- otitis
- 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?
Improved
-
Which generation is active against methicillin resistant strains of staphylococci?
Fifth
-
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
- TRUE
-
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?
- Doripenem
- Ertapenem
- Imipenem
- Meropenem
-
Name the antibiotic that is known as a glycopeptide.
Vancomycin
-
How does Vancomycin essentially kill an organism?
Inhibiting cell wall synthesis
-
Name 3 common uses for vancomycin.
- Sepsis
- endocarditis
- meningitis
-
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.
- Phlebitis
- fever
- ototoxicity
- nephrotoxicity
-
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
|
|
