Penicillin Discovery and Bacterial Resistance

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Questions and Answers

What is the primary advantage of anti-staphylococcus penicillins?

They can easily break down β-lactamases.

They are not affected by β-lactamases. (correct)

They are effective against all strains of Staphylococcus.

They are broad-spectrum antibiotics.

Which combination is used to enhance the effectiveness of amoxicillin?

Amoxicillin and methicillin

Amoxicillin and oxacillin

Amoxicillin and clavulanic acid (correct)

Amoxicillin and tazobactam

Which of the following anti-staphylococcus penicillins has been withdrawn from use due to MRSA?

Flucloxacillin

Oxacillin

Dicloxacillin

Methicillin (correct)

What defines anti-pseudomonal penicillins?

They are the first choice for Pseudomonas aeruginosa infections. Signup and view all the answers

What is the role of clavulanate when used with amoxicillin?

It competitively inhibits β-lactamase. Signup and view all the answers

What is the primary mechanism by which β-lactamases confer resistance to bacteria?

By breaking down the β-lactam structure Signup and view all the answers

How can plasmid-encoded β-lactam resistance be spread among bacterial strains?

Through conjugation Signup and view all the answers

What role do penicillin binding proteins (PBPs) play in bacterial resistance to β-lactams?

They perform peptidoglycan cross-linking. Signup and view all the answers

Which amino acid is specifically mentioned as being crucial for the binding of β-lactams to PBPs?

Serine Signup and view all the answers

What is a PBP mutation and how does it lead to antibiotic resistance?

An alteration in the amino acid sequence of PBPs Signup and view all the answers

Which class of antibiotics is primarily affected by β-lactamases?

β-lactams Signup and view all the answers

What happens when a bacterial PBP mutates to have a lower affinity for a β-lactam antibiotic?

The bacteria become resistant to the antibiotic. Signup and view all the answers

How many different classes of β-lactamases have been characterized according to the content?

Over 300 Signup and view all the answers

What is a potential side effect of excessive vancomycin infusion?

Erythematous rash Signup and view all the answers

How does resistance to vancomycin occur in bacteria?

By modifying D-Ala-D-Ala to D-Ala-D-Lac Signup and view all the answers

Which bacteria serves as a reservoir for antibiotic resistance traits due to cephalosporin and vancomycin use?

Enterococcus faecalis Signup and view all the answers

What is a major concern regarding vancomycin-resistant Enterococcus faecalis?

It may transfer resistance traits to Staphylococcus aureus Signup and view all the answers

What can help narrow the chances of antibiotic resistance spreading?

Narrowing down therapy Signup and view all the answers

What structural feature is common to all penicillins?

It has a β-lactam ring structure. Signup and view all the answers

How do β-lactam antibiotics inhibit bacterial growth?

By forming covalent bonds with transpeptidase enzyme. Signup and view all the answers

What is a major reason for the rapid development of bacterial resistance to penicillin?

Mutations occur under selection pressure from drug exposure. Signup and view all the answers

Which component of bacterial cells is primarily affected by penicillins?

Cell wall synthesis. Signup and view all the answers

What is a consequence of the β-lactam ring's structural instability?

It leads to frequent hydrolysis in high acidity. Signup and view all the answers

In what year was penicillin first clinically trialed in humans?

1943 Signup and view all the answers

What causes bacterial cells to burst when treated with β-lactams?

Inactivating the transpeptidase enzyme. Signup and view all the answers

Which statement is true regarding bacterial β-lactamase enzymes?

They are a significant cause of antibiotic resistance. Signup and view all the answers

Which of the following is a characteristic of cefepime?

It has a wide antibacterial spectrum. Signup and view all the answers

What should be done for patients with renal dysfunction when administering cephalosporins?

Reduce the dosages to prevent toxicity. Signup and view all the answers

Which organisms are effectively targeted by cefepime?

Aerobic Gram-negative organisms, such as E.coli. Signup and view all the answers

In which situation should cephalosporins be avoided?

If the patient has a penicillin allergy. Signup and view all the answers

What is a common adverse drug effect (ADE) associated with cephalosporins?

Diarrhea Signup and view all the answers

What is the reason for the reduced effectiveness of cephalosporins against certain bacteria?

Their vulnerability to certain β-lactamases. Signup and view all the answers

What distinguishes carbapenems from other β-lactams?

They are synthetic β-lactams. Signup and view all the answers

Which statement about cefazolin is correct?

It penetrates bone effectively. Signup and view all the answers

Study Notes

Penicillin Discovery and Properties

Alexander Fleming discovered penicillin by observing clear zones of inhibition around a fungal colony in a bacterial culture.
Penicillin was purified and trialed clinically in humans in 1943.
Penicillin is a β-lactam antibiotic that inhibits bacterial cell wall synthesis by forming a covalent bond with the bacterial transpeptidase enzyme, inactivating it and preventing cross-linking.
Penicillins are prone to degradation by bacterial β-lactamase enzymes.

Bacterial Resistance to Penicillin

Bacterial resistance to penicillin arose within 15 years of its clinical use.
Resistance develops via spontaneous random mutation, with resistant strains having a selective growth advantage over susceptible ones.
β-lactamase enzymes, encoded by genes within bacterial plasmids, can be spread between strains through conjugation.
β-lactamases hydrolyze the β-lactam ring, rendering the antibiotic ineffective.
Bacteria can also mutate their own penicillin-binding protein (PBP), changing its affinity for the antibiotic.

Modified Penicillins to Overcome Resistance

Modified penicillins, like flucloxacillin, dicloxacillin, and oxacillin, were designed to resist β-lactamase degradation.
Methicillin, another β-lactamase-resistant penicillin, has been withdrawn due to the emergence of MRSA.
MRSA strains are resistant to flucloxacillin, dicloxacillin, and oxacillin.

Broad Spectrum Penicillins and Combinations

Amoxicillin and ampicillin are broad-spectrum penicillins.
Amoxicillin can be combined with a β-lactamase inhibitor, clavulanic acid, to form Augmentin, which increases its effectiveness against β-lactamase producing bacteria.

Anti-pseudomonal Penicillins

Piperacillin and ticarcillin are anti-pseudomonal penicillins with a wide spectrum of activity, especially effective against Pseudomonas aeruginosa infections.
Piperacillin is often combined with tazobactam, and ticarcillin with clavulanic acid, to overcome β-lactamase resistance.

Cephalosporins

Cephalosporins are a class of β-lactam antibiotics with a similar mechanism of action to penicillin.
They are generally well tolerated but can cause allergic reactions.
They are divided into generations, with newer generations having broader spectrum activity.
Resistance to cephalosporins can arise through the production of extended-spectrum β-lactamases (ESBLs).
Cephalosporins can be administered intravenously or intramuscularly due to poor oral absorption.

Carbapenams

Carbapenams are synthetic β-lactam antibiotics with a wide spectrum of activity
They are effective against many β-lactamase-producing bacteria.
They can be used orally to treat severe antibiotic-associated C. difficile colitis infections.

Vancomycin

Vancomycin is a glycopeptide antibiotic that inhibits cell wall synthesis by binding to the terminal D-Ala-D-Ala residues of peptidoglycan precursors.
It is effective against Gram-positive bacteria, especially those resistant to other antibiotics.
Vancomycin resistance can arise by bacterial production of a new pentapeptide that ends in D-Ala-D-Lac, which does not bind vancomycin.
Vancomycin-resistant Enterococci (VRE) are a significant concern.

Enterococcus faecalis and Antibiotic Resistance

Widespread use of antibiotics such as cephalosporins and vancomycin has led to the proliferation of E. faecalis.
E. faecalis has developed resistance to vancomycin and can transfer these resistance genes to other pathogens like S. aureus.
This makes it a significant reservoir of antibiotic-resistance traits.

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Description

Explore the groundbreaking discovery of penicillin by Alexander Fleming and its properties as an antibiotic. Learn about the significant issue of bacterial resistance that emerged shortly after its introduction and the mechanisms by which bacteria develop resistance.