Antibiotics and Beta-Lactamase Quiz

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Questions and Answers

Which statement about metallo-β-lactamase subclasses is accurate?

Subclass B2's catalytic species is inhibited by a second zinc cation. (correct)

Subclass B1 has a weaker affinity for zinc than subclass B2.

Subclass B3 is characterized by a mono-zinc system.

Subclass B1 lacks a cooperative zinc binding.

What is the primary use of clavulanic acid?

As a broad-spectrum antibiotic.

As a substitute for amoxicillin.

As a powerful irreversible inhibitor of β-lactamases. (correct)

As a growth enhancer in bacterial cultures.

Which characteristic is essential to the structure-activity relationship (SAR) of clavulanic acid?

Unstrained carboxylic acid group.

Trans-configuration at the C=C bond.

Strained β-lactam ring. (correct)

Presence of substituent at C-6.

What distinguishes tazobactam from sulbactam?

Tazobactam exhibits decent potency with a broad spectrum. Signup and view all the answers

Which of the following statements about avibactam is correct?

It is used in combination with ceftazidime for urinary tract infections. Signup and view all the answers

What is a key feature of first generation cephalosporins?

Less activity of the alcohol component Signup and view all the answers

Which modification is used to improve stability in first generation cephalosporins?

Changing the acetoxy group to a pyridinium group Signup and view all the answers

What is the role of the aminothiazole ring in third generation cephalosporins?

Enhances outer membrane penetration Signup and view all the answers

Which statement regarding fourth generation cephalosporins is correct?

They significantly improve outer membrane penetration. Signup and view all the answers

Which of the following is a characteristic of fifth generation cephalosporins?

They contain oximinocephalosporins. Signup and view all the answers

What is the unique feature of Dalbavancin that enhances its convenience for patients?

Once-a-week dosing Signup and view all the answers

Which organization was responsible for the initial decline of Oritavancin's approval in December 2008?

The FDA Signup and view all the answers

Which Gram-positive bacterial infection is Dalbavancin particularly noted for being effective against?

Methicillin-resistant Staphylococcus aureus (MRSA) Signup and view all the answers

In which year was Dalbavancin finally approved for use in the USA?

2015 Signup and view all the answers

Who acquired the development rights to Oritavancin in 2009?

The Medicine Company Signup and view all the answers

What is a primary factor influencing the activity of cephalosporins?

Affinity for the target enzyme Signup and view all the answers

What modification can enhance the oral availability of cephalosporins?

Incorporation of 3-methyl groups Signup and view all the answers

How does placing an oximino group at C-7 affect cephalosporins?

Increases their potency and broadens their spectrum of activity Signup and view all the answers

Which of the following statements about carbapenems is incorrect?

They are well-absorbed in the gastrointestinal tract Signup and view all the answers

Which class of β-lactamase enzymes includes classes A, C, and D?

Classes A, C, & D Signup and view all the answers

What structural feature distinguishes monobactams from other β-lactam antimicrobials?

Monocyclic β-lactam ring Signup and view all the answers

In terms of activity, how do monobactams compare to penicillins?

Different spectrum of activity against Gram-negative bacteria Signup and view all the answers

What characteristic is associated with thienamycin?

Low stability and broad activity range Signup and view all the answers

What is a characteristic of Amikacin compared to Gentamicin?

Better stability to enzymes Signup and view all the answers

What recent development occurred with Plazomicin in August 2018?

Approval for treatment of cUTIs Signup and view all the answers

Which mechanism is not associated with aminoglycoside resistance?

Mutation of antibiotic structure Signup and view all the answers

How do aminoglycosides primarily impair bacterial translation?

By blocking the ribosome's translational machinery Signup and view all the answers

What is the primary reason for the effectiveness of aminoglycosides at slightly alkaline pH?

Positive charge improving absorption through membranes Signup and view all the answers

Which of these agents is indicated for oral use in animals since 1980?

Apramycin Signup and view all the answers

What is a common mechanism of action for aminoglycosides?

Impairment of bacterial translation Signup and view all the answers

Which mechanism is catalyzed by aminoglycoside-modifying enzymes (AMEs)?

Addition of ADP to hydroxyl groups Signup and view all the answers

What is a key characteristic of Cethromycin compared to traditional macrolides?

It has broader activity against Gram-positive bacteria. Signup and view all the answers

What allows for easier marketing approval of orphan drugs?

They are developed specifically for rare medical conditions. Signup and view all the answers

Which of the following statements about Linezolid is accurate?

It inhibits the formation of the 50S ribosomal subunit. Signup and view all the answers

What is a distinguishing feature of Solithromycin compared to Telithromycin?

It has improved metabolic stability. Signup and view all the answers

What is the mechanism of action of fluoroquinolones?

They stabilize DNA-topoisomerase complexes to prevent replication. Signup and view all the answers

Which structural feature is specific to Cethromycin?

Presence of a cyclic carbamate group. Signup and view all the answers

How are newer derivatives of Oxazolidinones expected to differ from Linezolid?

They may have fewer side effects. Signup and view all the answers

What is a common application for proflavin?

Topical agent for skin infections. Signup and view all the answers

What characteristic sets Finafloxacin apart from earlier quinolone antibiotics?

It was developed to address issues from earlier generations. Signup and view all the answers

Which type of bacteria has proven resistance that Cethromycin is effective against?

Penicillin-, macrolide-, and fluoroquinolone-resistant bacteria. Signup and view all the answers

Study Notes

Antibacterial Agents (MSOP1016)

β-lactam antibiotics (part 2) and beyond will be covered.
The lecture will cover Cephalosporins, Carbapenems, Monobactams, β-lactamase inhibitors and clavulanic acid, and newer developments.
An introduction to medicinal chemistry will be referred to (ISBN: 9780198749691, Chapter 19).

Cephalosporins

Discovered in the 1940s by Giuseppe Brotzu.
Structure resembles penicillins.
β-lactam ring fused to a 6-membered dihydrothiazine ring.
Key intermediate: 7-aminocephalosporinic acid (7-ACA).
7-Aminoadipic side chain.
Synthesis: Chemical hydrolysis of cephalosporin C.
Classification into generations based on spectrum of activity, chemical sophistication and chronology.
First generation examples: Cephalothin, Cephaloridine, Cefalexin, Cefazolin.
First generation issues: Less active alcohol form, but acetoxy groups are crucial to the mechanism of action; acid and alcohol can react to make a lactone.
First generation development to improve esterase stability: Changing the acetoxy group to a pyridinium group.
Subsequent developments (2nd generation) include methoxy groups at position 7 to stabilize neighboring carbonyl groups.
Oximinocephalosporins (second generation).
Further modification at position 3 led to variation in pharmacokinetics.
Fourth generation examples: Cefepime and Cefpirome.
Fifth generation examples: Ceftaroline fosamil and Ceftolozane.

Carbapenems

Example: Thienamycin (Merck, 1976).
Potent and broad-spectrum activity, low toxicity.
High resistance to β-lactamases.
Poor stability and not absorbed in the GI tract.
Different examples referenced: Imipenem, Meropenem and Ertapenem

Monobactams

Isolated from natural sources.
Monocyclic β-lactam ring.
Moderate activity in vitro against a narrow group of Gram-negative bacteria.
Active against P. aeruginosa.
Inactive against Gram-positive bacteria.
Different spectrum of activity compared to penicillins.

β-Lactamase Inhibitors

Two major classes: A, C & D (Ser-β-lactamases) and B (Metallo-β-lactamases).
Example: Clavulanic acid.
Isolated from Streptomyces clavuligerus.
Weak antibacterial activity.
Powerful, irreversible inhibitor of β-lactamases.
Used as a "sentry drug" for amoxicillin (Augmentin, co-amoxiclav).
Ticarcillin + clavulanic acid = Timentin.
Key structural features include strained β-lactam ring, enol ether, Z-configuration at C=C, no substituent at C-6 and R stereochemistry.
Mechanism of Action involves irreversible binding.
Example of penicillanic acid sulphones are sulbactam and tazobactam.
- Sulbactam: Broader spectrum but lower potency (used in IV preparation with ampicillin - Unasyn)
- Tazobactam: Broad spectrum and decent potency (in Tazosin/Zosyn, with piperacillin)
Newer example: Avibactam.
- Approved in 2015 for combination therapy with ceftazidime (UTIs), first new β-lactamase inhibitor in 20 years.
Another newer example is Relebactam.
Approved in 2019 for combination therapy with imipenem/cilastatin.

Cycloserine

A miscellaneous cell wall synthesis inhibitor.
Used in the treatment of Gram-positive (G+) infections.

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Description

Test your knowledge on the various subclasses of metallo-β-lactamases and their interactions with antibiotics like clavulanic acid and cephalosporins. This quiz covers the structure-activity relationships, characteristics of different generations of cephalosporins, and the role of novel antibiotics like Dalbavancin. Get ready to dive into the intricacies of antibiotic mechanisms and their clinical implications.