Antibiotics and Beta-Lactamase Quiz

The first generation of cephalosporins was marked by the introduction of key drugs like cephalothin and cephaloridine.

Cephalothin, a prominent member of the first generation, faced limitations due to its acetoxy group's importance in the mode of action and the less active alcohol.

To improve stability, the acetoxy group was replaced with a pyridinium group, leading to cephaloridine. This change, however, didn't significantly improve absorption.

Second generation cephalosporins distinguished themselves by the introduction of cephamycins, characterized by a methoxy group at position 7, and oximinocephalosporins, which enhanced stability against beta-lactamase enzymes.

Third generation cephalosporins incorporated an aminothiazole ring, enhancing their penetration through the outer membranes of Gram-negative bacteria. Modifications at position 3 influenced their pharmacokinetics.

Cephalosporins are a class of antibiotics that work by inhibiting the synthesis of bacterial cell walls. They have a strained beta-lactam ring fused to a dihydrothiazine ring.

The activity of each type of cephalosporin depends on its ability to reach the bacterial transpeptidase, its stability to beta-lactamases present, and its affinity for the target enzyme.

1st generation cephalosporins are more stable against acid and beta-lactamases than penicillins, but they have poor oral availability and lower activity. Variation in the 7-acylamino side chain alters activity.

Metabolic deacetylation of cephalosporins can lower their activity. This can be blocked by using metabolically stable groups. Adding a methoxy group at C-7 creates a new generation of cephalosporins with increased potency and a broader spectrum of activity.

Carbapenems are a class of antibiotics that have a very broad spectrum of activity and are highly resistant to beta-lactamases. However, they are not absorbed in the GI tract.

Monobactams are a class of antibiotics that have a monocyclic beta-lactam ring, a moderate activity in vitro against a narrow group of gram-negative bacteria, are active against P.aeruginosa, and inactive against gram-positive bacteria.

Beta-lactamase enzymes are a group of enzymes that can break down beta-lactam antibiotics, rendering them ineffective.

Beta-lactamase inhibitors are drugs that inhibit the activity of beta-lactamase enzymes, allowing beta-lactam antibiotics to work more effectively.

A group of enzymes that cleave the -lactam ring in antibiotics, rendering them ineffective. They are a major source of resistance to -lactam antibiotics.

A class of antibiotics that are potent inhibitors of -lactamases, but have weak antibacterial activity on their own. They function by forming a stable, inactive complex with the enzyme, preventing bacterial resistance.

A -lactamase inhibitor that was isolated from the bacterium Streptomyces clavuligerus. It is often used in combination with amoxicillin (Augmentin) or ticarcillin (Timentin) to broaden their antibacterial spectrum.

A group of -lactamase inhibitors that contain a sulphone group and are very effective against a wide variety of bacteria. Important examples include sulbactam and tazobactam.

A new type of -lactamase inhibitor that has recently been approved for use in combination with ceftazidime. It works by a different mechanism than clavulanic acid and sulbactam, helping to tackle multidrug resistant bacteria.

Dalbavancin was facing delays in getting FDA approval due to needing more data.

Durata Therapeutics acquired the rights to Dalbavancin from Pfizer in 2009, after Pfizer withdrew its marketing applications.

Dalbavancin's unique features, like once-a-week dosing and a short infusion time, make it a promising treatment option for skin infections.

Dalbavancin's development was marked by a second Phase 3 clinical trial for the treatment of acute bacterial skin and skin structure infections (abSSSI) beginning in 2011, with results expected in 2013.

After a long development process, Dalbavancin was finally approved for use in both the U.S. and Europe in 2015, becoming available under the brand names Dalvance® and XYDALBA® respectively.

A group of antibiotics that work by interfering with the process of protein synthesis in bacteria, specifically by binding to the 30S ribosomal subunit, disrupting the interaction between mRNA and tRNA.

They have good stability against bacterial enzymes, making them a second-line defense against multi-drug-resistant tuberculosis (MDRTB).

A class of enzymes produced by bacteria that modify the structure of aminoglycosides to make them ineffective.

The process by which bacteria develop resistance to aminoglycosides by changing the structure of their outer membrane.

A drug that can be used to treat complicated urinary tract infections (cUTIs), but only in patients without other treatment options.

A potential new aminoglycoside that was licensed for oral use in animals but has shown signs of resistance.

A mechanism of aminoglycoside resistance where bacteria develop more efficient pumps to expel the drugs from their cells.

The process by which aminoglycosides are actively transported across the bacterial cell membrane.

Ketolides are a class of antibiotics related to macrolides, but with structural modifications to improve activity and resistance profile.

Telithromycin is a ketolide, with modifications like OMe at position 6 and a cyclic carbamate at position 12, targeting bacterial ribosomes.

Cethromycin, another ketolide, has enhanced in vitro potency and broader activity against Gram-positive bacteria compared to macrolides. It's also effective against resistant strains and has potential for biodefense applications.

Cethromycin is being investigated for prophylactic treatment of anthrax post-exposure, showcasing its biodefense potential. The FDA granted it orphan drug status for this indication, facilitating its development.

Solithromycin is a novel ketolide undergoing Phase III trials, with structural modifications like a triazole, aminobenzene, and fluorine, contributing to improved stability and bioavailability.

Linzolid, an oxazolidinone, is a relatively new class of antibiotics that reached the market in 2000. Its unique mechanism of action and effectiveness against resistant strains led to its significant market success.

Oxazolidinones bind to the 50S subunit of bacterial ribosomes, preventing its combination with the 30S subunit and inhibiting protein synthesis. This unique mechanism allows for effectiveness against resistant strains.

Oxazolidinones primarily interact via Vander Waals interactions and p-p stacking with the ribosome. The acetamide group also forms hydrogen bonds with the RNA backbone, further stabilizing the interaction.

Newer oxazolidinones, like tedizolid and radezolid, offer improved potency and additional interactions with the ribosome, expanding their therapeutic applications.

Fluoroquinolones, a class of antibiotics, were introduced with nalidixic acid, followed by breakthroughs with ciprofloxacin and others. They are known for their potent activity against Gram-negative bacteria.