Cell Wall Synthesis Inhibitors: Beta-Lactams and Penicillins

Comprehensive vocabulary flashcards covering bacterial cell wall structure, inhibitors of cell wall synthesis, $$\beta$$-lactam classes, resistance mechanisms, $$\beta$$-lactamase groupings, and specific penicillin subclasses.

MRSA (Methicillin-Resistant Staphylococcus aureus)

Strains of Staphylococcus aureus that acquire resistance to almost all $\beta$-lactams (except 5th generation cephalosporins) via horizontal gene transfer of an altered transpeptidase (PBP2 to PBP2a).

Non-fermenting Gram-negative rods

Opportunistic Gram-negative bacilli requiring $O_2$ that cannot ferment sugars (such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia); they often display broad-spectrum resistance due to limited outer membrane diffusion.

Diaminopimelic acid (DAP)

An amino acid present in the stem peptide of Gram-negative peptidoglycan that directly participates in peptide cross-linking with D-alanine.

Penicillin Binding Proteins (PBPs)

Bacterial transpeptidase enzymes that catalyze the cross-linking of peptidoglycan chains; they serve as the primary targets bound and inactivated by $\beta$-lactam antibiotics.

$\beta$-Lactam Ring

A strained four-membered cyclic amide ring core shared by penicillins, cephalosporins, monobactams, and carbapenems that mimics the D-Ala-D-Ala terminus of peptidoglycan to acylate PBPs.

Fosfomycin

A cell wall synthesis inhibitor that acts in the bacterial cytoplasm by blocking the initial enzymatic step where phosphoenolpyruvate is added to UDP-NAG to form UDP-NAM.

Cycloserine

A cytoplasmic cell wall inhibitor that inhibits the synthesis and dimerization of D-alanine into D-Ala-D-Ala during pentapeptide precursor assembly.

Bacitracin

A topical cell wall synthesis inhibitor that interferes with the dephosphorylation and recycling of the lipid carrier pyrophosphate (bactoprenol) in the bacterial cell membrane.

Glycopeptides

A class of cell wall active antibiotics that bind directly to the terminal D-Ala-D-Ala peptide motifs of growing peptidoglycan chains outside the cell membrane, preventing cross-linking.

Porin Channel Alteration

A resistance mechanism in Gram-negative bacteria involving mutations that alter pore proteins or downregulate channel numbers, decreasing the influx of $\beta$-lactam antibiotics.

Metallo-$\beta$-lactamases (MBL)

Class B $\beta$-lactamases that contain a divalent cation in their active site and are inhibited by EDTA; they hydrolyze penicillins, cephalosporins, and carbapenems, but spare monobactams.

Extended-Spectrum $\beta$-Lactamases (ESBL)

Class A serine enzymes that hydrolyze penicillins, early cephalosporins, extended-spectrum cephalosporins, and monobactams, but generally do not degrade carbapenems.

AmpC $\beta$-lactamases

Class C serine cephalosporinases that confer resistance to penicillins, early cephalosporins, and extended-spectrum cephalosporins, and are poorly inhibited by traditional $\beta$-lactamase inhibitors.

Sulbactam

A traditional $\beta$-lactamase inhibitor that notably possesses direct, intrinsic antibacterial activity against Acinetobacter baumannii.

Diazabicyclooctanones (DBO)

A class of non-$\beta$-lactam $\beta$-lactamase inhibitors (e.g., avibactam) capable of inhibiting Class A, Class C (AmpC), and selected Class D enzymes.

Vaborbactam

A boronic acid derivative that functions as a new non-$\beta$-lactam $\beta$-lactamase inhibitor designed to target serine carbapenemases.

Benzathine Penicillin

A repository depot intramuscular formulation of penicillin G with prolonged duration of action, used primarily for syphilis and monthly prophylaxis of rheumatic heart disease (never given intravenously).

Anti-staphylococcal Penicillins

Penicillinase-resistant penicillins (nafcillin, oxacillin, cloxacillin, flucloxacillin, dicloxacillin) eliminated primarily by the liver, preferred for Methicillin-Susceptible Staphylococcus aureus (MSSA) infections due to faster bactericidal killing than vancomycin.

Ampicillin

An aminopenicillin with good CSF penetration and high urinary concentration; considered an essential first-line agent for Listeria monocytogenes infections.

Amoxicillin

An oral aminopenicillin characterized by superior gastrointestinal bioavailability compared to ampicillin and whose absorption is not decreased by food.

Ureidopenicillins

A subclass of anti-pseudomonal penicillins (including piperacillin, azlocillin, and mezlocillin) with enhanced activity against Pseudomonas aeruginosa and Gram-negative bacilli.

Piperacillin-Tazobactam

A broad-spectrum combination of an anti-pseudomonal ureidopenicillin and a $\beta$-lactamase inhibitor, indicated for severe nosocomial infections and anticipated polymicrobial aerobic/anaerobic infections.

Aztreonam

A monobactam antibiotic active exclusively against aerobic Gram-negative bacilli (including Pseudomonas aeruginosa); it resists metallo-$\beta$-lactamases and is safe for use in penicillin-allergic patients.

Probenecid

A competitive inhibitor of organic anion transporters in renal tubular cells that decreases the excretion of penicillins, thereby raising serum concentrations and prolonging their half-life.