β-Lactam Antibiotics Quiz

Cell Wall Inhibitors

• Penicillins are a class of antibiotics
• Cephalosporins are a class of antibiotics closely related to penicillins
• Carbapenems are synthetic beta-lactam antibiotics
• Monobactams are unique beta-lactam antibiotics
• Penicillins: Basic structure consists of a core four-membered beta-lactam ring attached to a thiazolidine ring and an R side chain. Structure varies based on the R substituent
• Penicillins: Nature of the side chain affects antimicrobial spectrum, stability against stomach acid, cross hypersensitivity, and susceptibility to beta-lactamases
• Mechanism of Action: Interfere with the last step of bacterial cell wall synthesis (transpeptidation). Structurally resemble the terminal portion of peptidoglycan. They compete for and bind to enzymes (PBPs) which catalyze transpeptidase and facilitate cross-linking of the cell wall
• Mechanism of Action: Lead to formation of a weakened cell wall and cell death. Penicillins are bactericidal acting in a time-dependent fashion
• Antibacterial Spectrum: Factors affecting PBP susceptibility include size, charge, and hydrophobicity
• Antibacterial Spectrum: Gram-positive microorganisms have cell walls that are easily traversed by penicillins, making them susceptible to these drugs
• Antibacterial Spectrum: Gram-negative microorganisms have an outer lipopolysaccharide membrane surrounding the cell wall, creating a barrier for the water-soluble penicillins
• Antibacterial Spectrum: Porins act as water-filled channels in the gram-negative membrane, permitting transmembrane entry of the water-soluble penicillin
• Natural Penicillins: Penicillin G and penicillin V are obtained from fermentations of Penicillium chrysogenum. Penicillin G has activity against various gram-positive and gram-negative organisms and spirochetes
• Natural Penicillins: Penicillin G potency is 5-10 times greater than penicillin V against Neisseria spp and anaerobes
• Natural Penicillins: Most streptococci are very sensitive to penicillin G; rising penicillin-resistant strains (especially S. pneumoniae and viridans streptococci) are emerging
• Natural Penicillins: A majority of Staphylococcus aureus are penicillinase producing, and resistant to penicillin G; penicillin remains the drug of choice for gas gangrene and syphilis
• Natural Penicillins: Penicillin V is orally available and has a spectrum similar to penicillin G, but its use for severe infections is limited; being more acid-stable than penicillin G
• Semisynthetic Penicillins: Ampicillin and amoxicillin, also known as aminopenicillins, or extended-spectrum penicillins are created by chemically attaching different R groups to the 6-aminopenicillanic acid nucleus.
• Semisynthetic Penicillins: Addition of R groups extends gram-negative antimicrobial activity to species like Escherichia coli, H. influenzae, and P. mirabilis
• Semisynthetic Penicillins: Ampicillin (with or without gentamicin) is the drug of choice for Listeria monocytogenes and susceptible Enterococcal species
• Antimicrobial/Adverse Reactions: Widely used in respiratory infections prophylactically by dentists in high-risk patients to prevent bacterial endocarditis
• Antimicrobial/Adverse Reactions: Penicillins are generally considered very safe, however, allergic reactions range from rashes to anaphylaxis and cross-allergic reactions are possible among beta-lactams
• Antimicrobial/Adverse Reactions: Diarrhea and pseudomembranous colitis related to C. difficile is a common problem
• Antimicrobial/Adverse Reactions: Nephritis is particularly observed with methicillin; Neurotoxicity via seizures are possible with high (intathecal or IV) doses of certain beta-lactams

Resistance to beta-lactam antibiotics

• Beta-lactamase production (hydrolyzes beta-lactam ring, loss of activity). Resistance caused by constitutive, chromosomal production, or by acquired plasmids
• Decreased permeability to the drug; gram-positive are less affected than gram-negative, which have complex cell walls and efflux pumps
• Altered PBPs; altered affinity for beta-lactam antibiotics; explains MRSA resistance

Cephalosporins

• Beta-lactam antibiotics closely related to penicillins
• Most cephalosporins are produced semisynthetically by chemical attachment of side chains to 7-aminocephalosporanic acid
• Structural changes in the acyl side chain alter antibacterial activity; variations at the 3-position modify the pharmacokinetic profile
• Cephalosporins have similar mechanisms of action to penicillins and experience the same resistance mechanisms as penicillins

Classification of Cephalosporins (Antibacterial Spectrum)

• Classified based on susceptibility patterns and resistance to beta-lactamases (First, Second, Third, Fourth and Advanced generation)

Other beta-Lactam Antibiotics

Carbapenems

• Synthetic beta-lactam antibiotics; differs from penicillins in that the sulfur atom in the thiazolidine ring is replaced with a carbon atom
• Imipenem, meropenem, doripenem, and ertapenem are carbapenems
• Imipenem resists hydrolysis by most beta-lactamases (except metallo-beta-lactamases)
• Meropenem and doripenem have similar activity to imipenem
• Ertapenem does not cover P. aeruginosa, certain enterococcus and acinetobacter species

Monobactams

• Unique; beta-lactam ring not fused to another ring
• Aztreonam is the only commercially available monobactam
• Primarily active against gram-negative pathogens like Enterobacteriaceae and P. aeruginosa
• Does not cover gram-positive or anaerobic bacteria

Beta-lactamase inhibitors

• Contain beta-lactam ring but do not possess significant antibacterial activity when administered alone
• Combination with other beta-lactam antibiotics overcomes hydrolysis from beta-lactamases
• Clavulanic acid is widely used as a beta-lactamase inhibitor

Fosfomycin

• Bactericidal, synthetic derivative of phosphonic acid
• Blocks cell wall synthesis by inhibiting enolpyruvyl transferase
• Primarily for UTI treatments caused by E. coli or E. faecalis

Polymyxins

• Cation polypeptides disrupting cell membrane integrity (to leakage)
• Bactericidal and concentration-dependent
• Primary activity against most clinically important gram-negative bacteria including P. aeruginosa, E. coli, K. pneumoniae, Acinetobacter spp., and Enterobacter spp.

Vancomycin

• Tricyclic glycopeptide active against certain aerobic and anaerobic Gram-positive bacteria (including MRSA, MRSE, Enterococcus spp, and C. difficile)
• Binds to peptidoglycan precursors, disrupting polymerization, cross-linking, and maintenance of cell wall
• Often used in patients showing skin and soft tissue infections, infective endocarditis, and nosocomial pneumonia

Lipoglycopeptides

• Bactericidal concentration-dependent antibiotic agents
• More potent than vancomycin and sometimes effective against vancomycin-resistant isolates
• Disrupts cell wall synthesise, and may disrupt membrane potential
• Telavancin is an alternative to vancomycin for skin and soft tissue infections, also for hospital-acquired pneumonia
• Oritavancin and dalbavancin have longer half-lives than telavancin, permitting administration on a single-dose and allowing treatment of ABSSSI (Acute bacterial skin and skin structure infections)
• Adverse effect profile includes nephrotoxicity and interactions with other OTC medications

Daptomycin

• Bactericidal concentration-dependent cyclic lipopeptide antibiotic
• Alternative for infections by vancomycin or linezolid for infections caused by resistant gram-positive organisms
• Inactivated by pulmonary surfactants, so is not useful in treating pneumonia
• Requires IV administration

Pharmacokinetics

• Detailed information concerning administration, routes, depot forms, absorption, distribution, metabolism, and excretion of different antibiotic classes are provided throughout the document

Adverse Effects

• Safety profile of the different classes of antibiotics is described, with focus on reactions as hypersensitivity, diarrhea, nephritis, neurotoxicity and others.

Test your knowledge on β-lactam antibiotics and their mechanisms of action. This quiz covers topics including resistance in gram-positive and gram-negative bacteria, the effects of altered PBPs, route of administration, and the absorption characteristics of various penicillins. Enhance your understanding of antibiotic pharmacology and bacterial interactions.