Antibacterial Agents

heat: boiling, autoclaving, dry heat, incineration, irradiation (UV and Gamma)

• ethylene oxide
• ozone
• low temperature gas plasma

antibiotics that can inhibit G(+) or G(-)

can only inhibit a certain genera

antibiotics that inhibit the growth of bacteria but do not kill

antibiotics that kill bacteria

the lowest antibiotic concentration that inhibits growth of bacteria is MIC when the antibiotic is exposed to serial drug dilutions

the lowest antibiotic concentration that kills 99.9% of the population is the MBC when exposed to a serial drug dilution

• kills many but not all organisms
• depending on method, can lead to low, intermediate, or high levels of disinfection

• heat
• low temp
• drying: most microbes cannot grow in low moisture environments
• irradiation
• chemicals

when combinations of two or more antibiotics have enhanced bactericidal activity when tested together compared to the drug on its own

when one antibiotic prevents another from working well

a bacterial enzyme that hydrolyzes the B-lactam ring in the B-lactam class of antibiotics, inactivating the drug

• gram negative: some antibiotics cannot cross outer membrane
• mycobacteria: are intrinsically resistance because of their cell wall structure

no

• cell wall synthesis
• protein synthesis
• nucleic acid synthesis
• central metabolism

• efflux pumps: pumping drug out of cell
• decreased uptake:
• inactivating enzyme before entry into cell
• inactivating enzyme after entry into the cell
• disrupting pathways with alternate enzymes
• mutations that prevent binding or activation of drug

• structure: B-lactam ring
• bactericidal
• mechanism of action: inhibit the action of peptidolgycan synthesis disrupting cell wall, by mimicking structure of amino acids to the cell wall.

• penicillins
• cephalosporins
• cephamycins
• carbapenems
• monobactams

• penicillin binding proteins (PBPs)
• called transpeptidases

• inactivation of the drug by B-lactamase enzyme
• G (-) cell wall blocks B-lactams from crossing
• PBPs gain mutation to prevent binding of B-lactam drug to active site

• vancomycin: inhibits cross linkage of peptidoglycan layers
• daptomycin: causes depolarization of cytoplasmic membrane, resulting in disruption of ionic concentration gradients
• bacitracin: inhibits bacterial cytoplasmic membrane and movement of peptidoglycan precursors
• polymyxins: inhibit bacterial membranes

• a glycopeptide
• bactericidal/bacteriostatic
• mechanism: disrupts peptidolycan synthesis in growing cells by inhibiting linkage of peptide chains by mimicking PBP substances
• resistance: occurs when bacteria change the peptides used in peptidolygcan cross bridges
• effectiveness: only to G(+)

• lipopeptide
• bactericidal
• mechanism of action: binds irreversibly to cytoplasmic membrane causing disruption of ionic gradients. Results to cell death
• effectiveness: only G(+)

• polypeptide mixture
• bactericidal/bacteriostatic
• mechanism of action: inhibits cell wall synthesis by interfering with the recycling of cell wall synthesis molecules
• effectiveness: G(+)

• bactericidal
• mechanism: inserts into bacterial membranes by interacting with LPS and phospholipids in the outer membrane, causes cell permeability and deth
• effectiveness: G(-)

reducing access to target molecules by changing cell surface molecules

• bactericidal
• mechanism:produce premature release of peptide chains from 30S ribosomes
• effectiveness: aerobes, G(-)

• increased expulsion of drugs from cell
• decreased uptake of drugs into cytoplasm
• enzymatic modification of drug preventing ribosomal binding
• mutation in 30S ribosomal binding site preventing drug activity

• bacteriostatic
• mechanism: prevents polypeptide elongation at 30s ribosome
• effectiveness: broad spectrum [ G(-), G(+), intracellular pathogens ]

• primary and most wide spread mechanism: expulsion of drugs from cells through efflux pumps
• enymatic modifcation of drug to prevent ribosomal binding
• decreased uptake of drugs into cytoplasm
• mutation in 30s ribosomal binding site, preventing drug activity

• bacteriostatic
• mechanism: prevents polypeptide elongation at 50s ribosome
• Effectiveness: broad spectrum against G(+)

primary resistance: methylation of 23S rRNA, preventing binding of drugs

• mechanism: binds to DNA topoisomerase, inhibting DNA replication, recombination, and repair
• broad spectrum: G(-) and G(+)

primary: chromosomal mutation in topoisomerase gene

• mechanism: inhibits transcription by binding to RNA polymerase
• effectiveness: G(+), mycobacteria
• used in combindation with other antimicrobials because resistance develops rapidly

mutations in RNA polymerase beta subunit that prevents drug binding

• mechanism: disrupts the folic acid synthesis pathway by inhibiting dihydropteroate synthase
• effectiveness: broad spectrum [ G(-) and G(+)]

bacteria that do not synthesize their own folic acid are intrinsically resistant

mechanism: inhibits dihydrofolate reductase and disrupts folic acid synthesis