Chapter 14 Antimicrobial Drugs

Broad-spectrum antibiotics

affect a a wide range of bacteria but can lead to resistant populations and superinfection.

Superinfection

loss of resident microbiota that reduces competition, allowing pathogens to thrive

Why do broad spectrum antibiotics cause resistant population?

they kill BOTH harmful and beneficial bacteria REDUCING COMPETITION, giving resistant bacteria a chance to thrive and reproduce → resistant population

If you lose microbiota,

competition for pathogen is released

Routes of administration and plasma concentration

• IV: MOST efficient for achieving high plasma concentration

• Oral administration: LESS effective but more AFFORDABLE

Drugs are

H+ → hydrophilic

Social effects of antibiotic use

• Overuse and misuse can lead to antibiotic resistance which affects public health

• Encourages the evolution of resistant strains like MRSA

Penicillins (Beta Lactam)

• Target: Penicillin-Binding Proteins (PBP’s)

• Interact directly with PBP’s and inhibit transpeptisase activity

Cephalosporins (Beta Lactam)

• Target: Penicillin-Binding Proteins (PBP’s)

• Prevents cell wall synthesis which leads to bacteria cell lysis

Monobactams (beta lactams)

• Target: Pencillin-Binding Proteins (PBP’s)

• Inhibits bacterial cell wall synthesis by binding to PBP’s leading to cell lysis

  • specifically effective against Gram - bacteria and are resistant to many beta-lactamases

Carbapanems (Beta Lactam)

• Target: Penicillin-Binding Proteins (PBP’s)

• Inhibits cell wall synthesis, leading to bacteria death

Methicillin (Beta Lactam)

• Target: Penicillin-Binding Proteins (PBP’s)

• Inhibits bacterial cell wall synthesis, but some bacteria have evolved RESISTANCE through production of altered PBP’s

Beta Lactams

inhibit cell wall synthesis by targeting penicillin-binding proteins (PBP’s), preventing peptidoglycan cross-linking

Beta-lactamase

enzyme that some bacteria produce to resist beta lactam antibiotics by breaking down the beta-lactam ring

Glycopeptides

• Target: NAM and NAG

• Inhibit cell wall synthesis by binding to the substrate (peptide chain) of PBP’s

  • Used for MRSA

  • Resistance VRSA: bacteria evolved to CHANGE the shape of PBP’s so vancomycin can no longer bind

Bacitracin

• Target: Cell wall synthesis inhibitor

• Blocks cell wall precursors from being transported outside the cell

Metranidazole

breaks DNA strands (used for anaerobic infections)

Aminoglycosides

• Target: 30S ribosomal subunit

• Causes mismatches between codons and anticodons, leading to faulty proteins that insert into and disrupt cytoplasmic membrane

Tetracyclines

• Target: 30S ribosomal subunit

• Blocks association of tRNAs with ribosome

• Doxycycline used for chlamydia and rickettsia rickettsii

Macrolides, Licosamides, and Chloramphenicol

• Target: 50S ribosomal subunit

• Blocks peptide bond formation between amino acid

• Azithromycin used to treat Naegleria fowleri

Oxazolidinones

• Target: 50S ribosomal unit

• Interferes with formation of the initiation complex between 50S and 30S subunits and other factors

Sulfonamides (Antimetabolites)

• Target: enzyme #1 in the folic acid synthesis pathway

• Inhibits the enzyme involved in production of DIHYDROFOLIC acid

Trimethoprim (Antimethabolite)

• Target: enzyme #2 in the folic acid synthesis pathway

• Inhibits the enzyme involved in the production of TETRAHYDROFILIC ACID

Rifamycins

• Target: bacterial RNA polymerase (prokaryotic)

• Inhibits bacterial RNA polymerase activity and blocks TRANSCRIPTION, killing the cell

Fluoroquinolones

• Target: DNA gyrase

• Inhibits the activity of DNA gyrase and blocks DNA replication, killing the cell

  • Supercoiling is not prevented

Lipopeptide

• Target: bacterial cell membrane

• Inserts into the cytoplasmic membrane of gram + bacteria , disrupting the membrane and killing the cell

Polymyxins

• Target: Lipopolysaccharides in outer membrane of gram -

• Kills the cell through the eventual disruption of the outer membrane and cytoplasmic membrane

• Polymyxin B is in neosporin

Metronidazol binds to DNA causing

fragmentation of DNA

• bacteria dies over time

Polymyxins and daptomycin work by

making holes, water comes in → cell lyses

Cells are always in a

hypotonic solution

Beta lactams drawing

..

Vanocomycin is used in

MRSA (methicillin resistant staphylococcus auearas)

VRSA =

vancomycin resistant staphylococcus aueruas

PBP

enzymes in bacteria that help build cell wall by forming cross links

• give the cell wall strength and structure

Glycopeptides drawing

…

Bacitracin drawing

…..

Channel proteins

transfer NAG-NAM from inside the cell through plasma membrane

Bacitracin works by

blocking channel proteins

Bacteria needs folic acid to

do binary fission

• therefore disrupting their folic acid synthesis is a way to stop their growth

Sulfanomides & Trimethroprim drawing

….

Isoniazid

• Target: mycolic acid synthesis

• Interferes with the synthesis of mycolic acid

Imidazoles, Triazoles, Allymines (antifungal)

• Target: Ergosterol synthesis

• Inhibit ergosterol synthesis

Polyenes (antifungal)

• Target: Ergosterol in fungal cell membranes

• Bind ergosterol in the cell membranes and create pores that disrupt the membrane

Nikkomycin Z (antifungal)

• Target: Chitin synthesis

• Inhibits chitin synthesis which leads to weakened cell wall and fungal death

• Treats Coccidioidomyosis (Valley fever)

Acylovir (antiviral)

• Target: Viral DNA polymerase

• Nucleoside analog inhibition of nucleic acid synthesis (disrupt DNA and RNA)

  • Treats HSV I and II

Pleconoaril (antiviral)

• Target: viral capsid

• Inhibit viral uncoating

  • Treats Entrovirus infections

Ritonavir and Simeprevir (antiviral)

• Target: protease

• Inhibit protease

  • Ritonavir = HIV

  • Simeprevir = Hepatitis C

Raltegravir (antiviral)

• Target: Intergrase

• Inhibits of intergrase

  • HIV

Enfurvirtride (antiviral)

• Target: HIV gp41

• Inhibit membrane fusion

  • HIV

Acyclovir mimics

a G nucleotide

• DNA synthesis stops

AZT is the

1st anti HIV drug (reverse transcriptase inhibitor)

Methods of antibiotic resistance

• Efflux pump

• Blocked penetration

• Inactivation of enzymes

• Target modification

Disk diffusion

bigger zone of inhibition = more effective

E-test

where zone of inhibition touches the strip

• Higher = higher concentration

• Lower = lower concentration

• MIC = minimum inhibitory concentration

Tube dilution test

grow antibiotics in concentration and look for when it dies in the concentration

• turbid = does not kill

• not turbid = that’s the MIC

• looking for lowest concentration that kills bacteria