Ch 9. Antimicrobial Chemotherapy

Antimicrobial Chemotherapy

Use of drugs to treat infections caused by microbes.

Selective Toxicity

Ability to target pathogens without harming host cells.

Therapeutic Index

Ratio of toxic dose to therapeutic dose.

Minimal Inhibitory Concentration (MIC)

Lowest concentration preventing microbial growth.

Minimal Lethal Concentration (MLC)

Lowest concentration killing the microorganism.

Penicillin

First true antibiotic discovered by Alexander Fleming.

β-lactam Ring

Core structure in penicillin and cephalosporins.

Transpeptidation

Process crucial for bacterial cell wall synthesis.

Cephalosporins

Broad-spectrum antibiotics derived from Acremonium fungus.

Carbapenem

Hybrid drugs combining penicillin and cephalosporin properties.

Vancomycin

Narrow-spectrum antibiotic effective against Gram-positive bacteria.

Aminoglycosides

Bactericidal antibiotics binding to 30S ribosomal subunit.

Streptomycin

First antibiotic effective against tuberculosis (TB).

Sulfonamides

First synthetic antibiotics discovered by Domagk and Trefouel.

Prontosil Red

First sulfa drug effective against streptococcal infections.

Actinomycetes

Bacteria known for producing antibiotics like streptomycin.

Deep Learning in AI

Used to screen compounds for antimicrobial effectiveness.

MRSA

Methicillin-resistant Staphylococcus aureus, a drug-resistant bacterium.

Dilution Susceptibility Tests

Method to determine MIC of antimicrobial agents.

Disk Diffusion Test

Kirby-Bauer method for testing antibiotic effectiveness.

Etest

Method combining dilution and diffusion for MIC determination.

Narrow Spectrum Antibiotics

Effective against specific types of bacteria.

Broad Spectrum Antibiotics

Effective against a wide range of bacteria.

Aerobic Gram-negative

Includes Proteus, Escherichia, Klebsiella, Serratia.

Semisynthetic antibiotics

Modified versions of natural antibiotics.

Renal damage

Potential toxicity from certain antibiotics.

Tetracyclines

Bacteriostatic antibiotics targeting 30S ribosome subunit.

Broad-spectrum

Effective against a wide range of bacteria.

Oxytetracycline

Produced by Streptomyces spp., a tetracycline antibiotic.

Chlortetracycline

Another tetracycline from Streptomyces spp.

Doxycycline

Semisynthetic tetracycline antibiotic.

Black teeth

Side effect of tetracyclines due to calcium chelation.

Liver toxicity

Potential adverse effect of tetracyclines.

Macrolides

Bacteriostatic antibiotics binding to 50S ribosome subunit.

Erythromycin

True antibiotic from Saccharopolyspora, a macrolide.

Azithromycin

Macrolide used for chlamydia treatment, known as 'Z-pack'.

Amoxicillin

Commonly prescribed antibiotic alongside macrolides.

Lincosamides

Bacteriostatic antibiotics targeting 50S ribosome subunit.

Clindamycin

Lincosamide used to treat CA-MRSA infections.

C. difficile

Bacteria that can proliferate due to lincosamide use.

Oxazolidinones

Synthetic bacteriostatic drugs targeting 50S ribosome subunit.

Linezolid

Oxazolidinone effective against MRSA and VRE.

Chloramphenicol

First broad-spectrum antibiotic, binds to 50S ribosome.

Grey baby syndrome

Toxic reaction in infants from chloramphenicol.

Aplastic anemia

Serious side effect of chloramphenicol.

Neurotoxin reactions

Adverse effects associated with chloramphenicol.

Metabolic Antagonists

Act as antimetabolites to inhibit metabolic processes.

Structural Analogs

Molecules resembling others, affecting biological functions.

Bacteriostatic

Inhibits bacterial growth without killing bacteria.

PABA Analog

Mimics p-aminobenzoic acid to inhibit bacterial enzymes.

Dihydropteroate Synthase

Enzyme inhibited by sulfa drugs to block folate synthesis.

Trimethoprim

Synthetic antibiotic inhibiting dihydrofolate reductase.

Synergism

Combined effect of drugs enhancing therapeutic efficacy.

Side Effects of Trimethoprim

Includes abdominal pain and photosensitivity reactions.

Nucleic Acid Synthesis Inhibition

Mechanisms targeting RNA polymerase and topoisomerases.

Fluoroquinolones

Bacteriocidal drugs inhibiting DNA-gyrase and topoisomerase IV.

Ciprofloxacin

A fluoroquinolone effective against enteric bacteria.

Rifamycins

Bacteriocidal antibiotics blocking RNA transcription.

Rifampin

Most used rifamycin for treating TB and meningitis.

Red Sweat and Urine

Possible side effect of rifamycin use.

Antiviral Drugs

Inhibit virus-specific enzymes and life cycle processes.

Tamiflu

Neuraminidase inhibitor shortening influenza illness duration.

Xofluza

Blocks transcription in influenza viruses.

Resistant Viruses

Some viruses develop resistance to antiviral treatments.

Herpesviridae

DNA viruses using own enzymes for phosphorylation.

Acyclovir

Analog inhibiting herpesvirus replication.

Vidarabine

Another analog for herpesvirus replication inhibition.

NRTIs

Nucleoside inhibitors causing faulty DNA in HIV.

AZT

First NRTI used for HIV treatment.

NNRTIs

Prevent HIV DNA synthesis by blocking reverse transcriptase.

Protease inhibitors

Mimic peptide bonds targeted by HIV protease.

Integrase inhibitors

Prevent incorporation of HIV genome into host DNA.

Fusion inhibitors

Block HIV entry into host cells.

HAART

Combination therapy to prevent HIV drug resistance.

PrEP

Daily two NRTIs for HIV prevention.

Hepatitis C Virus

RNA virus with increased acute cases since 2010.

Interferon-α

Cytokine used in hepatitis C treatment.

Ribavirin

Antiviral drug used for hepatitis C.

Sofosbuvir-velpatasvir

Combination drug for hepatitis C (Epclusa).

Sofosbuvir-ledipasvir

Combination drug for hepatitis C (Harvoni).

Fungistatic

Drugs that inhibit fungal growth without killing.

Nystatin

Used to control superficial candidiasis.

Amphotericin B

Highly toxic polyene binding ergosterol in membranes.

5-flucytosine

Uracil analog disrupting RNA function in fungi.

Fluconazole

Low side effects, used prophylactically in immunocompromised.

Echinocandins

Inhibit β-1,3-D-glucan synthase in fungal cell walls.

Chloroquine

Antiprotozoal drug effective against Plasmodium.

Metronidazole

Activated by Entamoeba and Trichomonas for treatment.

Drug MIC

Minimum inhibitory concentration for effective drug levels.

Drug resistance

Microbial ability to withstand effects of drugs.

Resistance mechanisms

Methods microbes use to evade drug effects.

Overcoming resistance

Strategies include using multiple drugs and appropriate concentrations.