Antimicrobial Drugs

Flashcards covering the history, mechanisms of action, drug classes, resistance mechanisms, and effectiveness testing of antimicrobial agents based on the Chapter 14 lecture notes.

Chemotherapy

Drugs that target living cells and tissues, including pathogenic microbes.

Paul Ehrlich

The scientist who screened over $600$ arsenic compounds in the early $1900\text{s}$ to find a cure for syphilis ($Treponema\,pallidum$) without harming the host, establishing modern drug discovery techniques.

Prontosil

A synthetic dye discovered by Josef Klarer, Fritz Mietzsch, and Gerhard Domagk used to treat streptococcal infections; it was the first synthetic antimicrobial.

Alexander Fleming

The scientist who accidentally discovered penicillin, the first natural antibiotic, from $Penicillium\,notatum$ growing on a bacterial culture plate of Staphylococci in $1928$.

Dorothy Hodgkin

The scientist who used X-rays in the $1940\text{s}$ to analyze the structural chemistry of penicillin, enabling the creation of semisynthetic penicillins.

Selman Waksman

The researcher who studied soil microbes in the $1940\text{s}$ and discovered several antimicrobials, noting that Actinomycetes are the source of more than $50\%$ of natural antibiotics.

Bacteriostatic

An antibacterial property or drug action that reversibly inhibits bacterial growth without killing the cells.

Bactericidal

An antibacterial property or drug action that directly kills the target bacteria.

Broad-spectrum Drug

An antimicrobial drug that targets a wide variety of microbial pathogens, which can increase the risk of causing a superinfection.

Narrow-spectrum Drug

An antimicrobial drug that targets only a specific subset or group of microbial pathogens.

Superinfection

A secondary infection that develops when a broad-spectrum antimicrobial kills protective nonresistant normal microbiota, allowing drug-resistant pathogens to proliferate.

Synergistic Interaction

An interaction between two drugs administered together that produces an enhanced therapeutic benefit compared to either drug given alone, such as Trimethoprim and Sulfamethoxazole.

Antagonistic Interaction

An interaction between two drugs where one decreases the efficacy or increases the toxicity of the other, such as Rifampin decreasing the effectiveness of oral contraceptives.

Selective Toxicity

The property of an antimicrobial drug that allows it to selectively kill or inhibit the microbial pathogen while causing minimal or no harm to the host.

$\beta$-lactams

A major class of cell wall synthesis inhibitors characterized by a $\beta$-lactam ring that blocks the transpeptidase cross-linking of peptide chains in peptidoglycan.

Penicillins

A class of natural and semisynthetic $\beta$-lactam antibiotics derived from fungi that mainly target Gram-positive bacteria and a few Gram-negative bacteria.

Cephalosporins

A group of $\beta$-lactam antibiotics structurally similar to penicillins that resist $\beta$-lactamase enzymatic degradation and offer broader Gram-negative coverage across successive generations.

Carbapenems

Semisynthetic $\beta$-lactam antibiotics (such as imipenem, meropenem, and doripenem) that possess the broadest spectrum of activity against Gram-positive and Gram-negative bacteria.

Monobactams

Semisynthetic $\beta$-lactam antibiotics (such as aztreonam) that feature a single isolated ring structure and exhibit a narrow spectrum of activity against Gram-negative bacteria.

Vancomycin

A natural glycopeptide antibiotic that binds directly to the peptide end of peptidoglycan subunits, blocking transglycosylation and transpeptidation in Gram-positive bacteria.

Bacitracin

A natural peptide antibiotic derived from $Bacillus\,subtilis$ that blocks the transport of peptidoglycan precursors across the cytoplasmic membrane.

Aminoglycosides

Bactericidal antibiotics (such as streptomycin, gentamicin, neomycin, and kanamycin) that bind to the $30\text{S}$ ribosomal subunit, causing mRNA misreading and production of faulty proteins.

Tetracyclines

Broad-spectrum bacteriostatic antibiotics (such as tetracycline, doxycycline, and tigecycline) that bind to the $30\text{S}$ ribosomal subunit and block the attachment of tRNA to the mRNA-ribosome complex.

Macrolides

Broad-spectrum bacteriostatic antibiotics (such as erythromycin, azithromycin, and telithromycin) that bind to the $50\text{S}$ ribosomal subunit and inhibit peptide bond formation.

Lincosamides

Narrow-spectrum bacteriostatic antibiotics (such as lincomycin and clindamycin) that bind to the $50\text{S}$ ribosomal subunit to prevent peptide bond formation, particularly against streptococcal and staphylococcal infections.

Chloramphenicol

A broad-spectrum bacteriostatic antibiotic that binds to the $50\text{S}$ ribosomal subunit and prevents peptide bond synthesis, whose clinical use is limited due to severe toxicity.

Oxazolidinones

Synthetic broad-spectrum bacteriostatic drugs (such as linezolid) that bind to the $50\text{S}$ ribosomal subunit and prevent the formation of the initiation complex with the $30\text{S}$ subunit.

Polymyxins

Lipophilic peptide antibiotics (such as polymyxin B and colistin) that bind to lipopolysaccharide (LPS) in Gram-negative outer membranes, disrupting membrane integrity.

Daptomycin

A cyclic lipopeptide antibiotic that inserts into the cytoplasmic membrane of Gram-positive bacteria, causing membrane disruption and rapid cell death.

Metronidazole

A broad-spectrum bactericidal drug that interferes with DNA replication in anaerobic bacteria and protozoan parasites.

Rifampin

A narrow-spectrum rifamycin antibiotic that binds to bacterial RNA polymerase to inhibit transcription, frequently used in combination therapy against $Mycobacterium\,tuberculosis$.

Fluoroquinolones

Broad-spectrum bactericidal synthetic drugs (such as ciprofloxacin, ofloxacin, and moxifloxacin) that inhibit bacterial DNA gyrase, blocking DNA replication.

Antimetabolites

Antimicrobial compounds that function as competitive inhibitors for essential bacterial enzymes, halting specific metabolic pathways.

Sulfonamides

Synthetic broad-spectrum antimetabolite drugs (such as sulfamethoxazole) that competitively inhibit the enzyme involved in converting PABA into dihydrofolic acid.

Trimethoprim

A broad-spectrum antimetabolite drug that competitively inhibits dihydrofolate reductase, preventing the conversion of dihydrofolic acid to tetrahydrofolic acid.

Isoniazid

A narrow-spectrum antimetabolite drug that specifically targets $Mycobacterium$ species by blocking the synthesis of mycolic acid.

Diarylquinolines

A class of antimycobacterial drugs that inhibits bacterial ATP synthase, depleting available cellular ATP.

Imidazoles

Synthetic antifungal agents (such as miconazole, ketoconazole, and clotrimazole) that inhibit ergosterol biosynthesis to treat fungal skin and vaginal yeast infections.

Triazoles

Antifungal drugs (such as fluconazole) that inhibit ergosterol synthesis to treat systemic fungal infections, oral thrush, and cryptococcal meningitis.

Polyenes

Antifungal drugs (such as nystatin and amphotericin B) that bind directly to ergosterol in fungal cell membranes, forming pores that disrupt membrane permeability.

Echinocandins

Antifungal drugs (such as caspofungin) that inhibit the synthesis of $\beta(1\rightarrow 3)$ glucans in the fungal cell wall, often called 'penicillin for fungi'.

Griseofulvin

An antifungal drug that disrupts fungal cell division by interfering with microtubules and mitotic spindle assembly.

Atovaquone

An antimetabolite drug that inhibits electron transport in fungal and protozoal mitochondria, used to treat malaria, babesiosis, and toxoplasmosis.

Quinolines

Antiprotozoal drugs (such as chloroquine, mepacrine, and mefloquine) that inhibit heme detoxification in malaria parasites.

Avermectins

Antihelminthic drugs (such as ivermectin) that block invertebrate neuronal transmission, causing paralysis, starvation, and death.

Benzimidazoles

Broad-spectrum antihelminthic drugs (such as mebendazole and albendazole) that inhibit microtubule formation and reduce glucose uptake in parasitic worms.

Acyclovir

A nucleoside analog antiviral drug that is converted into its active form by viral enzymes and selectively inhibits viral DNA polymerase to terminate viral DNA chain elongation.

Amantadine and Rimantadine

Antiviral drugs that bind to the M2 protein ion channel of influenza A virus, preventing viral uncoating and escape from endosomes.

Antiretroviral Therapy (ART)

A combination drug treatment approach for HIV that utilizes multiple classes of antivirals (including reverse transcriptase, protease, integrase, and fusion inhibitors) to prevent resistance.

ESKAPE Pathogens

Six bacterial pathogens ($Enterococcus\,faecium$, $Staphylococcus\,aureus$, $Klebsiella\,pneumoniae$, $Acinetobacter\,baumannii$, $Pseudomonas\,aeruginosa$, and $Enterobacter$ spp.) notorious for multidrug resistance and hospital-acquired infections.

MRSA

Methicillin-resistant $Staphylococcus\,aureus$, a strain resistant to all $\beta$-lactams due to the acquisition of a novel low-affinity penicillin-binding protein (PBP).

VRSA

Vancomycin-resistant $Staphylococcus\,aureus$, a pathogen that acquired resistance to vancomycin via horizontal gene transfer from vancomycin-resistant enterococci (VRE).

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

Plasmid-encoded enzymes produced by bacteria that hydrolyze penicillins, cephalosporins, monobactams, and $\beta$-lactamase inhibitors, but not carbapenems.

MDR-TB

Multidrug-resistant $Mycobacterium\,tuberculosis$, defined as strains resistant to both first-line drugs rifampin and isoniazid.

XDR-TB

Extensively drug-resistant $Mycobacterium\,tuberculosis$, defined as MDR-TB strains that are additionally resistant to any fluoroquinolone and at least one second-line injectable drug.

Kirby-Bauer Disk Diffusion Test

A standardized assay used to measure bacterial susceptibility to antimicrobial drugs by observing zones of inhibition around drug-impregnated paper disks on agar.

Minimal Inhibitory Concentration (MIC)

The lowest concentration of an antimicrobial drug that prevents visible growth of a specific bacterial strain in vitro.

Minimal Bactericidal Concentration (MBC)

The lowest concentration of an antimicrobial drug required to kill $\ge 99.9\%$ of the initial bacterial population.

Etest

An antimicrobial susceptibility test combining disk diffusion and dilution methods using a plastic strip with a predefined antibiotic gradient placed on an inoculated agar plate.