Module11 Microbiology- AB

Goal of antimicrobial therapy

Administer a drug that destroys infectious host anddoesn’’t harm the host

selective toxicity

Kills a pathogen selectively, and works better on microbes that are less similar to the host

Broad Spectrum AB

Effective against more than one group of microbe, but can destroy normal flora and fauna

AB admin routes

Oral, injection, topical or IV

Bacterial Antibiotic Mechanisms

Targets CW synthesis, folic acid synthesis, nucleic acid synthesis, cell membrane structure/function protein synthesis

Penicillins (targets CW)

Block cross-linking of peptidoglycan and have thiazolidine ring, beta lactam ring and variable side chain

Natural penicillins

Targets gram positive cocci bacteria and some gram negative, but easily defeated by penicillinases

Semisynthetic penicillins

Modified side chains and are broader sprectrum but still don’t resist beta lactamase

Penicillinases

Also called beta lactamase, they cleave the beta lactam ring

Clavulanic acid

Inhibits beta lactamase to allow penicillins to work, and is typically added to AB

Cephalosporins (targets CW)

Beta lactam ring that can be altered, and has a similar action to penicillin but causes less allergic reactions

Carbapenems (targets CW)

Has a beta lactam ring and an be used if there is a penicillin allergy

AB LAST RESORT

Glycopeptides (targets CW)

No beta lactam ring, and is made of amino acids or a peptide chain, but must be given IV

Ex. Vancomycin, AB LAST RESORT

Sulfonamides or sulfa drugs (Targets Folic acid)

Synthetic drugs that commonly cause allergic reactions, but inhibit the enzyme DHPS, acting as a competitive inhibitor to bind to active site on enzyme so PABA substrate can’t bind

Quinolones (targets DNA rep)

High potency and very broad spectrum, readily absorbed from the intestine but causes seizures

Ex. Ciproflaxan (anthrax), xifaxan (travelers diarrhea)

Rifampin (RNA polymerase)

Inhibits RNA transcription and is used in a drug cocktail to avoid AB resistance

Polypeptide (Cell membrane target)

Binds to LPS, disrupts membrane and is a AB LAST RESORT

Ex. Polymyxin: causing kidney and neuro toxicity

Lipopeptide (targets cell membrane)

Daptomyocin

Aminoglycoside (targets protein synthesis)

Distorts the ribosome, causing a translation error and this is broad spectrum. All antibacterial like this block mRNA complex in ribosome.

Tetracyclines (targets protein synthesis)

Blocks protein assembly and is broad spectrum, but upsets the GI system and causes hard tissue deposition

Glycylcyclines (targets protein synthesis)

Blocks protein synthesis and is a newer semi-synthetic version of tetracyclines, used when there is resistance to those

Chloramphenicol (targets protein synthesis)

Blocks protein assembly, but is AB LAST RESORT because of aplastic anemias that occur

Erythromycin (Targets protein synthesis)

Blocks protein assembly and is broad spectrum, and has decreased toxicity

Antifungal Drugs

Eukaryotic organism, so most antibacterials won’t work, but these have difficult selective toxicity. They target cell walls, plasma membranes and microtubules

Enchinocanden (Antifungal- CW targets)

Targets beta glucan in the cell wall, similar to penicillin for bacteria

Polyenes (plasma membrane targeting- Antifungal)

this binds ergesterol (fungal cholesterol) and disrupts lipid structure to cause ion leakage

Ex. Amphotericin

Azoles (Antifungal targeting plasma membranes)

Inhibits ergesterol synthesis and is used for systemic/ topical mycoses

Ex. Imidazoles

Griseofulvin (microtubules inhibition- Antifungal )

Used for oral, systemic topical mycoses such as ringworm

Antiprotozoan Drugs

Most target the intracellular component, as protozoans have a membrane. The major problem is complex life cycle and similarity to host, interfering with selective toxicity

Quinine (anti malarial )

Widespread resistance of malaria, and falciparum is resistant to 5 other drug classes.

Ex. Artemisinin: potent/effective with some resistance

Nitazoxanide

Antiprotozoan used to kill intestinal amoeba (Cryptosporidium, Giardia)

Metronidazole

Damages DNA of protozoans (Giardia)

Melbendazole/ albendazole (Anti-helminth)

Used to treat nematode infections by blocking transport of material into the cell

Praziquantel (anti-helminth)

Treats trematode/tapeworm by targeting the membrane

Ivermectin (anti-helminth)

Treats nematode and heart worm by interfering with the parasite nervous system and muscle function

Antiviral Drugs

Human cell relied on for host and virus well being so Stox is hard. The major modes of action are blocking penetration, transcription and translation, and preventing maturation

Oseltamivir (anti-viral)

Inhibits influenza AB replication

Acyclovir

Disrupts herpes DNA polymerase

Ribavirin (antiviral)

Blocks RNA synthesis of respiratory infections

Remdesivir

Polymerase inhibitor in covid-19

Interferon

Decrease time of healing and compromise of some infections, decreasing cold and papilloma symptoms. Mainly treats hep C and HIV warts, AB LAST RESORT

Drug resistance

Microbe adaptation to tolerate antibiotic amounts, as microbial populations have great adaptability and versatility

Intrinsic resistance

Spontaneous mutation of microbe

Acquired Resistance

Acquires new gene through horizontal gene transfer, which is on an enzyme and happens quicker than other resistance.

How drug resistance is worsened

Human overuse of AB, global travel/globalization, over prescription for food sources and hospital factor