Microbes + Antibiotics

What are the 3 main types of bacteria?

cocci, bacilli, spirilla

What are bacteria classified by?

cell wall properties

nutritional patterns

respiration

What is unique about viruses?

require host cell to replicate and live

What are the goals of antimicrobial drugs?

1. Disrupt the cell processes or structures of bacteria, fungi, and protozoa.

2. Inhibit virus replication

What 3 factors must be known for antimicrobial drugs to work?

nature of the micro-organism

micro-organisms susceptibility to drugs

medical condition of patient

What are the idea characteristics of an anti-microbial drug?

selective

microbicidal

doesn't cause resistance

remains active in human

does not cause allergies or harm to human health

What are the main targets of antibiotics?

1. protein synthesis

2. nucleic acid synthesis

3. cell wall synthesis

4. cell membrane function

5. pathways + metabolism

What is bacteriostatic?

inhibits bacterial growth

What does bacteriostatic drugs rely on?

host immunity

What is bactericidal?

kills bacteria

What are the pros/cons of a narrow spectrum drug?

pro: affects pathogen only

con: requires you to ID the pathogen

What are the pros/cons of broad-spectrum drugs?

Pro: works on wide range of organisms

Con: disrupts normal flora, leads to resistance

What are the general side effects of antimicrobial drugs?

allergic reaction

toxic effects to humans

suppression of normal flora

antimicrobial resistance

What are the causes of bacterial resistance?

chromosomal mutations

gene amplification

plasmids

What are the ways bacteria develop resistance to drugs?

1. drug inactivating enzymes (cleave molecule inactive)

2. alteration of abx target molecule

3. alter drug transporter to decrease uptake of drug

4. produce efflux pumps to eliminate drug

5. create new pathway when abx blocks original

What is the final step in bacterial cell wall synthesis?

peptidoglycan (PPG) cross linking, aka transpeptidation

What do B-lactams do?

block PPG crosslinking, therefore blocking cell wall synthesis

Which bacteria type are B-lactams more effective against?

gram +

Are B-lactams bactericidal or bacteriostatic?

bactericidal, but require bacteria to be actively dividing to work

What are examples of B-lactams?

PCNs

Cephalosporins

Carbapenems

Monobactams

Why does B-lactams structure cause bacterial resistance?

B-lactamase can open the B-lactam ring, therefore inactivating the drug

What are the difference PCN drug classes?

Natural: PCN

Aminopenicillins: Amoxicillin

Penicillinase resistant

extended spectrum

What is clavulanate?

beta lactamase inhibitor

What is Augmentin? What is the benefit?

Amoxicillin + Clavulanate

inhibits beta lactamase so no resistance

How are PCNs excreted?

via renal tubule

What is probenecid (Benemid) and what is it used for?

blocks tubular secretion of PCN

prolongs PCN action

What is the DOC for syphilis?

PCN

What are examples of cephalosporins?

Cephalexin (Keflex)

Cefdinir (Omnicef)

Ceftaroline

What is a first gen cephalosporin?

Cephalexin (Keflex)

What bacteria is Cephalexin (Keflex) effective against?

gram +

What is the benefit of using a third + fifth gen cephalosporin?

wider spectrum and beta lactamase resistant

What is an example of a 3rd gen cephalosporin?

Cefdinir (omnicef)

What is Cefdinir (omnicet) used for?

prophylaxis

treat infections in hospitalized patients

What is an example of next/5th gen cephalosporin?

Ceftraroline

What type of bacteria is Ceftraroline effective against?

MRSA

gram +

some gram -

What are the main side effects of cephalosporins?

allergy

vit K deficiency --> increased bleeding

seizures

What is an example of a monobactam?

Aztreonam (Azactam)

Aztreonam (Azactam) is what type of drug?

monobactam

What bacteria is Aztreonam (Azactam) effective against?

only aerobic gram - (neisseria, pseudomonas)

What is a benefit of monobactams/Aztreonam (Azactam)??

highly resistant to B-lacatmase

What is Aztreonam (Azactam) used for?

PCN allergic patients

What are the side effects of Aztreonam (Azactam)??

rash

liver problems

What is the greatest potency and broadest spectrum of all beta lactase?

Carbapenems: Primaxin IV

Is Primaxin IV (a carbapenem) beta-lactamamse resistant?

yes

What are carapenems (ex: primaxin IV) used for?

infection resistant to other drugs

Why is imipenem combined with cilastatin? (to make Primaxin IV)

impenem is metabolized in kidney to a toxic metabolite

Cilastin inhibits the toxic metabolite formation

What is Vancomycin used for?

gram +

MRSA

when pts are allergic to B-lactams

What is an example of a glycopeptide?

Vancomycin

What kind of drug is Vancomycin?

Glycopeptide

What is the MOA of vancomycin?

inhibits PPG crosslinking, therefore inhibiting cell wall synthesis

Is vancomycin bactericidal or bacteriostatic?

bactericidal

How is vancomycin administered? Why?

IV

poor oral absorption

What are the side effects of vancomycin?

flushing

nephrotoxicity

ototoxicity

hypotension

hypersensitivity

What is the MOA of bacitracin?

prevents PPG transport, therefore inhibits cell wall synthesis

What is the spectrum of bacitracin?

narrow, gram +

How is bacitracin administered? Why?

topical, because it is nephrotoxic systemically

What makes up Neosporin?

bacitracin + polymyxin B + neomycin

What is the MOA of fosfomycin (Fosomin)?

inhibits PPG synthesis therefore inhibits cell wall synthesis

Is fosfomycin bactericidal or bacteriostatic?

bactericidal

What is fosfomycin used for?

UTIs

What kind of bacteria is fosfomycin effective for?

gram + and gram -

How does bacteria develop resistance to fosfomycin?

bacterial blocks transport of drug into cell

What is the structure of polymyxins?

lipophobic head and lipophilic tail

What is the MOA of polymyxins?

disrupt cel membrane

Are polymyxins bacteriostatic or bactericidal?

bactericidal

What type of bacteria are polymyxins effective against? Why?

gram -

they have thick cell membranes

What are polymyxins used for?

with other abx or steroids for skin or eye lesions

What are the side effects of systemic polymyxin use?

neurotoxicity and nephrotoxicity

What antibiotics affect cell membrane permeability?

polymyxins

gramicidin

daptomycin (Cubicin)

What is the MOA of gramicidin?

creates pore in bacterial membrane

Gram + bacteria components

thick peptidoglycan cell wall

plasma membrane underneath

Gram - bacteria components

outer cell membrane

peptidoglycan cell wall

plasma membrane

What type of bacteria do gramicidin affect?

mostly gram +

is gramicidin bactericidal or bacteriostatic?

bactericidal

How is Gramicidin administered? Why?

topically, systemically causes hemolysis

When is Gramicidin used for ocular use?

when mixed with polymyxin B or neomycin

What is gramicidin used for?

medical lozenges for sore throat

infected wounds

What is the MOA of Daptomycin (Cubicin)?

inserts lipophillic tail into membrane of bacteria and causes loss of membrane potential

Is daptomycin bactericidal or bacteriostatic?

bactericidal

What type of bacteria is daptomycin effective against?

gram +

What is daptomycin used for?

skin + soft tissue infections

endocarditis

bacteremia

What is a major difference between protein synthesis in humans vs bacteria?

ribosomes/ribosomal subunits are different

What are examples of aminoglycosides?

Gentamicin

Tobramycin

Streptomycin

Neomycin

Whta is the MOA of aminoglycosides?

irreversibly block initiation of translation

What are aminoglycosides used to treat?

aerobic gram - bacilli infections

What type of drugs are Gentamicin, Tobramycin, Streptomycin

Neomycin

aminoglycosides

Are aminoglycosides bactericidal or bacteriostatic?

bactericidal at full concentration

What is a downside to aminoglycosides?

post-abs effect due to irreversibly binding

Why are aminoglycosides used topically??

very polar so have poor GI absorption

Why are aminoglycosides often given with B-lactams?

B-lactams affect the cell wall, allowing aminoglycosides to gain entry, increasing the effects

What are the side effects of aminoglycosides??

nephrotoxicity and ototoxicity

What is the MOA of tetracyclines?

inhibit bacterial protein synthesis (continuation)

What are examples of tetracyclines?

Tetracycline

Doxycycline

Minocycline

How is Tetracycline administered? What do you have to watch out for?

orally

absorption is hindered by foods with metal ions

What are the side effects of tetracycline?

discoloration of teeth

bone damage

disruption of flora if not fully absorbed

N/V/D

sensitivity to UV light

What is the MOA of macrolides?

present continuation of bacterial protein synthesis

What kind of bacteria are macrolides effective against?

gram +

What is the spectrum of tetracyclines?

broad spectrum

How are macrolides administered?

orally

What are macrolides used for?

community acquired respiratory infections