Antibiotics Introduction

Question 1

From where are antibiotics derived?

Answer 1

Produced by bacteria, fungi and also includes synthetically produced antimicrobial agents too

Question 2

What are the possible general mechanisms of how antibiotics destroy/slow growth of bacteria?

Answer 2

Inhibit cell wall synthesis
Inhibit protein synthesis
Inhibit nucleic acid replication and transcription
Damage plasma membrane
Inhibit essential metabolite synthesis

Question 3

What are some downside effects of using antibiotics?

Answer 3

All antibiotics can potentially be allergenic (from mild rash to anaphylaxis to Stevens-Johnson Syndrome)

Cross-sensitivity between different classes of agents

Attacks normal body flora (can result in opportunist infection i.e. candida and C. diff)

Question 4

Which antibiotics inhibit cell wall synthesis?

Answer 4

Beta-lactams
Vancomycin
Daptomycin
Bacitracin

Question 5

Which antibiotics directly destroy cell membrane?

Answer 5

Detergents i.e. Polymyxin

Question 6

Which antibiotics interfere with protein synthesis by interacting with bacterial ribosomes?

Answer 6

Chloramphenicol
Tetracyclines
Macrolides
Ketolides
Clindamycin
Streptogramins

Question 7

Which antibiotics block protein synthesis, specifically initiation (first step in synthesis)?

Answer 7

Oxazolidinones block protein synthesis

Within that class…
Linezolid blocks initiation

Question 8

What antibiotics inhibit tRNA synthesis?

subsequently interferes with protein synthesis

Answer 8

Mupirocin

Question 9

Which antibiotics lead to disruption of RNA processing through multiple mechanisms?
(subsequently interferes with protein synthesis)

Answer 9

Aminoglycosides

Question 10

Which antibiotics inhibit DNA processing and specifically what part of processing?

Answer 10

Quinolones (inhibit DNA topoisonerases, which regulate DNA under/overwinding)

Rifampin (DIRECT inhibition of DNA-dependent RNA polymerases)
Nitrofurantoin (INDIRECT inhibition of DNA-dependent RNA polymerase)

Question 11

Which antibiotics block bacterial folic acid pathway (interferes with metabolite production)?

Answer 11

Trimethoprim

Sulfonamides

Question 12

What are two ways antibiotics are used?

Answer 12

Empirical therapy using broad spectrum antibiotics

Definitive therapy using specific antibiotic selectively targeting the organism along with least potential for toxicity

Question 13

When might BACTERICIDAL agents be more useful in certain patients?

Answer 13

Patients with bacterial endocarditis, bacterial meningitis, neutropenia, or with acquired immunodeficiency syndrome

*Antibiotic may fail despite being appropriate, due to poor host defenses (humoral and/or cellular immunity issues)

Question 14

Other than poor host immunity, what other host factors must be accounted for when considering antibiotics?

Answer 14

Age (young and elderly have different renal and hepatic metabolism than adults)

Genetic factors i.e. G6P deficiency drug-induced acute hemolysis

Pregnancy

Drug allergies

Nervous system disorders i.e. high dose of PCN G triggering seizure, NMJ blocking effects of certain antibiotics in myasthenia gravis patients

Question 15

What is the difference between bactericidal versus bacteriostatic?

Answer 15

Bactericidial = directly KILLS bacteria
i.e. inhibit cell wall synthesis, disrupt plasma membrane… includes aminoglycosides and DNA gyrase inhibitors too

Bacteriostatic = arrests GROWTH/REPLICATION of bacteria BUT depends on host immunity to eliminate the pathogen
i.e. non-aminoglycoside inhibitors of protein synthesis like macrolides…also antifolate drugs

*there are exceptions, not black and white categorization

Question 16

How is antibiotic resistance defined?

Answer 16

Resistance happens if the concentration needed to inhibit/kill the microorganism is greater than the concentration that can safely be achieved

Antibiotic use can promote resistance by exerting selective pressure, resulting in bacteria acquired resistance to survive

Innate resistance of bacteria is a LONG-STANDING characteristic of a particular bacteria species

Question 17

What are the mechanisms of antibiotic-resistance?

Answer 17

Drug fails to reach target and intracellular concentration is insufficient
i.e. change in cell wall to increase efflux in TCN and quinolone resistance;
decreased cell membrane permeability in beta-lactam and quinolone resistance;
decrease cytoplasmic membrane transport in aminoglycoside resistance

Drug inactivation i.e. lactamases deactivating beta-lactams, phosphotransferases and acetyltransferases deactivating aminoglycosides

Altered target binding site i.e. DNA gyrase preventing quinolone binding, methylation of rRNA to prevent macrolide binding

Bypassing need for binding site i.e. bacteria using alternate metabolic route in folate synthesis so that trimethoprim no longer works

Question 18

Give an example where transduction results in antibiotic resistance

Answer 18

Transduction = transfer of genetic material via bacteriophage

i.e. Staph aureus and Erythromycin: plasmid codes for RNA methylase enzyme which changes a single adenosine in rRNA…meaning that erythromicin can no longer bind to the ribosomal subunit to inhibit protein synthesis

Question 19

Give an example of transformation resulting in antibiotic resistance

Answer 19

Transformation = DNA uptake from environment

i.e. DNA bits from closely related species of streptococcus gives resistance to pneumococci and Neisseria, resulting in resistance to PCN

Question 20

Give an example of conjugation resulting in antibiotic resistance

Answer 20

Conjugation = direct exchange of genes through bridge
Requires R-determinant plasmid encoded for resistance, RTF (resistance transfer factor) with genes needed for conjugation process = resistant R-factor (when the two independent plasmids join)

i.e. Conjugation primarily occurs among gram-negative bacilli

Question 21

Give 3 examples of MULTIPLE drug-resistant bacteria (danger)

Answer 21

MRSA (methicillin-resistant staphylcoccus aureus)

VRE (vancomycin resistant enterococcus)

Mycobacteria tuberculosis