Antibiotics Introduction Flashcards
From where are antibiotics derived?
Produced by bacteria, fungi and also includes synthetically produced antimicrobial agents too
What are the possible general mechanisms of how antibiotics destroy/slow growth of bacteria?
Inhibit cell wall synthesis Inhibit protein synthesis Inhibit nucleic acid replication and transcription Damage plasma membrane Inhibit essential metabolite synthesis
What are some downside effects of using antibiotics?
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)
Which antibiotics inhibit cell wall synthesis?
Beta-lactams
Vancomycin
Daptomycin
Bacitracin
Which antibiotics directly destroy cell membrane?
Detergents i.e. Polymyxin
Which antibiotics interfere with protein synthesis by interacting with bacterial ribosomes?
Chloramphenicol Tetracyclines Macrolides Ketolides Clindamycin Streptogramins
Which antibiotics block protein synthesis, specifically initiation (first step in synthesis)?
Oxazolidinones block protein synthesis
Within that class…
Linezolid blocks initiation
What antibiotics inhibit tRNA synthesis?
subsequently interferes with protein synthesis
Mupirocin
Which antibiotics lead to disruption of RNA processing through multiple mechanisms?
(subsequently interferes with protein synthesis)
Aminoglycosides
Which antibiotics inhibit DNA processing and specifically what part of processing?
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)
Which antibiotics block bacterial folic acid pathway (interferes with metabolite production)?
Trimethoprim
Sulfonamides
What are two ways antibiotics are used?
Empirical therapy using broad spectrum antibiotics
Definitive therapy using specific antibiotic selectively targeting the organism along with least potential for toxicity
When might BACTERICIDAL agents be more useful in certain patients?
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)
Other than poor host immunity, what other host factors must be accounted for when considering antibiotics?
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
What is the difference between bactericidal versus bacteriostatic?
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
How is antibiotic resistance defined?
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
What are the mechanisms of antibiotic-resistance?
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
Give an example where transduction results in antibiotic resistance
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
Give an example of transformation resulting in antibiotic resistance
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
Give an example of conjugation resulting in antibiotic resistance
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
Give 3 examples of MULTIPLE drug-resistant bacteria (danger)
MRSA (methicillin-resistant staphylcoccus aureus)
VRE (vancomycin resistant enterococcus)
Mycobacteria tuberculosis
