Antimicrobial Therapy Flashcards
What was the first example of a sulphonamide antibiotic?
Prontosil
Bacteriostatic.
Synthetic
Examples include sulpha-methoxazole. Sometimes used together with Trimethoprim (co-trimoxazole).
Used to treat UTIs, RTIs, bacteraemia and prophylaxis for HIV+ individuals.
Becoming more common due to resistance to other antimicrobials, despite some host toxicity.
What is an antibiotic?
An antibiotic is an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms.
Made by soil fungi or bacteria.
Can be synthethic
What is a antimicrobial?
Antimicrobial – chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses).
What is an antiseptic?
Antiseptic – chemical that kills or inhibits microbes that is usually used topically to prevent infection.
What antibiotics were found in in the 1940s?
gramicidin Pencillin B Neomycin Streptomycin Cephalosporin
What antibiotics were found in the 1950s?
Chloramphenicol Chlortetracycline Polymyxin Erythromycin Vancomycin Cirginamycin
Examples of Aminoglycosides? What do they do?
E.g. Gentamicin, streptomycin.
Bactericidal.
Target protein synthesis (30S ribosomal subunit), RNA proofreading and cause damage to cell membrane.
Toxicity has limited use, but resistance to other antibiotics has led to increasing use.
Rifampcin?
Bactericidal.
Targets RpoB subunit of RNA polymerase.
Spontaneous resistance is frequent.
Makes secretions go orange/red – affects compliance.
Vancomycin?
Bactericidal.
Targets Lipid II component of cell wall biosynthesis, as well as wall crosslinking via D-ala residues
Toxicity has limited use, but resistance to other antibiotics has led to increasing use e.g. against MRSA
Linezolid?
Bacteriostatic.
Inhibits the initiation of protein synthesis by binding to the 50S rRNA subunit.
Gram-positive spectrum of activity.
Daptomycin?
Bactericidal.
Targets bacterial cell membrane.
Gram-positive spectrum of activity.
Toxicity limits dose.
What are Beta-lactams?
Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall.
Examples include Penicillin and methicillin.
Bind to penicillin-binding proteins.
PBPs catalyse a number of steps in the synthesis of peptidoglycan.
What are Macrolides?
E.g. Erythromycin, azithromycin.
Gram-positive and some Gram-negative infections.
Targets 50S ribosomal subunit preventing amino-acyl transfer and thus truncation of polypeptides.
What are Quinolones?
Synthetic, broad spectrum, bactericidal.
Target DNA gyrase in Gm-ve and topoisomerase IV in Gm+ve.
Antibiotic resistance occurs via which 4 distinct mechanisms?
Altered target site.
Inactivation of antibiotic.
Altered metabolism.
Decreased drug accumulation.
Examples of bacterial altered target site?
acquisition of alternative gene or a gene that encodes a target-modifying enzyme.
Methicillin-resistant Staphylococcus aureus (MRSA) encodes an alternative PBP (PBP2a) with low affinity for beta-lactams.
Streptococcus pneumoniae resistance to erythromycin occurs via the acquisition of the erm gene, which encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit.
Examples of bacterial inactivation of antibiotic?
Enzymatic degradation or alteration, rendering antibiotic ineffective.
Examples include beta-lactamase (bla) and chloramphenicol acetyl-transferase (cat).
ESBL and NDM-1 are examples of broad-spectrum beta-lactamases (can degrade a wide range of beta-lactams, including newest).
Examples of bacterial altered metabolism?
Increased production of enzyme substrate can out-compete antibiotic inhibitor (e.g. increased production of PABA confers resistance to sulfonamides).
Alternatively, bacteria switch to other metabolic pathways, reducing requirement for PABA.
Bacterial decreased drug accumulation examples?
Reduced penetration of AB into bacterial cell (permeability) and/or increased efflux of AB out of the cell – drug does not reach concentration required to be effective.
Penicillin Penicillin tetracycline Quinolone Cefotaxime Spectinomycin
Resistance mechanisms? What have they acquired due to them?
Penicillin : Penicillinases – plasmid transformation
Penicillin : Target site modification – point mutation
tetracycline : Efflux pump – Plasmid-conjugation
Quinolone : target site modification – Plasmid mutation
Cefotaxime : target site modification – Plasmid mutation
Spectinomycin : target site modification – Plasmid mutation
What does Pseudomonas aeruginosa do?
Gram -
Cystic fibrosis, burn wound infections. Survives on abiotic surfaces.
What does E.Coli do?
Gram -
GI infect., neonatal meningitis, septicaemia, UTI.
What does salmonella do?
Gram -
GI infect. , typhoid fever.
What does Acinetobacter baumannii do?
Gram -
Opportunistic, wounds, UTI, pneumonia (VAP). Survives on abiotic surfaces.
