Antimicrobial Resistance Flashcards
Sulphonamide Antibiotic
Bacteriostatic
Synthetic
Used for UTIs,RTIs,bactaraemia and prophylaxis for HIV+
Some host toxicity
Beta-lactams mechanism and examples
Interferes with the synthesis of peptidoglycan component of bacterial cell wall
Binds to penicillin-binding proteins
These catalyse a number of steps in peptidoglycan synthesis
Penicillin & methicillin
What is an antibiotic
An antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms
Reasons for increased mortality, morbidity and cost from AB res.
Increased time to effective therapy
Requirement for additional approaches (surgery)
Use of expensive therapy (newer drugs)
Use of more toxic drugs
Use of less effective ‘second choice’ antibiotics
Aminoglycosides mechanism and examples
Bactericidal-targets protein synthesis, RNA proofreading causing damage to cell membrane
Toxicity has limited use, but AB resistance has led to increase usage
Gentamicin,streptomycin
Rifmapicin mechanism
Bactericidal
Targets RpoB sunbunit of RNA polymerase
Frequent spontaneous resistance
Vancomycin mechanism
Bactericidal
Targets Lipid II components of cell wall biosynthesis, as well as wall cross linking via D-ala residues
Toxicity has limited use but other AB res. Has led to increase usage
Linezolid mechanism
Bacteriostatic
Inhibits initiation of protein synthesis by binding to 50S rRNA subunit
Gram+ spectrum of activity
Daptomycin mechanism
Bactericidal
Targets bacterial cell membrane
Gram+
Toxicity limits dose
4 AB res. Mechanisms
Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation
Altered target site
Acquisition of alternative gene or a gene that encodes a target modifying enzyme
Inactivation of antibiotic
Enzymatic degradation or alteration rendering antibiotic ineffective
Altered metabolism
Increased production of enzyme substrate can out-compete antibiotic inhibitor
Decreased drug accumulation
Reduced penetration of AB into bacterial cell and/or increased efflux of AB out of the cell - drug does not reach conc. required to be effective
Macrolides mechanism and examples
Gram+ and some gram-
Targets 50S ribosomal subunits preventing amino-acyl transfer and thus truncation of polypeptides
Quinolones
Synthetic, broad spectrum, Bactericidal
Target DNA gyrase in Gm -ve and topoisomerase IV in Gm+ve
Sources of antibiotic resistance
Plasmids- Extra chromosomal circular DNA
Transposons- Integrate into chromosomal DNA which allows transfer of genes from plasmid to chromosome and vice versa
Naked DNA - released by dead bacteria into environment
Spread of AB resistance genes
Transformation - uptake of extracellular DNA
Conjugation - pilus mediated DNA transfer
Transduction - phage (infection) mediated DNA transfer
Other reasons for treatment failure
Inappropriate choice of AB
Poor penetration of AB into target site
Inappropriate dose
Inappropriate administration (IV vs Oral)
Presence of AB resistance within commensal flora
Why are hospitals such strong selection pressures for AB resistance
Large numbers of infected people
High doses of AB
Risk factors for HAI
High number of ill people! (immunosuppression)
•Crowded wards
•Presence of pathogens
•Broken skin – surgical wound/IV catheter
•Indwelling devices - intubation
•AB therapy may suppress normal flora
•Transmission by staff – contact with multiple patients
Addressing resistance
Prescribing strategies – tighter controls, temporary withdrawal of certain classes. Restriction of ABs for certain serious infections
•Reduce use of broad-spectrum antibiotics
•Quicker identification of infections caused by resistant strains
•Combination therapy
•Knowledge of local strains/resistance patterns
Overcoming resistance
•Modification of existing medications to e.g. Prevent cleavage (beta-lactams) or enhance efficacy. E.g. Methicillin.
•Combinations of antibiotic + inhibitor of e.g. Beta-lactamase. E.g. Augmentin.
