Hospital Acquired Infection and Antibiotic Resistance Flashcards
First Sulphonamide Antibiotic
Prontosil - bacteriostatic, fully synthetic, treats UTI, RTI, Bacteraemia, prophylaxis (for HIV+ PEOPLE).
Beta-Lactam antibiotics:
interfere with synthesis of peptidoglycan part of bacterial cell wall. e.g. Penicillin and Methicillin. They bind to penicillin-binding proteins, which catalyse steps in the peptidoglycan synthesis.
Antibiotic what, made, mechanism?
antimicrobial agent produced by MO that kills/inhibits other MOs. Most are produced by soil-dwelling fungi or bacteria. They are selectively toxic - some target pathways that are present in human cells, but only the bacterial version. Others target bacterial specific pathways
Types of antibiotic:
- antimicrobial - chemical that kills/inhibits microbes
- Bactericidal - kills bacteria
- Bacteriostatic - stops bacteria growing
- Antiseptic - chemicals that kill/inhibit microbes that are usually used topically to prevent infection.
Aminoglycosides
gentamycin, streptomycin are bacteriocides.
Target protein synthesis (30S ribosomal subunit),
RNA proofreading and damage cell membrane.
They are toxic so have limited use.
Rifampicin + Vancmycin
bactericidal - targets RNA polymerase subunit, but spontaneous resistance = frequent. Compliance affected as it makes secretions red/orange.
Vancomycin - targets MRSA
Linezolid
bacteriostatic - inhibits initiation of protein syntehsis by binding to 50S rRNA subunit. Gram positive.
Daptomycin
bactericidal - targets cell membrane of gram positive, toxicity limits dose.
Macrolides
erythromycin + azithromycin - treat both gram-positive and gram negative infections. They prevent amino-acyl transfer and polypeptide formation.
Quinolones
fully synthetic, bactericidal, broad spectrum. Target DNA gyrase (bacterial supercoiling) in Gram-negative, and topoisomerase IV in gram positive.
What is the breakpoint?
the concentration of antibiotic required to inhibit growth (this needs to be clinically achievable).
Minimal Inhibitory Concentration?
lowest conc of AB to prevent bacterial growth
How does resistance occur?
Use of penicillin can provide selective pressure for the acquisition and maintenance of resistance genes.
Resistance usually emerges soon after the arrival of a new AB. except for erythromycin which took longer. Has occured for every antibiotic
How does resistance affect hospitals?
This resistance can lead to increased mortality, morbidity and cost → increase time for effective therapy, additional approaches required (surgery), use of expensive therapies (newer drugs), more toxic therapies (vancomycin -MRSA), and less effective (second choice antibiotics).
Antibiotic Resistance - Altered Target site?
Acquire spontaneous mutations that alter target seuqence e.g. MRA encodes alternative PBP (low affinity for beta-lactams). Streptococcus pneumoniae can become erythromycin resistance after acquiring erm gene (for enzyme that methylates AB target site)
Antibiotic resistance - inactivation of antibiotic?
Enzymatic degradation/alteration - ineffective antibiotic e.g. beta-lactamase and chloramphenicol acetyl-transferase. ESBL + NMDL-1 are beta-lactamases that can degrade a wide range of beta-lactams.
Antibiotic Resistance - Altered Metabolism?
Increased production of enzyme substrate that can out compete antibiotic inhibitor (increased production of PABA → resistance to sulfonamides). OR bacteria switch to other metabolic pathways, reducing requirement for PABA.
Antibiotic Resistance - Decreased drug accumulation?
reduced penetraiton of AB into bacterial cell/ increased efflux of AB out of cell. Drug doesnt reach concentration to be effective. This occurs especially in gram-negative bacteria which have 2 peptidoglycan cell wall.
Sources of antibiotic resistant genes?
Plasmids - extra-chromsomal circular DNA (often multiple copies), often carry multiple AB res genes
Transposons - Integrate into chromosomal DNA - allows transfer of genes from plasmids to chromosomes
Naked DNA - DNA from dead bacteria released to environment.
Non-genetic mechanisms of resistance/failure?
Biofilm - sticky large mass
Intracellular location - TB e.g. hides inside cells
Slow growth - TB grows slowly and is much harder to kill
Spores -
Persisters - dormant, not using machinery to make the cell or for growth, AB has no target to kill cell.
Inappropriate choice for organism
Poor penetration of AB into target site
Inappropriate dose and administration (oral vs IV)
Presence of AB resistance within commensal flora
Risk factors for hospital acquired infections?
High number of immunosuppressed (ill) people Crowded wards Presence of pathogesn Broken skin (IV, surgical wound) Indwelling devices Transmission by staff
How to address HAI resistance?
reduced use of broad spectrum antibiotics, quicker identification of infections, combination therapy, tighter controls, and withdrawal if needed on prescribing
How to overcome HAI resistsance?
modify exisiting medications i.e. prevent cleavage (beta-lactams) and enhance efficacy, combine antibiotic and inhibitor of beta-lactams.
