Hospital acquired infection and antibiotic resistance Flashcards
What is Prontosil?
First example of an effective and safe anti-bacterial therapeutic
What are the main features of Prontosil?
Bacteriostatic
Synthetic
Used to treat UTI’s, RTI’s, bacteraemia and prophylaxis for HIV+ individuals
Sometimes used together with Trimethoprim- work better together
Becoming more common due to resistance to other anti-bacterials
What was the issues with Prontosil?
Only effective with Gram-positive bacteria (single outer membrane)
Why is it difficult to develop drugs against Gram-negative bacteria?
To get a drug across the outer layer it must be hydrophilic
And hydrophobic for the inner layer
What was the issue with early penicillin?
Excreted from the body very rapidly WH
What is a Beta-lactam?
Most commonly prescribed type of antibiotic
E.g pencilling and methicillin
Has a characteristic Beta-lactam ring
Chemically mimic components of peptidoglycan cell wall
Competitive inhibitor of enzymes involved in cell wall synthesis
What is an antibiotic? (strictly speaking)
Agent produces by microorganism the kills or inhibits another microorganism
However many are semi-synthetic or synthetic
What are the 4 types of antibiotic?
Antimicrobial
Bactericidal
Bacteriostatic
Antiseptic
Why did antibiotic discoveries slow down?
Economic factors
Already so many, why spend money acquiring more?
What did Flemming predict?
Resistance primarily due to misuse
What are the main features of resistance?
Constantly changing landscape- problems we face today are not what we will face tomorrow
Countries that use the most antibiotics have the most resistance
Resistance usually emerges soon after the new arrival of the new AB
Why is the market for antibiotics different from any other type of drug?
Newest drugs are kept sparingly for the most severe of cases- small market
Older drugs are in more demand
How does resistance come about?
Evolution by natural selection
Routine use of antibiotics provides selection pressure
What were the misconception at the dawn of the antibiotic era?
Resistance against more than one class of antibiotics would not occur at the same time
Horizontal gene transfer would not occur
Resistance organisms would be significantly less ‘fit’
What are the consequences of resistance?
Increased mortality, morbidity and cost
Increased time for effective therapy, requirement for additional approaches
Use of expensive therapy
More toxic drugs
Name some gram-negative resistant bacteria
Pseudomonas aeruginosa
E. coli
Salmonella
Acinetobacter
Name some gram-positive resistant bacteria
Staphylococcus aureus
Streptococcus pneumonias
Clostridium difficle
Myobacterium tuberculosis
What are Aminoglycosides?
E.g. Gentamicin, streptomycin Bactericidal Targets proteins synthesis, RNA proofreading and causes damage to cell membrane Toxic- limited use Increasing due to resistance to others
What is Rifampicin?
Bactericidal
Targets RpoB subunit of RNA polymerase
Spontaneous resistance frequent
Makes secretions go red
What is Vancomycin?
Bactericidal
Targets lipid II components of cell wall biosynthesis
Toxic
Increasing use due to resistance to others
What is Linezolid?
Bacteriostatic
Inhibits the imitation of protein synthesis
Gram-positive
What is Daptmycin?
Bactericidla
Targets cell membrane
Gram positive
Toxicity limits dose
What principle do antibiotic works on?
Selective toxicity
What are the 4 mechanisms of antibiotic resistance?
Altered target site
Inactivation of antibiotic
Altered metabolism
Decreased drug accumulation
How does the altered target site mechanism work?
Gene encodes a target-modifying enzyme
e.g MRSA encodes alternative enzyme with low affinity for Beta-lactams
Streptococcus pneumoniae encodes enzyme that methylates the AB target site
How does the inactivation of antibiotic mechanism work?
Enzymatic degradation or altering rendering antibiotic ineffective
How does the altered metabolism mechanism work?
Increased production of enzyme substrate can out-compete antibiotic inhibitor
Bacteria south to other metabolic pathways
How does the decreased drug accumulation mechanism work?
Reduced penetration of AB into bacterial cell
Increased efflux of AB out of cell
Drug does not reach concentration to be effective
What macrocolides?
E.g. erythromycin, azithromycin
Gram-positive and some gram-negative
Targets ribosomal sub-unit preventing amino-acyl transfer
What are quinolones?
Synthetic, broad spectrum, bactericidal
Target DNA gyrase in GM-ve
Toposomerase on GM+ve
What are the sources of antibiotic resistance genes?
Plasmids
Transposons
Naked DNA
What are transposons?
They integrate into chromosomal DNA allowing transfer of genes from plasmin to chromosome and vice versa
What are the non-genetic mechanisms of resistance?
Biofilm Intracellular location Slow growth Spores Persisters
What are other reasons for failure of antibiotics?
Wrong for organism
Poor penetration to target site
Wrong dose
Wrong administration
Why do hospitals provide strong elective pressure for AB resistance?
Large number so infected people receiving high doses of antibiotics
Strong selective pressure
What are some risk factors for HAI?
High no. of immunosuppressed Crowded wards Presence of pathogens Broken skin AB therapy may suppress normal flora Transmission by staff with contact with multiple patients
What can be done to address resistance?
Prescribing strategies Reduce broad-spectrum use Quicker identification Combination therapy Knowledge of strains and resistance patterns
