Hospital-acquired infection and antibiotic resistance Flashcards
Hospital acquired infections: list the reasons for the high rate of hospital acquired infection Antimicrobial mechanisms: summarise the mechanisms of action of important antimicrobials, and recognise that antimicrobial therapy provides a selection pressure for the spread of antimicrobial resistance Antimicrobial resistance: summarise the mechanisms of antimicrobial resistance, list important bacterial pathogens that are multi-drug resistant, and explain why antimicrobial resistance is associ
What is an antibiotic?
An antimicrobial PRODUCED BY A MICROORGANISM that kills or inhibits other microorganisms. Most produced by soil-dwelling fungi or bacteria. Some antibiotics today are semi-synthetic (modifies) and synthetic antimicrobials.
What do antimicrobials target?
TRICK QUESTION – kindaaa Bacteria, fungi OR virus.
Trend in antibiotic discoveries over the years?
Slowed dramatically.
What is the breakpoint (in terms of antibiotic concentration)? How are bacteria defined as antibiotic resistant?
Breakpoint – concentration of an antibiotic that we can reasonably expect to achieve in a target tissue. Bacteria that can replicate above the breakpoint is termed resistant.
What is MIC?
Minimal Inhibitory Concentration. The lowest concentration of antibiotic required to inhibit growth.
How does mechanism of antibiotic resistance reflect evolution by natural selection?
In any population, there is diversity. NO selection pressure = AB-resistant strains have no advantage so maintain low prevalence. SELECTION PRESSURE = AB-resistant strains outcompete non-resistant strains, so gain high prevalence. Antibiotic provides selection pressure!
What is the correlation between AB-resistance and mortality, morbidity, length of hospital stay and cost? Why are each of these the case? (x3 reasons)
Morbidity means ‘the condition of being diseased’.
All increases. Obviously.
REASONS:
- Increased time until effective therapy given: When someone has infection, they are initially given front-line antibiotic. 24-48hrs required to determine presence of antibiotic-resistance – in which time, the antibiotic resistant strains are left untreated and grow.
- Antibiotic resistance may require surgery.
- May require newer drugs: more expensive.
Mechanism of aminoglycoside antibiotics?
Targets protein synthesis and corrupt process = mis-generation of proteins and breaks down bacterial membrane.
Mechanism of Rifampicin antibiotic?
Prevents transcription genes and targets RNA polymerase.
Mechanism of Vancomycin?
Interferes with cell wall biosynthesis.
Mechanism of Linezolid?
Targets protein synthesis in Gram-positive bacteria.
Mechanism of Beta-lactams?
e.g. Penicillin. Interfere with synthesis of peptidoglycan component of CELL WALL.
How do antibiotics have selective toxicity?
Occurs because of bacterial and mammalian differences. Many bacterial metabolic processes are similar to human processes e.g. protein synthesis; but structures in bacteria different, meaning that antibiotic only has real-time effect on bacteria. Some processes are also totally different e.g. peptidoglycan synthesis. NB: antibiotics aren’t not toxic to humans, they’re just so much more toxic to bacteria than us.
What are the four mechanisms of antibiotic resistance?
It can alter target site of the antibiotic, inactivate antibiotic, change its own metabolic profile, or decrease accumulation of antibiotic.
How does altered target site mechanism of AB-resistance occur? (x3 mechanisms)
Acquire spontaneous mutation that change tertiary structure so that antibiotic cannot bind, but small enough to still maintain functionality. Alternative mechanisms: bacteria acquire way of modifying target (bacteria produces enzyme that alters target site so that it keeps on producing protein, but no longer recognised by antibiotic), or acquires a different target (that carries out same function but not recognised by antibiotic gene).
How does antibiotic inactivation mechanism of AB-R occur? (x2 mechanisms)
Enzymes secreted that degrade or modify antibiotic. Can also be enzyme-independent: bacteria release parts of itself that act as decoys and soak up antibiotic.
How does altered metabolism mechanism of AB-R occur? (x2 mechanisms)
Some antibiotics work by acting as enzyme inhibitors for the bacteria’s metabolic reactions. Some bacteria become resistant by increasing production of the enzyme substrate –> substrate out-competes the antibiotic enzyme inhibitor = so antibiotic does not work, metabolic processes continue as normal, and bacteria get the products needed to survive. Alternatively: bacteria switch to other pathway for metabolism.
How does decreased drug accumulation mechanism of AB-R occur?
Bacteria can reduce amount of AB that gets into itself. Gram-negatives have double phospholipid bi-layer. Outer-layer has LPS = hard barrier for antibiotic to cross. Bacteria also have selective ATP-dependent pumps – some pump out antibiotics to keep concentration low.
List three DNA sources of antibiotic resistant genes?
Plasmids – extra-chromosomal DNA can carry multiple AB-resistant genes. Transposons integrate into chromosomal DNA. Allows transfer of genes from plasmid to chromosome and vice versa. Naked DNA – from dead bacteria released into environment.
How can AB resistance genes be spread between bacteria? (x3)
Transformation – from environment Conjugation – pilus-mediated DNA transfer between two bacteria. Transduction – phage transfer.
Why has antibiotic resistance been around longer than antibiotics?
Antibiotics produced naturally by fungi and bacteria.
Why is there high rate of AB-resistance in hospitals?
Large numbers of people receiving high dose of antibiotics so huge selection pressure on AB-R organisms.
Reasons for high rate of hospital acquired infection? (x6)
High number of ill people = immunosuppression.
Crowded wards.
Presence of lots of pathogens.
Broken skin (surgical wound, catheter) = focal point for infection initiation.
People on ABs have suppressed gut flora, leaving door open to pathogens.
Commensal bacteria out-compete naturally-colonising-gut-pathogen in gut, but AB therapy gets rid of commensal bacteria which leaves pathogen able to replicate and present itself in high enough levels for symptomatic infection. This can spread to other patients.
Transmission by staff.
Ways to address emerging resistance? (x6 + x1).
Quicker identification of infections caused by resistant strains.
Combination therapy.
Prescribing strategies – tighter controls, temporary withdrawal of certain classes, stop overprescribing.
Reduce use of broad-spectrum antibiotics.
Correct dosage – low dose = larger AB-R chance.
Sticking to prescription.
Always Q**(uestion) **C**u**PB**oar**DS
AND, modifying existing drugs. This works.
