Antimicrobial Resistance & MDRO Flashcards
Caoimhe
Antibiotics may be bacteriostatic/bactericidal
What does a bacteriostatic antibiotic do?
The antibiotic prevents the growth of bacteria
Antibiotics may be bacteriostatic/bactericidal
What does a bactericidal antibiotic do?
The antibiotic kills bacteria
Various antimicrobial agents act by interfering with what? (4)
- Cell wall synthesis
- Plasma membrane integrity
- Nucleic acid synthesis
- Ribosomal function
Antibiotic Classes
What do B-Lactams do to kill bacteria? and an example?
Inhibit bacteria cell wall synthesis
Eg; Amoxicillin
AMR
When does AMR occur?
When microbes evolve mechanisms that protect them from the effects of antimicrobials
AMR
AMR consequences (4)
- Limited treatment for infections -> delayed treatment
- Increased risk of transmission
- Accumulation of antimicrobial resistance
- Panresistance -> microbe resistant to everything
AMR
(3) Stages of AMR evolution
- Genetic mutation as a result of selective pressures
- Horizontal gene transfer (HGT)
- Vertical gene transfer (clonal dissemination) and subsequent transmission of resistant strains from person -> person or from other sources (animals, environmental sources)
AMR
Main drivers of AMR (3)
- Overuse and misuse of antimicrobials
- Poor hygiene/ sanitation
- Substandard infection control measures in healthcare/agriculture
(3) Stages of horizontal gene transfer
- Transformation
- Translation
- Conjugation
What happens during the third stage of HGT?
Conjugation:
Cells need direct contact, with this a channel forms for DNA to pass
AMR
What are plasmids?
Small, extra-chromosomal DNA molecules that can replicate independently.
AMR
What were antibiotics used for in agriculture and what did this promote?
Antibiotics in low concentrations were used as growth promoters for animals in agriculture. This resulted in resistance among bacteria
AMR
MDRO definition
Microorganisms resistant to three or more classes of antimicrobial drugs
AMR
Beta lactam antibiotics examples? (2)
- Penicillins
- Carbapenems
AMR
Clinically significant resistance -> Gram positive organisms examples? (4)
Staphylococcus species:
1. Staphylococcus aureus
2. Coagulase negative Staphylococci (CNS)
Enterococcus species:
3. E. faecium
4. E. faecalis
AMR
CNS are examples of opportunistic bacteria. Define opportunistic bacteria?
Microorganisms that don’t usually cause disease, however can become pathogenic under certain conditions -> weakened immune system - immunocompromised
Staph aureus infection associated with?
- Skin (abscesses, cellulitis)
- UTI
- BSI (blood stream infection)
- Osteomyelitis
- Foodpoisoning
Staph aureus infection treatment (2)
- Cephalexin (beta lactam) for uncomlicated skin infection
- Vancomycin (glycopeptide antibiotic) for comlicated/invasive infections -> bacteraemia, pneumonia, etc.
MRSA definiton
Any strain of S. aureus that has developed (through natural selection) or acquired (throughHGT) mutiple drug resistace to several beta-lactam antibiotics, most notably methicillin
Explain how MRSA works !
- Methicillin and beta-lactams bind to and inhibit penicillin binding protein (PBP)
- PBP is an enzyme that assists with peptidoglycan assembly.
- When PBP is inhibited the peptidoglycan matrix cannot properly be formed and the bacterial cell will burst
- An alternative penicillin binding protein is coded for, preventing methicillin binding
- Confers resistance to multiple beta-lactam antibiotics (penicillin based)
Enterococcus Species
Infections caused by Enterococci species? (4)
- UTIs
- Bacteraemia
- Endocarditis (inflammation of the endocardium)
- Meningitis
Enterococcus Species
Enterococcus species infection treatment? (2)
- Nitrofurantoin (nitrofuran class) for uncomplicated UTI
- Vancomycin (glycopeptide class) for invasive infections
VRE
VRE description
- Nosocomial pathogens that are persistant in hospital environment
- Resistance to several antibiotics limits treatment options
- VRE infection liked with extended hospital stays
How does vancomycin work?
- Binds to the D-Ala-D-Ala terminus of peptidoglycan precursor, inhibiting transglycosylation and transpeptidation, and causing cell wall damage
How is resistance to vancomycin conferred?
By the acquisition of the vanA or vanB gene that alter the D-Ala-D-Ala target of vancomysin
Treatment for vancomycin resistant strains
- Linezolid and daptomycin
- Final resort antibiotics
VRSA (Vancomycin Resistant S. Aureus)
What is VRSA mediated by?
A vanA gene cluster which is transferred from vancomycin resistant enterococci via transposon
Clinically significant resistance-> gram negative microorganisms (2)
Primarily Enterobacterales
1. Extended spectrum beta-lactamase producers (ESBL)
2. Carbapenemase producing enterobacterales (CPE)
How do ESBLs work?
They are associated with enzymes (beta-lactamases) that hydrolyse the beta-lactam ring of penicillins and cephalosporins
Solution to ESBLs? (2)
- Supplement antibiotics with a beta-lactamase inhibitor eg: augmentin
- Use carbapenems
CPEs
What are CPEs resistant to?
All antibiotics derived from penicillins
What are Carbapenems?
Drugs of last resort, with broad spectrum of activity against gram negs and some gram pos.
Antimicrobial control measures (4)
- Screening before entering intensive wards (for MRSA, VRE, CPE)
- Surveillance reporting
- Patient isolation
- Hygiene measures
How is MRSA screened for
Swabs from nose, axilla, groin are plated on selective and differental media in hospital lab
VRE screening
Culture from rectal swabs plated on selective and differential media in hospital lab
CPE (and ESBL) screening
Culture from rectal swabs. Molecular approach available for urgent swabs.
How could bacteriophages be used as an AMR solution?
Regulation of ecosystem: maintenance of population levels by predation
Bacteriophage and viral infection of bacteria: how does it work?
- Bacteriophage attaches itself to bacterium and infects host cell
- It hijacks the bacteriums cellular machinary to produce viral components
- New bacteriophages assmeble and burst out of bacterium -> called lysis
