Antimicrobial resistance Flashcards
General MoA of B lactams
they mimic D alanine, interaction with penicillin binding proteins (PBP) blocks cross linking and compromises cell wall rigidity. Cell weakened and more prone to external stress. Will eventually lead to lysis in an actively growing cells as a result of no crosslinking
ESBLs are resistant to which antibiotics?
Cephalosporins and Penicillins and able to degrade Aztreonam
ESBLs are inhibited by what?
clavulanic acid
What are ESBLs produced by?
E. coli and Klebsiella species
Which B lactam subclass is not hydrolysed by ESBLs?
carbapenams so used to treat severe HC associated infections
What is an infection with ESBL producing bacteria associated with?
increased time to effective therapy, increased length of stay, increased mortality & overall healthcare costs
What are the treatment options for ESBL infections?
beta lactam + b lactamase inhibitor (co-amoxiclav) or Carbapenems
What are CPEs?
a group of bacteria capable of hydrolyzing almost all beta lactams, they are encoded on plasmids and highly transmissible
CPE infection is very difficult to treat and causes similar problems to ESBLs, what can be done about this?
effective infection control, development of new antibiotics, development of new lactamase inhibitors, repurposing old antibiotics
What is the difference between bacteriostatic and bactericidal?
bacteriostatic (e.g. protein synthesis inhibitors such as tetracycline which bind reversibly to ribosome and inhibit growth) & bactericidal (cell killing such as b lactams)
What are the 4 main target classes of antimicrobials?
cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways
What are some reasons for resistance to antibiotics?
natural resistance such as lack of target structure or impermeable to antibiotic / sensitive bacteria develop resistance (acquired) via enzymatic inactivation of antibiotic, modification of target, efflux mechanisms
What is antibiotic resistance and why does it develop?
it’s the acquired ability of a microorganism to become desensitised to the effects of a chemotherapeutic agent. Can develop because of a selection pressure of the antibiotic, transfer of resistance genes or rapid cell division
Give some biochemical mechanisms of antibiotic resistance
overproduction/ alteration of target, alternative pathway, decreased influx/increased reflux, drug modification & drug destruction
How do microorganisms acquire ability to resist antibiotics?
horizontal gene transfer, transfer of genetic material between cells, even of different species, independent of cell replication via transformation, transduction, and conjugation
Resistance plasmids have transfer operon, what does that allow it to do?
enables it to spread from one organism to another, encodes for conjugation
What do biofilms do?
make organism less susceptible to antimicrobials
How can we respond to AMR?
antimicrobial stewardship (start smart then focus), combination therapy & developing new drugs
What does it mean if a patient is colonised with MRSA?
They carry it but it is causing no problems or symptoms - they are however at risk of developing an infection with MRSA
What are the signs and symptoms of an MRSA infection?
High temp,
Fever
High white cell count
Inflammation at the infection site
What are the 1st and 2nd line treatments for a serious MRSA infection?
IV Vancomycin &Teicoplanin, second line agents include linezolid, daptomycin and tigecycline
What are coliforms?
Gram negative bacilli resident in the gut e.g. e.coli
How is C.diff treated?
Oral Metronidazole
Oral Vancomycin
How can MRSA infections be reduced in hospitals?
Screen at risk patients/ Isolate patients/ Decontamination therapy to the risk of infection/spread of others/ Handwashing/ Aseptic non-touching techniques/ Antibiotic prophylaxis against MRSA for surgery in colonised patients
Which antibiotics is MRSA resistant to?
All B lactams including Penicillins, cephalosporins and carbapenems. Many strains also resistant to others eg macrolides, quinolones & clindamycin
Which parts of the body can be colonized with S.aureus?
skin, nose, armpits, axilla (armpits) and perineum (groin)
High level resistance to methicillin is caused by what?
the mecA gene, which encodes an alternative penicillin binding protein, PBP 2a
Why do GRE infections occur?
glycopeptide antibiotics are used to treat MRSA infections, some patients with frequent antibiotic exposure can become colonized in bowel with GRE, infections are often IV line associated and have limited treatment options
Describe the VRE mechanism and vancomycin susceptible enterococci mechanism
VSE make cell wall precursors that have high affinity for vancomycin, they bind to vancomycin and inhibit cell wall synthesis however with VRE the presence of vancomycin makes cell wall precursors that have low affinity for vancomycin so do not bind and cell wall synthesis is not inhibited
What does antibiotic stewardship entail?
ensuring antibiotics are used rationally and not misused, health promotion, prescriber education, development/promotion of empiric guideline choice, restriction of reserve antibiotics, review/advise on management of infection for individual patients
How can antibiotics be misused?
prescribed unnecessarily, administration delayed in critically ill patients, broad spectrum used too generously, narrow spectrum used incorrectly, dose is lower or higher than appropriate for patient, wrong duration, treatment not streamlined according to culture data results
What important steps should be taken when someone is suspected of having C.diff?
– assess severity (including WCC, abdominal pain and temp, stop antibiotic precipitating condition, avoid anti-diarrhoeal agents, stop gastric acid suppressive agents, stop laxatives, assess fluid balance and ensure hydration, assess nutritional status, initiate treatment
What steps can be taken to prevent C.diff infection?
careful use of antibiotics (minimise exposure to high risk agents like fluoroquinolones, cephalosporins, clindamycin / avoid prolonged courses / avoid exposure to multiple antibiotics), infection control, rigorous hand washing to prevent spread and re-infection
