mportant antimicrobial resistant organisms Flashcards
how do bacteria become resistant to anitmicrobials:
1. Change the locks, so the key
(antimicrobial) no longer
works: — modification
2. Attack the antimicrobial with
enzymes that damage it: —
3. Brick up the doorway so the
antimicrobial can’t gain
access: – loss
4. Kick the antimicrobial out if it
manages to get in: —
target site
beta lactamase
porin
efflux
why have antimicrobial resistant bacteria emerged:
* Bacteria are survivors!
– Bacteria can be – resistant to certain antimicrobials
– Bacteria can acquire resistance to other antimicrobials to which they would usually be considered susceptible
* Bacteria are very good at — to develop resistance through – or — processes (conjugation, transformation, transposition, transduction)
* Suboptimal antimicrobial stewardship
– Non-compliance
* Prescriber not following guidelines
* Patient not completing prescribed course
– Lack of prescriber knowledge (e.g., about drug spectrum)
– Limited access to diagnostic facilities
– Inappropriate use in other sectors (e.g., agriculture) – need
‘One Health’ approach
inherently
adapting
mutation or genetic exchange
consequences of antimicrobial resistance AMR:
* Changes in microbial – : bacteria less –
* We get it wrong: – treatment fails while we’re waiting to find out the causative pathogen
– – appropriate treatment of sepsis
– Increased — /—of illness
– Increased –
– Increased healthcare –
* – hospital stays
* use of more— medications
* We’re afraid of getting it wrong, so we use — spectrum antimicrobials (selection of even more resistant bacteria)
* Even the broader spectrum antimicrobials can’t be relied upon to
work:
– common infections once easily treated with antimicrobials are now more difficult to treat (less choices)
fitness
susceptible
empiric
delayed
morbidity and duration
mortality
cost
longer
expensive
broader
multi resistant bateira w few available treatment options:
* Gram- –
– Some enterobacterlase (K. pneumoniae, E. cloacae, E. coli)
– Acinetobacter baumannii
– Pseudomonas aeruginosa
– Stenotrophomonas maltophilia
* Gram- —
– Meticillin-resistant Staphylococcus aureus (MRSA)
– Vancomycin-resistant enterococci (VRE)
* Others
– Multi-drug-resistant —
– Rapidly-growing —
– Mycobacterium – complex
-ve
+ve
Mycobacterium tuberculosis
mycobacteria
avium
key bacteria that can become resistant to antimicrobials:
1 —
2- —
3- —
4— as —- ,- —
- Penicillin-resistant Streptococcus
pneumoniae (pneumococci) - Meticillin resistant Staphylococcus aureus
(MRSA) - Vancomycin resistant enterococci (VRE)
- Resistant Enterobacterales:
– Extended spectrum β-lactamase (ESBL) producers
– Carbapenemase producers (CPE/CRE)
penicillin resistant streptococcus pneumoniae:
Also called Penicillin — or penicillin — S.pneumoniae (PNSP) in epidemiological reports
* How? Modification of the penicillin-binding proteins involved in cell- wall synthesis = —- modification
* Mainly associated with —- , —
*— -resistance to other antimicrobial classes is common
– Arises from acquisition of a gene – or – encoding resistance to multiple antimicrobials
– To date, resistance to — has not been reported
* — different serotypes associated with the pneumococcal capsule
which is the target for the available vaccines:
– 23-valent pneumococcal polysaccharide vaccine (PPV-23)
– 13-valent pneumococcal conjugate vaccine (PCV-13)
non wild type non susceptible
target site
community-acquired pneumonia (CAP) and bloodstream infection (BSI)
cross
cassette or transposon
vancomycin
90
methicillin resistant staphlycoccus aureus MRSA:
* Mainly associated with — and other – e.g. Long-term care facilities
* MRSA produces an —
(mec gene) = — modification
* Causes a similar spectrum of infections as meticillin susceptible S. aureus (MSSA)
* Associated with — associated infections:
– — infections
–— -related infections involving biofilms (e.g. peripheral and
central lines, prosthetic joint infections)
– —-
– –
– –
( MRSA is decreasing across the EU/EEA, but in many countries in
Southern Europe still have high levels)
hospital and healthcare environment
altered penicillin binding protein 2a
target site
healthcare associated
surgical site ( wound)
device
bloodstream infection
endocarditis
osteomyelitis
MRSA - meticillin resistant s.aureus:
* Results from production of an altered —
– Encoded by — gene
– Confers resistance to most — antibiotics including —
– mecA gene carried on a mobile genetic element known as —-
* A number of treatment options remain
– — or — (aka — )
– Or alternatives ( — , – , – )
* Limited reports of S. aureus resistant to —, such as vancomycin (Japan, USA 2002) – VRSA
Penicillin → Flucloxacillin → MRSA (treat with glycopeptides) → VRSA (vancomycin resistant)
altered penicillin binding protein PBP2a
mecA
flucloxacillin
staphylococcal cassette chromosome (SCCmec)
vancomycin or teicoplanin aka glycoprotein
daptomycin liezolid tetracyclins
glycopeptide
treatment of MRSA:
* Treatment should be prescribed on advice of an — specialist (microbiologist/ID physician)
– Restricted agents, costly, interactions with other medications, used for infections at specific body sites
* Important to remember:
– vancomycin : requires therapeutic drug monitoring (TDM) due to – and –
– Linezolid: can lead to —
* Not recommended for more than – weeks
* Infection prevention: Emergence and transmission of MRSA in healthcare settings is best prevented by:
– Standard precautions (including – )
– Antimicrobial –
– – of colonised patients with contact precautions
– Topical – of colonised individuals
infection
renal n ototoxity
bone marrow suppression
4
hand hygiene
stewardship
isolation
decolonisation
more info on linezolid:
The following additional points should be monitored and explained to the
patient:
1. Weekly — :
- —- (including anaemia, leucopenia, pancytopenia and thrombocytopenia)
2. Potential interactions with the – and tricyclic group of —
-Unless close observation and blood pressure monitoring is possible, linezolid is — for patients taking these drugs.
3. — neuropathy and — neuropathy reported
- Patients should be advised to report symptoms of visual impairment or any numbness or tingling felt in the extremities, or worsening of pre-existing neuropathy
4. Linezolid can increase the patient’s — when taken with food/beverages that contain high tyramine content
Example: cheese, beer and yeast or soya bean products , Patients should be advised to avoid these.
5. –
full blood counts
mylosuppression
SSRI ( serotonin reuptake inhibitors) , antidepressant
contradictiated
peripheral n optic
blood pressure
metabolic acidosis
check slide 23
vancomycin resistant enterococci VRE:
* Enterococci often found in the — tract (—-) or —
* Already inherently resistant to several antimicrobial classes:
– — , — , —
– E. faecium is mostly resistant to –
* VRE mostly encountered in – setting
– Not always associated with – (colonisation)
– Can cause—-
* Vancomycin targets the — in the
enterococcus cell wall
– Enterococci alter the amino acid side chains of the peptidoglycan cell wall = — modification
– So vancomycin can no longer bind and work = VRE
enteric ( bowel ) or perineum
cephalosporin , fluroquinlones , macrolids
amoxicillin
healthcare
infection
urinary tract infection (UTI), BSI, intra-abdominal infections
peptidoglycan
target site
VRE
* Resistance can develop through several different mechanisms:
– Some are located on the enterococcal –
– The vanA mechanism is located on a – which can be transferred between enterococci
– Some mechanisms confer resistance to vancomycin only (— ),
while others to both vancomycin and teicoplanin (—)
* Patients may become colonised with VRE (‘—-’)
* VRE carriers do not require — and enterococci whether vancomycin susceptible or VRE don’t cause—
– However, if have diarrhoea for another reason can shed VRE into
their environment – patient zone, shared toilet facilities
* Treatment of VRE infections should be based on — of the individual isolate
c/some
plasmid
vanB
vanA
carriers
treatment
diarrhoea
suscpeibitlities
AMR in enterobacterales:
* Enterobacterales = Large order of different Gram- — , —, facultatively — , —- that live in the – tract ( – )
– Escherichia coli, Klebsiella pneumoniae, Enterobacter
cloacae, Proteus mirabilis
* Can become resistant to the different antimicrobial classes used to treat infections they cause
– e.g., UTI, surgical site infections, BSI, intra-abdominal infections
– — , —- , —
Multi-drug resistance (MDR) = resistance to — – classes of antimicrobials
(e.g., Beta lactams, fluoroquinolones, aminoglycosides)
AMR IN ENTEROBACTERALES:
* —- are one of the most important classes used to treat infection caused by Enterobacterales:
– Penicillins– —
– —- – cefuroxime (2nd generation), ceftriaxone,
cefotaxime, ceftazidime (3rd generation)
– — – aztreonam
– — – meropenem, ertapenem
* Beta lactams act to inhibit — synthesis of members of the order Enterobacterales
* Acquisition of an enzyme (beta-lactamase) by Enterobacterales inactivates the — , so it no
longer works
-ve
non spore
anaerobic
rod bacilli
enteric aka bowel
b lactams ahminoglycosides and fluroonquinloes
more than 3 different
beta lactams
amoxilin
cephalosporin
monobactams
carpanems
cell wall
b lactams
1- important beta lactamases produced by enterobacterales:
* — – can inhibit beta lactam antibiotics with extended spectrum of
activity
– e.g. – generation cephalosporins, aztreonam
* —- – have the ability to destroy the last resort beta lactams with the largest spectrum of activity
(e.g. carbapenems). Also known as carbapenemase producing Enterobacterales (CPE) or carbapenem
resistant Enterobacterales (CRE):
– OXA-48, KPC, NDM, VIM, IMI carbapenemases
2- sharing genes:
Members of the order Enterobacterales can share the instructions for producing ESBLs and carbapenemases, using
—
– ESBL E. coli can share with
K. pneumoniae, so it
becomes ESBL K.
pneumoniae
– CPE E. cloacae can share
with E. coli, so it becomes
CPE E. coli
Extended spectrum beta lactamase (ESBL)
3rd
carpanemease
mobile genetic elements
(plasmids)
info:
- ESBL accounted for
12.6% of isolates
- Multi-drug
resistance (MDR)
accounted for 5.6 %
of isolates
how to treat infection causes by ESBL producing enterboctalase:
*—:
– Typically, — (meropenem) remain susceptible
– Reserved for – infection and – ill patients on advice from clinical microbiology/ID
* — – gentamicin, amikacin
* — – ciprofloxacin
* — – useful for uncomplicated UTI
(e.g. cystitis), as usually active against ESBL producers
beta lactams
carbapenems
sever n critically ill
aminoglycosides
flurioquilons
nitrofurantoin
the last resorts - carbapemes:
* Resistant to — by most — and
chromosomal —
* Have a very – spectrum of activity:
– Gram — (including ESBL-producing
Enterobacterales, Pseudomonas aeruginosa,
Acinetobacter baumanii)
– — (Bacteroides fragilis)
– Gram — i (Listeria spp.)
* Treatment of an infection caused by an ESBL with a carbapenem is associated with a more favourable outcome and clearance of infection
– — indicated for intra-abdominal infections,
meningitis and UTI
inactivation by plasmid n c/somal beta lactamase
broad
gram -ve bacili
aerobes
gram +ve
meropenems
how to treat infection caused by carbapenamase-prodcuing enterobacterlaes CPE:
WITH DIFFICULTY!
* Beta lactams – Typically carbapenems (meropenem) no
longer effective
* Newer beta-lactam/beta-lactamase inhibitor
combinations:
– Ceftazidime-avibactam
* Aminoglycosides – gentamicin, amikacin
* Fluoroquinolones – ciprofloxacin
* Tigecycline
* Colistin
* Nitrofurantoin – useful for uncomplicated UTI (e.g.
cystitis), as usually active against CPE
the last resorts : colisitin
* — (E) antimicrobial with many side effects:
– –
– –
* — – spectrum of activity (Gram-negative infections)
* –
– Binds to — and phospholipids in the outer cell membrane with disruption
* IV, IM or nebulised route
* Reserved for treatment of infection due to —
– e.g., CPE, MDR-Pseudomonas in cystic fibrosis, MDR-
Acinetobacter under specialist advice
* Resistance has emerged
polymyxin
side effects: – Nephrotoxic
– Neurotoxic
narrow
-ve
bactericidal
liposacrhides
MDR-GNB
other important organisms:
BACTERIA
* MDR-Pseudomonas
aeruginosa
* MDR-Acinetobacter
baumanii
* MDR- Neisseria
gonorrhoeae
* Ciprofloxacin resistance
in Salmonella typhi
* AMR is also emerging in
Shigella spp. and Vibrio
spp.
* VRSA
VIRUSES
* HIV: Resistance to
components of HAART
* HSV: Aciclovir resistance
has emerged
* Influenza: Oseltamivir
resistance
FUNGI
* Azole resistance in
Candida & Aspergillus
spp.
* Candida auris
PARASITES
* Plasmodium falciparum
resistant to chloroquine
-
