Antimicrobial use, stewardship, and resistance Flashcards
What is the mechanism behind why staph aureus is no longer susceptible to cloxacillin or oxacillin?
Chromosomal mutation 🡪 altered penicillin binding protein (PBP2a) with decreased affinity for methicillin (and oxacillin, and other beta lactams) 🡪 not transferrable between bacteria
How is MRSA bacteremia investigated?
Identify source and extent of infection; eliminate and debride other sites of infection
Repeat blood c/s 2-4 days after initial +ve c/s, and as needed thereafter to document clearance of bacteraemia
Echocardiogram (2DE) for all pts w bacteraemia (TEE (transoesophageal) preferred over TTE (transthoracic)) 🡪 evaluate for infective endocarditis
Evaluate for valve replacement (if IE is the source). To be considered if:
- Vegetation > 10 mm
- ≥ 1 embolic event
- Severe vascular insufficiency
- Valvular perforation
- Decompensated heart failure
- Perivascular/myocardial abscess
- New heart block
How is MRSA bacteremia managed?
Vancomycin is an abx with therapeutic drug monitoring (TDM) when given systemically (IV)
Uncomplicated bacteraemia: 2 weeks minimum. Considered uncomplicated if:
- No infective endocarditis (IE)
- No implanted prosthesis (e.g. prosthetic valves, cardiac devices, arthroplasties)
- -ve follow-up blood c/s for MRSA after 2-4 days
- Defervescence within 72h of therapy
- No evidence of metastatic sites of infection (e.g. spine, joints)
- Not immunocompromised (e.g. neutropenia)
Complicated bacteraemia: 4-6 weeks (if do not meet above criteria)
what is the drug of choice against vancomycin resistant enterococci (VRE)?
linezolid
what antibiotics appear active in vitro but not active in vivo for vancomycin resistant enterococci (VRE)?
Cephalosporins, aminoglycosides (except HLAR screen), clindamycin, Bactrim
What does ESBL (extended spectrum b-lactamases) confer resistance to?
penicillins + first-gen + second-gen + third gen cephalosporins) + aztreonam,
Where is ESBL (extended spectrum b-lactamases) found?
Enterobacteriaceae (GNR), e.g. E coli, Klebsiella pneumoniae, Proteus mirabilis
what is the drug of choice against Enterobacteriaceae (GNR), e.g. E coli, Klebsiella pneumoniae, Proteus mirabilis
- carbapenems, especially for serious infections
- Note that even though BLIs (e.g. clavulanate, tazobactam) can block/inhibit ESBLs in vitro (such that the pathogen is BL-BLI susceptible in vitro), this may not be reliable in serious infections 🡪 DOC is carbapenems
what does inducible cephalosporinases (AmpC b-lactamases) give resistance to?
- AmpC mediates resistance to all currently available beta-lactams (penicillins, first, second, third-gen cephalosporins, aztreonam) with the exception of the carbapenems and perhaps cefepime
- Use of third-gen cephalosporins for infections caused by certain Enterobacteriaceae can induce production of a chromosomally encoded AmpC beta-lactamase 🡪 in vivo treatment failure
Where is inducible cephalosporinases found?
Enterobacter, Serratia, Citrobacter freundi, Aeromonas, Proteus vulgaris (NOT mirabilis), Providencia, Morganella morganii
What is the drug of choice against inducible cephalosporinases?
carbapenems, especially for serious infections
what do CRE (Carbapenem resistant Enterobacteriaceae) confer resistance to?
Carbapenem-hydrolysing beta-lactamases that confer resistance to penicillins, 1st-4th gen cephalosporins, BL-BLI combinations, carbapenems
What are the 4 classes of CRE (Carbapenem resistant Enterobacteriaceae)?
Class A: the most clinically important of the Class A carbapenemases is the K. pneumoniae carbapenemase (KPC) group
Class B: require the presence of zinc for activity (and hence are referred to as metallo-beta-lactamases [MBL])
- New Delhi metallo-beta-lactamase (NDM-1); concern that the gene encoding this MBL is an important emerging resistance trait
Class C
Class D: also referred to as OXA-type enzymes because of their preferential ability to hydrolyse oxacillin (rather than penicillin)
what is the choice of abx against CRE (Carbapenem resistant Enterobacteriaceae)?
Antibiotic options are limited: tigecycline, polymyxin B, polymyxin E (colistin), fosfomycin PO (latter only indicated in cystitis/lower UTI and is not appropriate for urosepsis)
Often combination regimen
What are the anti- pseudomonal agents?
Beta lactams
- Penicillins: piperacillin/tazobactam (pip/tazo), ticarcillin/clavulanate (ticar/clav)
- Cephalosporins: ceftazidime (3rd gen), cefepime (4th gen)
- Carbapenems: imipenem, meropenem (but NOT ertapenem)
- Monobactams: aztreonam
- Aminoglycosides: amikacin, gentamicin, tobramycin
- Quinolones: ciprofloxacin, levofloxacin
- Polymyxins: polymyxin B, polymyxin E
