2 organisms of concern for GP resistance
- acquired resistance
- chromosomal mutation
- due to antibiotic pressure
- i.e. during DNA replication, copying error occurs and genes are deleted partially or completely
- acquired resistance
- acquisition of new genetic material from other resistant organisms
- occur btwn strains of species or different bacterial species
- conjugation, transduction, transformation
- i.e. S. aur resistance to methicillin and vanco
- extrachromosomal DNA (separate from chromosomal DNA)
- can replicate independently
- circular and double stranded
in the plasmid, carry the resistant gene
infections caused by staph aureus?
- blood stream infxn
- pneumonia, sinusitis (hospital)
why is staph aur resistant to pcn?
- due to production of extracellular enzyme, penicillinase
- hydrolyze the amide bond of b-lactam ring of pcn and ampicillin
- carried by a plasmid
why is staph aur resistant to oxacillin and methicillin?
- b/c mecA resistant gene
- encodes PBP2a which has dec affinity for oxacillin and other b-lactam drugs
- alteration of target site
where is mecA gene carried?
mobile genetic element, SCC mec (staphylococcus cassette chromosome)
which types of mec gene are MDR?
II and III
which mec gene has resistance only in mecA gene?
which mecA gene are for hospital MRSA?
I, II and III
which replicates faster? hospital MRSA or MSSA?
MSSA is faster
which 2 mecA genes are for community MRSA?
IV and V
which is more similar to MSSA? hospital vs. community MRSA
why would community MRSA have more efficient trasnfer of resistance than hospital?
b/c small in size, replicates more rapidly, greater fitness of CA-MRSA mecIV gene
how do you dx community acq MRSA?
- diagnosis made in outpatient setting or positive MRSA within 48h of hospital admission
- no hx of MRSA or colonization
- no hx of prior year of hospitalization, dialysis, surgery, NH/SNF/hospice
- no permanent indwelling catheter, medical device
can you have comm-acq MRSA if you have catheter?
- medical device either
can you have comm-acq MRSA if you have dialysis?
- neither surgery nor hospitalization
CA-MRSA acquired a novel genetic element called ___ via ___ transmission, possibly from which bug? this is genomic sequencing of ___
- arginine catabolic mobile element (ACME)
- horizontal transmission
- staph epidermis
- USA 300 strain
which has more frequent toxin production? hospital vs. community MRSA? name of the toxin?
- panton-valentine leucocidin toxin (PVL): almost always produced in community
HA-MRSA has enterotoxin __ and __.
CA-MRSA has enterotoxin __ and __.
toxic shock syndrome toxin (TSST-1) may be produced by which MRSA? (hosp vs. comm)
what are the clinical syndromes?
- septic shock, necrotizing pneumonia, cSSTI
activity of panton-valentine leucocidn gene?
it is associated with what kind of infxn?
which MRSA has this (hosp vs comm)?
- damage cell by making holes in membrane of erythrocyte and leukocyte. leads to massive tissue necrosis
- necrotic skin, pneumonia
- community MRSA
PVL toxin has a relationship with which type of mec gene?
HA-MRSA has MDR. CA-MRSA has resistance limited to _____.
b-lactam and erythromycin
HA-MRSA has USA strain ___ , while CA-MRSA has __ and ___.
infections due to CA-MRSA?
- necrotizing fasciitis
- pneumonia (rare but very high mortality)
infections due to HA-MRSA?
- blood stream infxn
risk factors for MRSA?
- homeless youth
- military recruits
- competitive atheletes
- GI disease
- native american, alaska native, pacific islander
- tetracyclin (doxy, mino)
- FQ (levo, moxi)
- bactrim (2 DS bid)
- linezolid, vanco
- rifampin (must use as combo tx)
- vanco, lin, dapto
bactrim is for ___ MRSA. available formulation? bacteriostatic or cidal?
advantages of clindamycin for CA MRSA?
- distribute well into skin and skin structure
- inhibit toxin production and virulence factor in SA
disadvantage of clindamycin for CA MRSA?
- inducible resistance: must have D test (erythro(R) and clinda(S) MRSA can still induce clinda(R) during therapy so cannot use)
- clostridium dificile associated diarrhea
what should you do before initiating clindamycin for CA MRSA? name of the resistance gene? explain
- MLSb(ribosomal subunit alteration): cross resistance of macrolide/lincosamide/streptogramin
- this is induced by erythromycin
- erythro(R) and clinda(S) MRSA can still induce clinda(R) during therapy so cannot use
is FQ used commonly for CA MRSA? how about HA MRSA?
- CA: often avoided b/c rapid resistance
- HA: nope. inc incidence of MRSA colonization
downside of linezolid if prolonged use?
- bone marrow suppression
- optic neuritis
mechanism of resistance of VISA?
thicken organism's cell wall (diff mechanism from VRSA so they are not linked)
can you use vanco for VISA? why?
- VISA thickens organism's cell wall. vanco gets trapped in the outer layer and cannot enter cytoplasm thus cannot carry its abx action
is hVISA (heterogeneous) susceptible to vanco?
- but contain subpopulation of organisms with borderline vanco MIC btwn S and I.
mechanism of resistance for VRSA? relate it with vanco mechanism
- acquired a vanA vancomycin resistant gene from e.faecalis by conjugal transfer of plasmid DNA (located on transposon)
- vanco directly binds cell wall precursors and prevents cross linking of D-ala-D-ala. VRSA makes D-ala-D-lac so vanco binds weakly.
- (basically produce different amino acid)
is VRSA evolved from VISA?
- different mechanism of resistance
mech of resistance for FQ for MRSA?
- spontaneous mutation causing change to amino acid in the enzymes essential for DNA replication
- place in the enezyme, QRDR: ParC on topoisomerase IV and GyrB on DNA gyrase (clinically significant)
- rarely efflux pump (you can overcome with high dose)
clindamycin mech of resistance gene? where are they carried?
- erm genes
- MSSA-erm (C) carried on plasmid
- MSSA-erm (A) carried by transposon
which enterococcus has more resistance? faecium vs. faecalis?
- faecalis is very sensitive
mech of resistance of enterococcus?
- vanA and vanB
- alter target for vancomycin from D-ala-D-Ala to D-ala-D-lactate
if you have significant anti-enterococcal activity, does it promote VRE colonization?
- if lacking, then promotes VRE
if there is a high anaerobic activity, does it promote VRE?
- if low, then it does not promote VRE colonization
if high concentration secretion in human bile, VRE colonization is promoted. t or f?
- if low concentration, it does not promote VRE colonization
is ceftriaxone great for VRE?
it's great for bilirary but risk for VRE colonization.
which is better for VRE? timentin vs. zosyn
does extended spectrum cephalo increase VRE colonization?
does oral vanco increase VRE colonization?
does metronidazole increase VRE colonization?
yes, b/c has anaerobic coverage
does timentin increase VRE colonization?
does zosyn increase VRE colonization?
tx options for VRE?
dual MOA of telavancin
- inhibit cell wall synthesis
- disrupt membrane barrier function
- bactericidal, conc dep
what does telavancin cover?
- MRSA, MSSA, streptococcus, enterococcus faecalis
- off label: VISA, VRSA
how is the t/2 of telavancin?
it's long~ advantage
SE of telavancin?
- foamy urine
- taste disturbance, inf-related reaction, insomnia, nausea
tigecycline treats which infxn? what organisms does it cover?
- cSSTI, CAP, IA
- GP: MRSA, MSSA, e.faecalis
- in vitro VRE
linezolid covers which organisms?
- MRSA, MSSA, e.faecium
- e.faecalis, e. faecium in vitro
which infxn does linezolid cover?
cSSTI, uSSTI, CAP, HAP
dapto is FDA approved for which organisms? how about in vitro?
- FDA: MSSA, MRSA, e.faecalis, streptococcus
- in vitro: VRE
can dapto cover VISA?
- thickened cell wall on organism hindered penetration of dapto into cell membrane, esp if staph has high MIC to vanco.
- need high dose
MRSA resistance to linezolid and dapto has to do with...? (MOR)
reduced binding of drug to target site
oritavancin has strong activity vs. ___
- staph aureus
- active vs. VRE, VRSA
oritavancin can cover which infxn?
advantage of oritavancin?