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43 Cards in this Set

  • Front
  • Back
3 MOR against beta-lactams
-beta lactamase production
-PBP alterations
-porin changes (carbapenems)
define induction wrt beta lactamases
extent to which an antibiotic causes beta-lactamase expression

strong v. weak
define stability wrt beta lactamases
susceptibility of an antibiotic to beta-lactamase activity

stable v. labile
what is the ideal combination of stability and induction
weak/stable
1 weak/stable Abx
cefepime (big gun)
for SPACE bugs
4 weak/labile Abx
-2nd gen cephalosporins
-3rd gen cephalosporins
-acylureidopenicililins
-aztreoname
2 strong/stable Abx
imipenem
meropenem
2 strong/labile Abx
1st gen cephalosporin
ampicillin
2 MORs for macrolides and lincosides (clindamycin)
"mef" gene produces macrolide efflux pump

"erm" alters rRNA binding site, MLSb phenotype for both macrolides and lincosides
FQs MOR
active efflux

DNA binding site alteration (gyrase, topoisomerase)
tetracyclines MORs
active efflux

rRNA binding site alteration
vancomycin MOR
alteration of peptidoglycan precursors
2 ways bacteria can become resistant
-mutations are transferred between bacteria
-due to selective pressure, rare resistant strains dominate upon replication
2 ways to monitor resistance
phenotypic resistance
genotypic resistance
define phenotypic resistance
-MIC
-elevation in MIC = resistance
-degree of elevation sometimes indicates response resistance mechanism
define genotypic resistance
-genetic sequencing to ID mutations
-not often performed in clinical practice
-$$$
3 breakpoints
susceptible
intermediate
resistant
define susceptible breakpoint
MIC of isolate at or below breakpoint

high likelihood of infection responding to normal dose of antimicrobial
define intermediate breakpoint
MIC of isolate above susceptible breakpoint but not above resistant breakpoint

less likelihood of infection responding to normal dose, but may respond to increased dose

AKA dose-dependent
define resistant breakpoint
MIC of isolate above intermediate breakpoint

higher likelihood of clinical failure if tested agent is used
5 limitations of breakpoints
-based on limited clinical evidence
-assume proper dosing of Abx
-breakpoints don't exist for some bacteria don't exist
-do different MIC values within a susceptibility category mean the same thing?
-what does "I" mean?
3 types of susceptibility
national
local
patient-specific
2 ways to tell if resistance is being underestimated
-D-test
-hidden (genetic) mechanisms not detected by MIC
4 ways to prevent resistance
-prevent infection
-effective diagnosis and treatment
-optimize Abx use
-prevent transmission
8 ways to control infections
-vaccination
-limiting use of catheters and other invasive devices
-infection control
-hygiene
-proper storage of infectious fluids
-accurate diagnosis of infection
-surveillance of resistance
-proper and effective antimicrobial use
6 risk factors for S. pneumoniae
-prone to otitis media
-old/young age
-HIV infection, nosocomial pneumonia
-prior hospitalization
-recent and/or repeated Abx use
-recent beta-lactam, SMX/TMP use
2 components of proper antibiotic use
"appropriate" use
- (susceptible)

"adequate" use
-agent with favorable activity
-favorable regimen and duration
3 antimicrobial use strategies
blast them - combo therapy

fool them - cycling

stop irritating them - antimicrobial restriction
describe combination therapy
-additivity or synergy to improve kill
-minimize resistance by using agents with unique resistance mechanisms
-no evidence to suggest this actually works
describe antibiotic cycling
"crop rotation"
-resistance appears to lessen, but returns
-many methodologic details remain unresolved
-works best in a closed environment
-multidrug resistance makes success impossible?
describe antibiotic restriction
-use of each antibiotic can lead to particular resistance problems
-FQ use = carbapenem resistance
-cephalosporine use = VRE
-restrict inappropriate/unnecessary use
-effects poorly understood
the biggest driver of unnecessary antibiotic use is
upper respiratory tract infections
otitis media spontaneously resolves, so should only be used when...
age up to 2 years with certain diagnosis

(uncertain diagnosis if <6 mo)
4 ways to improve or regulate Abx use
-prescriber education
-standard order forms
-formulary restrictions, PA programs
-pharmacy substitution/switches
what does ESKAPE stand for
E - VRE
S - MRSA
S - Streptococcus pneumoniae
K - ESBL-producing E. coli, Kleb
K - carbapenemase-producing Kleb
A - Acinetobacter baumannii
P - Pseudomonase aeruginosa
E - Enterobacter species
describe VRE
Enterococcus faecium > E. faecalis
-3rd most frequent cause of nosocomial bloodstream infections
-current vanco resistance rate is 60%
-little clinical data exists to prove efficacy of newer agents (linezolid, daptomycin, tigecycline)
describe S. aureus and mef-mediated resistance
EFFLUX of macrolides only
-results in low-level macrolide resistance
-clindamycin or a macrolide can be used
describe S. aureus erm-mediated resistance
RIBOSOMAL MODIFICATION
-affects all macrolides AND clindamycin
-results in high-level resistance (dramatic increase in MIC)
-cannot use a macrolide or clindamycin
describe S. pneumoniae and FQs
moxifloxacin is a superior agent in class
describe S. pneumoniae in otitis media
PRSP (penicillin resistant SP)
DRSP (drug resistant SP)

use high-dose amoxicillin to maximize PD to overcome resistance
describe ESBL-producing E. coli, Klebsiella species
ESBL = extended spectrum beta lactamase
-BLIs effectiveness is questionable
-MDR usually present
-difficult to detect by susceptibility testing
-if a cephalosporin is used, treatment failure will usually result

USE CARBAPENEMS
describe P. aeruginosa
role of piperacillin: a ureidoPCN w/ activity against P. aeruginosa

role of tazobactam: BLI

addn of tazobactam to piperacillin doesn't result in enhanced activity because tazobactam is not active against the particular beta lactamase produced
describe Enterobacter species
-may produce inducible beta-lactamases
-organism doesn't express beta-lactamase until it's exposed to a beta-lactam
-this type of beta-lactamase is not inhibited by beta-lactamase inhibitors

USE CARBAPENEMS OR CEFEPIME