Id - 4-22 - Abx Resistance

Front 1

Acinetobacter

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multridrug resistance in healthcare settings, military, natural disasters

kills peole

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most resistance is mediated by....

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plasmids

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Pan-resistance

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For gram negatives - means it is resistance to antipseudomonal cephs and carbapenems, piperacillin/tazobactam, cipro and levofloxacin

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Extreme drug resistance (XDR)

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resistant to antipseudomonal cephs and carbapenems, piperacillin/tazobactam, cipro and levofloxacin

also aminoglycosides, tigecycline, polymixins.

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ESKAPE bugs

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nosocomial pathogens that have resistance

Enterococcus faecium, staph aureus

Gram (-) now...(most of them...)
Klebsielle pneum, acinetobacter, pseudomonas, enterobacter

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abx that inhibit stages in bacterial replication

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the drugs bind specific bacterial targets and they must reach the target

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penicillins and cephs -

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inhiibt a stage in bac replication

bind to penicillin binding proteins (cross-linkers of bac cell wall. wont work against )

wont work against atypicals (chlamydia) or mycobacteria (e.g. tuberculosis) bc they don't have a cell wall or PBPs

vanco can't get across gram - or lipid bilayer of mycobac so can't affect them! this is intrinsic resistance

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intrinsic vs acquired resistance

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intrinsic - the drug never had a chacne against this bug

acquired - genetic variability (mutations) allowed bacteria to become resistant.

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constitutive resistance vs inducible

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constit - most common - bac mech. is present consistently and essential for bacterial function

inducible resis - culture looks sensitive but then when exposed to abx, the efflux pump, beta lactamase, etc is upregulated. (seen with pseudomonas)

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bacteria replication.....

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is very very quick. so they have more chance of mutation

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examples of single NT base mutations (mech of drug resistance)

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quinolone resistance or evolution of beta lactamases

for this reason, only want to use fluoros against gram (-) bacteria

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Large DNA rearrangements (mech of drug resistance)

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transposable segments that move in cassettes which contains resistance to many drugs - e.g. staph aureus

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aquisition of DNA from another bacteria (final mech of drug resistance)

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plasmids, phages, transposable elements move via conjugation, transduction or transformation.

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Resistance in staph aureus

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Penicillin sens - 10%
Methicillin sens - 60% (beta lactamases)
Hosp-acq MRSA - 30% - modified PBPs
CA-MRSA - 30% - modified PBPs
Vanco intermediate SA - Van gene cassette from enterococcus (rare cases)

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Main ways to survive abx

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altered drug permeability, altered drug targets, inactivation of drug, active efflux.

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strep pneum reistance

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altered PBP (so you must add vancomycin)

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slide 23

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sdoajkf

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drug classes that are victim to beta lactamases

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penicillins, cephs, monobactams (aztreonam), meropenem.

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vanco get resistance against it by...

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modified cell wall targets.

Front 20

mech of resistance against beta lactamase inhibitors (e.g. clavulanate)

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hyperprod of new beta-lactamases resistant to inhibitors.

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mech of resistance against quinolones (cipro) and ex

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altered gyrase/topoisomerases
e.g. pseudomonas

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mech of resistance against rifampin

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altered rna polym binding (e.g. mycobac tuberculosis)

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mech of resistance against 50s inhibitors (macrolides or lincomycins)

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ribosomal rna methylation (e.g. group a strep)

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mech of resistance against 30s inh (tetracyclines or aminoglycosides) - doxycycline or gentamycin

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efflux pump or aminoglycoside modifying enzymes - e.g. salmonella or CoNStaph)

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mech of resistance against bactrim

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drug-insensitive dihydrofolate reductase - e.coli.

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ways to survive abx exposure

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altered drug perm - vancomycin or gram (-)

altered targets (gram+) - e.g. quinolone targets or PBPs

inactivation - betalactamases or aminoglycoside modif enzymes

active efflux (gram -)

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Tx of staph aureus

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issues with beta lactamases and altered PBPs

so use nafcillin or cefazolin
or vancomycin

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tx of strep pneum

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altered PBPs is the issue so use ceftriaxone or vanco

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tx of GAS

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erythryomycin issue so use penicillin or cefazolin

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tx of neisseria

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issue with quinolone resistance so use ceftriaxone

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tx of haemophilus inf

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beta lactamases can be made so use cefuroxime or beta lactam and a beta lactamase inhibitor

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tx of e coli

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membrane permeability and beta lactamase issues

so use ceph with aminoglycoside or quinolone.

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tx of CONStaph

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vanco

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tx of enterococcus

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vnaco

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tx of pseudomonas

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antipseudomonal penicillin or

ceph + aminoglycoside or quinolone (synergy)

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tx of enteric gram -

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often can induce extended spectrum beta lactamases

so use extended spectrum cephalosporin adn aminoglycoide or quinolone

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tx of anaerobes (e.g. bacteriodes fragilis)

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beta lactamases are present so try metronidazole first, then meropenem

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many mouth anaerobes are not susc to...

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penicillin

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what to do when lab tells you a bug is resistant to everything

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get the MIC along with predicted serum level to see which are relatively better and if there is synergy possible.

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principles

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Antibiotic resistance will emerge with time and drug use.
Resistance progresses from low levels to high levels.
Organisms that are resistant to one drug are likely to become resistant to others.
Once it appears, resistance declines slowly, if at all.
One person’s antibiotic use affects others in their environment.

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hwo to rpevent resistance spread

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A. Justify and review frequently the indications for antibiotics in each clinical situation.
B. Use the narrowest spectrum antibiotic possible to remove the selective pressure for the development of resistance.
C. Practice meticulous hand-washing.
D. Infection control measures for those identified with resistant organisms.