Antibiotic Resistance Flashcards
1
Q
Bacterial Resistance
A
- Mutation: small % resistance evoluation
- Acquisition of bacterial resistance is most common
- Transfer of genetic material coding for resistance is plasmid (P) or transposon (T) medicated
- P/T are extrachromosomal pieces of DNA
2
Q
P
A
Replicate within bacterial cell but limited in transfer between classes
3
Q
T
A
Not limited but generally must be attached to chromosome, bacteriophage, or plasmid replication
4
Q
Mechanisms of Resistance
A
Bacteria employ one or more of the basic mechanisms:
- Enzymatic degradation of the antibiotic agents
- Alterations of the targets of antibiotic agents
- Changes in cell wall permeability
- Production of efflux pumps
5
Q
Alterations of Antibiotic Targets
A
- Alteration in PBPs
- Modified cell wall precursors
- Alteration of ribosomal targets
- Alterations in target enzymes
6
Q
S. aureus - Penicillin Resistance
A
- B-lactamase mediated
- Hydrolysis of -cillins
- Inhibited by B-lactamase inhibitors
- Referred to as MSSA: prevalence >95%
7
Q
S. aureus - Oxacillin Resistance
A
- MecA gene encoding PBP 2a - alteration of PBPs (low affinity)
- Affects activity of all B-lactams except Ceftaroline (5th generation cephalosporin)
- Known as MRSA: prevalence 30-50%
8
Q
VISA
A
- Vanco-intermediate S. aureus
- Vanco MIC: 4-8 ug/mL
9
Q
VRSA
A
- Vanco-resistant S. aureus
- Vanco MIC >= 16 ug/mL
- vanA gene noted
- All VRSA have arisen from MRSA
- Usually hospital acquired
- Co-colonization with vanco-resistant E. faecalis has been reported in several cases
10
Q
E. faecalis/faecium First Line Therapy
A
- Ampicillin + Gentamicin or Streptomycin
- Vancomycin + Gentamicin or Streptomycin
- Linezolid or Daptomycin
11
Q
Enterococcal Resistance
A
- Capable of exchanging genetic information with other enterococci and staph.
- Many resistant genes are plasma-mediated with staph origin: B-lactamases, aminoglycoside modifying enzymes
12
Q
Enterococcal Resistance + Drugs
A
- Ampicillin/Penicillin: alteration in PBPs, B-lactamase production
- Aminoglycosides: high-level of aminoglycoside-modifying enzymes
- Vanco: Modified cell wall precursors and vanA gene
13
Q
S. Pneumoniae Resistance + Drugs
A
- Penicillins: decreased affinity for PBPs
- Macrolides: methylation of 23S rRNA and efflux pumps (lower level of resistance)
- Clindamycin: methylation of 23S rRNA
- Fluoroquinolones: reduced binding affinity for topoisomerase and gyrase
14
Q
S. pneumoniae - Overcoming Resistance
A
- High dose PCNs
- Increased doses of Macrolides (efflux pump)
- Else, alternative agents
15
Q
MLS Resistance
A
- Macrolide-Lincosamide-Streptogramin resistance
- Methylating enzymes that modify adenine residues on 23S ribosomal RNA
- Methylated RNA can’t be binded
- Can be Constitutive or inducible
16
Q
Constitutive
A
rRNA methylase is always produced
17
Q
Inducible
A
- Methylase is produced in the presence of an inducing agent
- Erythromycin is an effective inducer but clindamycin is weaker
18
Q
Ribosomal Alterations
A
- Aminoglycosides: mutation in 30s ribosomal subunit (streptomycin)
- Linezolid: G257 6T mutation in domain V of 23S rRNA gene (can possibly revert back after antimicrobial pressure is removed)
19
Q
Enzymatic Degradation
A
- B-lactamases: classical enzymes, ESBLs, AmpC, carbapenemases, metallo-enzymes
- Aminoglycosides: acetylase
20
Q
B-lactamase
A
- Over 340 different types
- Based on biochemical and genetic properties
- Plasmid vs chromosomally mediated
- Constitutive or inducible production based on B-lactam exposure
21
Q
TEM/SHV B-lactamases
A
- TEM-1, TEM-2, and SHV-1 (Classical)
- Resistant to ampicillin, amoxicillin, early gen. cephalosporins
- Later generation cephs resist hydrolysis
- Inhibitors protect parent B-lactam compound
- Produced by most enterobacteriaceae
22
Q
ESBLs
A
- TEM or SHV-type (mutants of classicals)
- Minor amino acid substitutions
- Hydrolyze 3rd, 4th gen. cephalosporins and aztreonam
- Inhibited by B-lactamase inhibitors
- Carbapenems and cephamycins are spared
23
Q
CTX-M, OXA-Type
A
- Type of ESBLs
- CTX-M hydrolyze cefotaxime more efficiently than ceftazidime
- OXA-type ESBLs mainly in P. aeruginosa
24
Q
AmpC B-lactamases
A
- Normally produced in low levels by many organisms
- High-level production can cause resistance to cephamycins, 1st/3rd gen. cephalosporins, monobactams, B-lactamase inhibitors
- DON’T hydrolyze cefepime or carbapenems
- Plasmid mediated or chromosomal
25
Q
Cephamycins
A
- Cefotetan
- Cefoxitin
26
Q
Bacteria w/ Inducible AmpC Resistance (Chromosomal)
A
S - Serratia marcescens P - Pseudomonas aeruginosa, Proteus A - Acinetobacter baumannii C - Citrobacter E - Enterobacter
27
Q
Good AmpC Inducers
A
- Cefoxitin
- Imipenem
- Ampicillin
- Clavulanate
28
Q
ESBL Characteristics
A
- Class A
- BLI inhibited
- Plasmid based
- Not chromosomal
- Not inducible
- Present in all enterobacteriaceae
29
Q
AmpC Characteristics
A
- Class C
- Not BLI inhibited
- Plasmid or chromosomal based
- Inducible (when chromosomal)
- SPACE = > chromosomal and enterobacteriaceae in plasmid involvement
30
Q
Treatment of ESBL/AmpC Producers
A
- Carbapenems: frequently associated with treatment success
- Avoid cephalosporins against ESBL
- Can use cefepime for AmpC
- ESBL carried on plasmid is also resistant to Bactrim, aminoglycosides, and fluoroquinolones
31
Q
Carbapenemase
A
- CRE
- Organisms of the enterobacteriaceae family with a number of transmissible genetic elements with multiple resistant genes
- EX: KPC, NDH-1, VIM, and IMP
- Resistant to all 3rd gen. cephalosporins and not susceptible to carbapenems
32
Q
CRE Significance
A
- CRE associated with 40-50% mortality rates
- Usually carry other genes that resistance to commonly used antimicrobials
- Can spread resistance horizontally to common commensal organisms
- Treatment options: Colistin and Tigecycline
33
Q
P. Aeruginosa
A
- Resistant to carbapenems
- Related to overproduction of AmpC, less OprD porin channel production, and activation of efflux systems
34
Q
Cell Wall Permeability
A
- Alterations in porins or channels
- Associated with Gram-negative bacteria
- Resistant to macrolides, B-lactams, aminoglycosides, TMP, tetracyclines, and quinolones
35
Q
Production of Efflux Pumps
A
- Method of resistance
- Resistant to tetracyclines, macrolides, B-lactams, quinolones
36
Q
Altered Permeability + Chromosomal Mutations
A
- Decrease size of OM porin
- Increase in amount of smaller narrow OM porins
- Decrease in specific type of OM porin
- Alteration in proteins of OM porin producing lower permeability
- Loss of specific entry channels
37
Q
Quinolone Resistance
A
- Two mechanisms: alteration in target enzymes or impaired access to target enzymes (pumps/porins)
- Chromosomal mutations
- Recent plasmid-mediated resistances have emerged to stop quinolone binding with DNA gyrase
38
Q
AMG Resistance
A
- Reduced uptake/cell permeability - P.aeruginosa and gram “-“ bacteria
- Altered ribosome binding sites
- Enzymatic modification - most common with highest level of resistance
39
Q
AMG + Enzymatic Modifications
A
- Genes causing modifications usually found on plasmids and transposons
- Usually found in gram “-“ bacilli with multiple genes
- Three types of modifying enzymes: AAC, ANT, and APH
40
Q
AAC
A
- N-acetyltransferases
- AMG modifying enzyme
- catalyzes acetyl-CoA-dependent acetylation of an amino group
41
Q
ANT
A
- O-Adenyltransferases
- AMG modifying enzyme
- catalyzes ATP-dependent adenylation of hydroxyl group
42
Q
APH
A
- O-phosphotransferases
- AMG modifying enzyme
- Catalyzes ATP-dependent phosphorylation of a hydroxyl group
