Bacterial Resistance Flashcards

1
Q

For an antimicrobial agent to inhibit or kill a pathogen, what are a few things that must be done.

A
  • Enter the cell
  • Reach the target site of action
  • Bind to the target site
  • Impair the function
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2
Q

What are the some of the parts in Bacterial Structure?

A
  • Plasmids [most Gram-Negatives]
  • Cytoplasmic Membrane
  • Cell Wall
  • Outer Membrane
  • Periplasmic Space
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3
Q

What is important to know about Plasmids in Bacterial Strucutre?

A
  • Extrachromosomal, Double Stranded DNA
  • Encodes for genes that are not essential for survival but benefits
  • Transferable to other bacteria
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4
Q

What is important to know about the Cytoplasmic Membrane in Bacterail Structure?

A
  • Permeability Barrier that allow certain drugs to pass through
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5
Q

What is important to know about Cell Wall [Peptidoglycan] in Bacterial Structure?

A
  • Gram Positive = THICK; Gram Negative = THIN
  • Contains PBPs; very important in Cell Wall synthesis
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6
Q

When talking about the Cell Wall, what is the importance of PBPs?

A
  • Vital for Cell Wall Synthesis, Cell Shape, Structure
  • PBPs 1A, 1B, 2, 3 = Bactericidal
  • Transpoptidase is the most important in the final step of cell wall cross linkages
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7
Q

What is important to know about the Outer Membrane in Bacterial Structure?

A
  • ONLY in Gram Negatives
  • Has Lipopolysacchardies and Porins [hydrophilic channels that permit diffusion]
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8
Q

What is important to know about the Periplasmic Space in Bacterial Sturture?

A
  • Located between the cytoplasmic membrane and outermembrane in Gram Negatives
  • Where b-lactamases are located
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9
Q

What are some of the risk factors for Bacterial Resistance?

A
  • Technologic and Societal Changes [board-spectrum antibiotics, Young & Old, Daycare]
  • Economics
  • Animal Husbandry
  • Microbial Characteristics [Rapid Replications, Intrisic Resistance]
  • Reservoir
  • Overuse
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10
Q

What is Alexander Flemings Warning in 1945?

A
  • Not to have resistance
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11
Q

What are the impacts of Bacterial Resistance?

A
  • Increased Morbidity and Mortality
  • Increased diseases
  • Increased Cost
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12
Q

What is the difference between Intrinsic Resistance and Acquired Resistance?

A
  • Intrinsic: ALWAYS resistant due to absence of target site or impermeability
  • Acqured: was susceptible but BECAME resistant due to mutations or acquisition
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13
Q

When talking about Acquired Resistance, what are some of the Genetic Exchange Mechanisms?

A
  • Conjugation: direct contact [most common]
  • Transduction: Transferred by Virus
  • Transformation: uptake of “free floating” DNA from dead bacterium
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14
Q

What are the 3 specific Mechansims of resistance?

A
  • Ezymatic Inactivation [most common]
  • Alteration of Target sites
  • Altered Permeability of bacterial cell
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15
Q

What are the two specific mechanisms of Resistance for Enzymatic Inactivation?

A
  • b-lactamases
  • Aminoglycosides-modifying enzymes
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16
Q

What are the Ambler Classifications for b-Lactamases?

A
  • ESBL = CTX-M-15
  • Serine Carbapenemases = KPC 1, 2, 3
  • Metallo-b-lactamses = VIM-1, IMP-1, NDM-1
  • Cephalosporines = AmpC
17
Q

In what organisms in AmpC normally found in?

A
  • HECK YES Ma’aM
  • Hafnia Alvei, Enterobacter Cloacae, Citrobacter Freundii, Klebsiella aerogenes, Yersinia Enterocoloitica, Morganella species, Aeromonas Hydrophila
18
Q

What is important to know about AmpC b-Lactamases?

A
  • Organisms that have the AmpC gene causing production of this b-lactamase
  • NOT inhibited by older b-lactamases [Clav, Tazo, Sulbactam] only NEWER ones [Avibactam, Vaborbactam, Relebactam]
19
Q

What does induction mean when dicussing AmpC b-lactamases?

A
  • Gene for b-lactamases in repressed –> inducer –> genes depressed –> increased production
  • Remove inducer –> gene repressed –> normal levels
20
Q

What is the most important labile inducer?

A
  • Cefoxitin
21
Q

What is Selection of Stably Derepressed Mutants in Ampc b-lactamases?

A
  • May develop with 3rd gen Cephalosporins
  • Population is most inducible cells, but as the labile inducer acts the inducable cells are killed and the depressed cells survive and dominate
22
Q

What are the drugs that we should use to treat HECK YES Ma’aM Organisms?

A
  • Cefepime
  • Carbapenem [meropenem, imipenem, ertapenem]
  • Non-b-lactam
23
Q

What are Extended Spectrum b-lactamases [ESBL] mediated resistance?

A
  • ESBLs: plasmid-mediated enzymes that hydorlyze penicillins and cephalosporins that evolved by mutations [TEM-1/2 or SHV-1]
  • Most common is Klebsiella and E.Coli
24
Q

What inhibits and is resistant toward ESBLs?

A
  • Resistant: ceftazidime, cefotaxime, ceftriaxone, aztreonam
  • Inhibited: Avibactam, Tazobactam
25
Q

What is the treatment for ESBLs?

A
  • Carbapenems: DOC [cant use when on valproic acid]
  • SMX/TMP
  • High dose Pip/Tazo [inferior to Carbapenems]
26
Q

What is the importance of the Merino Trial?

A
  • Determine therapy with Pip/Tazo is non-inferior to Merpenem [does not support the use]
27
Q

What is the importance about Carbapenem Resistance?

A
  • Loss of the safest line of defense
  • Carbapenem resistant Enterobacterales [CRE] does not mean carbapenemases are present
28
Q

What are the most clinically relevant Carbapenemases?

A
  • KPC: Klebsiella Pneumoniase Carbapenemases
  • Metallo-b-lacamases
  • OXA-type - Oxacillinase
29
Q

What is important to know about KPC within Carbapenemases?

A
  • Serine Carbapenemase
  • MOST FREQUENT
  • Always plamid mediated
  • Inhibited by Avibactam, Vaborbactam, Relebactam
30
Q

What is important to know about Metallo-b-lactamases within Carbapenemases?

A
  • NDM: New Delhi Metallo-b-lactamases [origin]; VIM: Verona Intergorn; IMP: Imipenem Hydrolyzing
  • NOT inhibited by current b-lactams
  • Aztronam/avibatam might inhibited it
31
Q

What is important to know about OXA-Type Oxacillinase within Carbapenemases?

A
  • Most common in europe
  • Pre-dominant causes of carbapenem-resistant Acinetobacter Baumannii [CRAB]
32
Q

What is the treatment for KPC?

A
  • Ceftazidime/Avibactam
  • Meropenem.Vaborbactam
  • Imipenem/Cilastatin/relebactam
  • Cefiderocol [Fetroja]
33
Q

What is the treatment for Metallo-b-lactamases?

A
  • Aztreonam + Ceftzidime/avibactam
  • Cefiderocol
34
Q

What is the treatment for OXA-type in CRAB?

A
  • High Dose Sulbactam +/- Ampicillin
  • Sulbactam/Durlobactam [when HAP/VAP by CRAB]
  • Cefiderocol
35
Q

What is important to know about Aminoglycosode-modifying enzymes?-

A
  • 3 mechanisms: Acetylation, Nucleotidylation, Phosphorylation
  • Seen in Enterococci
36
Q

What are some of the Altered Target Sites in Bacterial Resistance?

A
  • Penicillin Binding Proteins
  • Altered Cell Walls
  • Ribsomes
  • Topoisomerases
37
Q

What is important to know about Penicillin Binding Proteins in Altered Target Sites?

A
  • Altered PBP = decreased binding affinity
  • Methicillin resistance in S. Aureus [PBP 2a or 2’ = mecA gene]
  • Penicillin and Cephalosporin resistance in S. Pneumoniae
  • Addition of b-lactamase inhibitor is ineffective