Bacterial Resistance Flashcards
For an antimicrobial agent to inhibit or kill a pathogen, what are a few things that must be done.
- Enter the cell
- Reach the target site of action
- Bind to the target site
- Impair the function
What are the some of the parts in Bacterial Structure?
- Plasmids [most Gram-Negatives]
- Cytoplasmic Membrane
- Cell Wall
- Outer Membrane
- Periplasmic Space
What is important to know about Plasmids in Bacterial Strucutre?
- Extrachromosomal, Double Stranded DNA
- Encodes for genes that are not essential for survival but benefits
- Transferable to other bacteria
What is important to know about the Cytoplasmic Membrane in Bacterail Structure?
- Permeability Barrier that allow certain drugs to pass through
What is important to know about Cell Wall [Peptidoglycan] in Bacterial Structure?
- Gram Positive = THICK; Gram Negative = THIN
- Contains PBPs; very important in Cell Wall synthesis
When talking about the Cell Wall, what is the importance of PBPs?
- 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
What is important to know about the Outer Membrane in Bacterial Structure?
- ONLY in Gram Negatives
- Has Lipopolysacchardies and Porins [hydrophilic channels that permit diffusion]
What is important to know about the Periplasmic Space in Bacterial Sturture?
- Located between the cytoplasmic membrane and outermembrane in Gram Negatives
- Where b-lactamases are located
What are some of the risk factors for Bacterial Resistance?
- Technologic and Societal Changes [board-spectrum antibiotics, Young & Old, Daycare]
- Economics
- Animal Husbandry
- Microbial Characteristics [Rapid Replications, Intrisic Resistance]
- Reservoir
- Overuse
What is Alexander Flemings Warning in 1945?
- Not to have resistance
What are the impacts of Bacterial Resistance?
- Increased Morbidity and Mortality
- Increased diseases
- Increased Cost
What is the difference between Intrinsic Resistance and Acquired Resistance?
- Intrinsic: ALWAYS resistant due to absence of target site or impermeability
- Acqured: was susceptible but BECAME resistant due to mutations or acquisition
When talking about Acquired Resistance, what are some of the Genetic Exchange Mechanisms?
- Conjugation: direct contact [most common]
- Transduction: Transferred by Virus
- Transformation: uptake of “free floating” DNA from dead bacterium
What are the 3 specific Mechansims of resistance?
- Ezymatic Inactivation [most common]
- Alteration of Target sites
- Altered Permeability of bacterial cell
What are the two specific mechanisms of Resistance for Enzymatic Inactivation?
- b-lactamases
- Aminoglycosides-modifying enzymes
What are the Ambler Classifications for b-Lactamases?
- ESBL = CTX-M-15
- Serine Carbapenemases = KPC 1, 2, 3
- Metallo-b-lactamses = VIM-1, IMP-1, NDM-1
- Cephalosporines = AmpC
In what organisms in AmpC normally found in?
- HECK YES Ma’aM
- Hafnia Alvei, Enterobacter Cloacae, Citrobacter Freundii, Klebsiella aerogenes, Yersinia Enterocoloitica, Morganella species, Aeromonas Hydrophila
What is important to know about AmpC b-Lactamases?
- 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]
What does induction mean when dicussing AmpC b-lactamases?
- Gene for b-lactamases in repressed –> inducer –> genes depressed –> increased production
- Remove inducer –> gene repressed –> normal levels
What is the most important labile inducer?
- Cefoxitin
What is Selection of Stably Derepressed Mutants in Ampc b-lactamases?
- 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
What are the drugs that we should use to treat HECK YES Ma’aM Organisms?
- Cefepime
- Carbapenem [meropenem, imipenem, ertapenem]
- Non-b-lactam
What are Extended Spectrum b-lactamases [ESBL] mediated resistance?
- 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
What inhibits and is resistant toward ESBLs?
- Resistant: ceftazidime, cefotaxime, ceftriaxone, aztreonam
- Inhibited: Avibactam, Tazobactam
What is the treatment for ESBLs?
- Carbapenems: DOC [cant use when on valproic acid]
- SMX/TMP
- High dose Pip/Tazo [inferior to Carbapenems]
What is the importance of the Merino Trial?
- Determine therapy with Pip/Tazo is non-inferior to Merpenem [does not support the use]
What is the importance about Carbapenem Resistance?
- Loss of the safest line of defense
- Carbapenem resistant Enterobacterales [CRE] does not mean carbapenemases are present
What are the most clinically relevant Carbapenemases?
- KPC: Klebsiella Pneumoniase Carbapenemases
- Metallo-b-lacamases
- OXA-type - Oxacillinase
What is important to know about KPC within Carbapenemases?
- Serine Carbapenemase
- MOST FREQUENT
- Always plamid mediated
- Inhibited by Avibactam, Vaborbactam, Relebactam
What is important to know about Metallo-b-lactamases within Carbapenemases?
- NDM: New Delhi Metallo-b-lactamases [origin]; VIM: Verona Intergorn; IMP: Imipenem Hydrolyzing
- NOT inhibited by current b-lactams
- Aztronam/avibatam might inhibited it
What is important to know about OXA-Type Oxacillinase within Carbapenemases?
- Most common in europe
- Pre-dominant causes of carbapenem-resistant Acinetobacter Baumannii [CRAB]
What is the treatment for KPC?
- Ceftazidime/Avibactam
- Meropenem.Vaborbactam
- Imipenem/Cilastatin/relebactam
- Cefiderocol [Fetroja]
What is the treatment for Metallo-b-lactamases?
- Aztreonam + Ceftzidime/avibactam
- Cefiderocol
What is the treatment for OXA-type in CRAB?
- High Dose Sulbactam +/- Ampicillin
- Sulbactam/Durlobactam [when HAP/VAP by CRAB]
- Cefiderocol
What is important to know about Aminoglycosode-modifying enzymes?-
- 3 mechanisms: Acetylation, Nucleotidylation, Phosphorylation
- Seen in Enterococci
What are some of the Altered Target Sites in Bacterial Resistance?
- Penicillin Binding Proteins
- Altered Cell Walls
- Ribsomes
- Topoisomerases
What is important to know about Penicillin Binding Proteins in Altered Target Sites?
- 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
