Intro to ID Part 2 Flashcards
What color are gram-positive bacteria in a gram stain?
Purple
What color are gram-negative bacteria in a gram stain?
Red/pink
What color are atypical bacteria in a gram stain?
Do not stain
What are acid-fast bacilli?
Resistant to acids/ethanol based decolorization procedures
Gram-positive morphology
-Most medically important pathogens are cocci rather than bacilli
-Gram-positive bacilli should be interpreted with clinical context
Which gram-positive bacteria appear in clusters?
Staphylococcus
Which gram-positive bacteria appear in pairs/chains?
Streptococci and enterococci
Which gram-positive bacteria are catalase positive?
Staphylococcus
Which gram-positive bacteria are catalase negative?
Streptococcus and enterococcus
Gram-negative morphology
Bacilli predominant pathogen
What do oxidase tests tell you about gram-negative bacteria?
Help distinguish between enteric vs. non-enteric lactose fermenters
What are fastidious organisms?
-Slow growers
-Require special supplemental media
What is the difference between gram-positive and gram-negative?
Gram-positive has a thick wall while gram-negative has a thin wall
What are penicillin-binding proteins?
-Enzymes vital for cell wall synthesis, cell shape, and structural integrity (transpeptidases)
-Numbered according to molecular weight
-Differ from one bacterial species to another
-Binding to PBPs 1A, 1B, 2 and 3 result in bactericidal effect
-Transpeptidase most important PBP
Definition of intrinsic resistance
Always resistant to given antibiotic
Mechanism of intrinsic resistance
-Absence of target site
-Bacterial cell impermeability
Definition of acquired resistance
Initially susceptible but develop resistance due to some mechanism
Mechanism of acquired resistance
-Mutation in bacterial DNA (spontaneously vs selective pressure)
-Acquisition of new DNA (chromosomal or extrachromosomal [plasmid])
Plasmid definition
-Self-replicating, extrachromosomal DNA
-Transferable between organisms
-One plasmid can encode resistance to multiple antibiotics
Transposon definition
-“Jumping genes”
-Genetic elements capable of translocating from one location to another
-Move from plasmid to chromosome or vice versa
-Single transposon may encode multiple determinants
Phages definition
Viruses that can transfer DNA from organism to organism
Conjugation definition
-Direct contact or mating via sex pili
-Most common
-DNA shared via mobile genetic elements (MGE), such as plasmids or transposons
Transduction definition
Transfer of genes between bacteria by bacteriophages (viruses)
Transformation definition
-Transfer or uptake of “free floating” DNA from the environment
-DNA is integrated into host DNA
What are beta-lacatamases
Enzymes that hydrolyze beta-lactam ring by splitting amide bond (inactivates drug)
Classification systems for beta lactamases
-Ambler class
-Bush-Jacoby-Medeiros
How are beta-lactamases classified based on the ambler classification system?
Classified according to amino-acid structure (class A-D)
How are beta-lactamases classified based on the Bush-Jacoby-Medeiros classification system?
Classified according to functional characteristics
What are the two types of beta-lactamases
-Serine beta-lactamases: serine residue at active site
-Metallo-beta-lactamases (MBL): zinc residue at active site
Ambler class A beta-lactamases
-Narrow-spectrum beta-lactamases
-Extended-spectrum beta-lactamases (ESBL)
-Serine carbapenemases
Ambler class B beta-lactamases
Metallo-beta-lactamases
Ambler class C beta-lactamases
Cephalosporinases
Ambler class D beta-lactamases
OXA-type
What are extended-spectrum beta-lactamases?
-Plasmid-mediated enzymes that hydrolyze most penicillins, cephalosporins, and monobactams
-Organisms with ESBL gene often harbor additional resistance genes
Most common extended-spectrum beta-lactamase enzyme
CTX-M
What organisms is the ESBL enzyme most prevalent in?
-E. Coli
-Klebsiella pneumoniae/oxytoca
-Proteus mirabilis
Treatment options for extended-spectrum beta-lactamase enzyme
-Treatment of choice: carbapenems
-Non-beta-lactam antibiotics are an option depending on the infection source and susceptibility
-Piperacillin/tazobactam is an option for urinary source only
What is carbapenemase?
-Most frequent cause of carbapenem-resistant enterobacterales (CRE)
-Resistant to entire beta-lactam class
Most common carbapenemase enzyme
-Klebsiella pneumonia carbapenamse (KPC)
-Plasmid-mediated enzyme; KPC-2 and KPC-3 most common variants
What bacteria is carbapenemase enzyme found in?
-K. pneumoniae
-K. oxytoca
-E. coli
-E. cloacae
-E. aerogenes
-P. mirabilis
Treatment options for carbapenemases
-Beta-lactam with beta-lactamase inhibitor: ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam
-Non-beta-lactam: Plazomicin, eravacycline, omadacycline
What are metallo-beta-lactamase
-Confer resistance to all beta-lactams except monobactams (aztreonam)
-Harbor additional antibiotic-resistance genes to other antimicrobial classes
Most common metallo-beta-lactamase enzyme
New Delhi MBL (NDM)
Metallo-beta-lactamases treatment options
-Limited
-Not inhibited by any beta-lactamase inhibitor
-Cefiderocol; aztreonam + ceftazidime/avibactam
What organisms is metallo-beta-lactamases in?
-P. aeruginosa
-Acinetobacter spp.
-Enterobacterales
What are OXA-Type enzymes?
Large heterogenous group often accompanied by other beta-lactamase classes
What organisms are OXA-Type enzymes found in?
-Acinetobacter baumanii
-Pseudomonas aeruginosa
-Some enterobacterales such as klebsiella pneumonia
OXA-Type treatment options
-Extremely limited
-Cefiderocol
-Sulbactam/durlobactam
Mechanism of AmpC
Inducible via chromosomally encoded genes
Which beta-lactamase inhibitors can inhibit AmpC?
-Inhibited by newer beta-lactamase inhibitors: avibactam, vaborbactam, relebactam
-Not inhibited by older beta-lactamase inhibitors (clavulanic acid, tazobactam, sulbactam)
What organisms is AmpC present in?
-Hafnia alvei
-Enterobacter cloacae
-Citrobacter freundii
-Klebsiella aerogenes
-Yersinia enterocolitica
Strong AmpC inducers with high susceptibility to AmpC hydrolysis
-Penicillin G
-Ampicillin
-First generation cephalosporins (cefazolin)
-Cefoxitin
Weak AmpC inducers with high susceptibility to AmpC hydrolysis
-Second generation cephalosporins
-Third generation cephalosporins (ceftriaxone)
-Piperacillin/tazobactam
-Aztreonam
Strong AmpC inducers with low susceptibility to AmpC hydrolysis
Carbopenems
Weak AmpC inducers with low susceptibility to AmpC hydrolysis
Cefepime
Treatment of AmpC
-Cefepime
-Carbapenems
-Non-beta-lactams (fluoroquinolones, trimethoprim/sulfamethoxazole, tetracyclines)
What are aminoglycoside-modifying enzymes?
Most common method of aminoglycoside resistance
Three mechanisms of aminoglycoside-modifying enzymes
-Acetylation
-Nucleotidylation
-Phosphorylation
Aminoglycoside-modifying enzyme mechanism
Modify aminoglycoside structures by transferring the indicated chemical group to a specific side chain -> impairs cellular uptake and/or binding to ribosome
What is a cell wall precursor?
Mechanism of vancomycin resistance in Enterococci species
Cell wall precursor mechanism
-Vancomycin binds to D-Alanine-D-Alanine terminus of peptidoglycan precursors
-Resistance alters D-ala-D-ala to D-ala-D-lac or D-ala-D-ser
-Mediated by VanA or VanB gene -> most common
-Produces vancomycin enterococcus
Vancomycin resistance treatment
Daptomycin or linezolid
PBP alteration mechanism
Decreased ability of PBPs for antibiotic or change in amount of PBP produced by bacteria
Which bacteria has altered PBPs?
Methicillin-resistant staphylococcus aureus
Which gene expression causes alterations in PBPs?
mecA gene
Treatment for PBP alterations
-Ceftaroline
-Ceftobiprole
-Vancomycin
-Daptomycin
-Linezolid
How do PBP alterations effect streptococcus pneumoniae?
Confers penicillin and cephalosporin resistance
What is ribosomal target site alteration?
Responsible for macrolide resistance in S. pneumoniae
Which gene is responsible for ribosomal target site alterations?
ermB gene
Which antibiotics are ribosomal target site alterations resistant to?
-Clindamycin
-Aminoglycosides in gram negatives
Which antibiotics are DNA gyrase/topoisomerase IV alterations resistant to?
Fluoroquinolones in gram-negative and S. pneumoniae
What is the mechanism of efflux pumps?
-Actively transport antibiotics OUT of periplasmic space
-Overexpression can lead to a high level of resistance
Which bacteria do efflux pumps play an important role in?
-P. aeruginosa against carbapenems
-S. pneumoniae against macrolide antibiotics
What are porin channels
-Porin channels are hydrophilic diffusion channels
-Smaller, more hydrophilic antibiotics pass easier than larger, hydrophobic antibiotics
How do mutations effect porins?
Mutations result in loss of specific porins leading to antibiotics resistance
What bacteria are porin mutations most commonly seen?
-Enterobacterales
-Carbapenem-resistant P. aeruginosa
