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Infectious Disease 2 > Enterobacterales, Pseudomonas & Other Opportunistic Gram-Neg Organisms and Associated Resistance Mechanisms > Flashcards

Enterobacterales, Pseudomonas & Other Opportunistic Gram-Neg Organisms and Associated Resistance Mechanisms Flashcards

1
Q

What are the pathogens that are on the WHO list of priority pathogens?

A
  • E. faecium
  • S. aureus
  • K. pneumoniae
  • A. baumonii
  • P. aeruginosa
  • Enterbacterales spp.
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2
Q

What are the four major types of antibiotic resistance mechanisms?

A
  • Loss of porin channels
  • Increased efflux pumps
  • Enzymatic degradation
  • Change in the binding site
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3
Q

Give an example of an intrinsic gene and what pathogen has it?

A

SHV-1 gene–> encodes for beta-lactamases
* Klebsiella pneumoniae has this as an constitutive expression which results in aminopenicillin resistance

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4
Q

Lateral or horizontal gene transfer

A

Acquisition of large segments of foreign DNA carried by resistance (R) plasmids, bacteriophages, naked sequences of DNA, or specialized transposable genetic elements known as integrative and conjugative elements (ICE)
* Acquired

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5
Q

What are some enzymes that are acquired and what bacteria are they in?

A

Extended-spectrum beta-lactamases (ESBL) [constitutive expression]
* include plain penicillin, aminopenicillin & additional penicillin that have extended; maybe even 1st and 2nd generation cephalosporins (plasmid acquisition)
* Relevant bactera:
* E.coli
* Klebsiella species
* Proteus species

Carbapanemase (Klebsiella producing carbapenemase, KPC) [constitutive expression]
* acquired by plasmids
* Relevant bacteria: Klebsiella species

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6
Q

Stable de-pression

A

Exposure to antibiotics can cause the inducible gene to be continuously expressed and if the expression is persistent, it can cause the bacteria to be resistant to many antibiotics

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7
Q

What is the gene is acquired and inducible?

A

AmpC gene–> AmpC beta-lactamase

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8
Q

What are some relevant bacteria that has the AmpC enzyme?

A
  • Serratia species
  • Pseudomonas species
  • Acinetobacter species
  • Citrobacter species
  • Enterobacter cloacae, Klebsiella aerogenes
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9
Q

Ambler Classification of Beta-lactamases

Class A, C, and D

A

Hydrolyze the beta-lactam ring through a serine residue at their active site

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10
Q

Ambler Classification of beta-lactamases

Class B

A

Metallo-Beta-Lactamases (MBLs) that use zinc to break the amide bond

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11
Q

What is the most common ESBL in the US?

A

CTX-M (especially CTX-M-15)

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12
Q

What is used as proxy for ESBL testing?

A

Nonsusceptibility to ceftriaxone however organisms not susceptible to ceftriaxone for reasons other than ESBL production may be falsely presumed to be ESBL-production

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13
Q

Carbapenems Resistant Enterobacterales

A

The CDC defines CRE as members of the Enterobacterales order resistant to at least one carbapenem antibiotic or producing a carbapenemase enzyme

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14
Q

What is the most common carbapenemases?

A

KPC = Klebsiella pneumoniae carbapenemases (NOT ONLY produced by Klebsiella)

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15
Q

What are the straight facultative gram negative anaerobes?

A

Enterobacterales
* E.coli
* Klebsiella spp
* Proteus spp
* Enterobacter, Citrobacter, Serratia spp

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16
Q

What are the straight gram negative aerobes?

A
  • Legionella pneumophilia
  • Pseudomonas aeruginosa
  • Acinetobacter baumanii
  • Stenotrophomonas maltophilia
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17
Q

What are the curved spherical cocci gram negative?

A

Neisseria meningitidis

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18
Q

What are the curved pleomorhpic (cocco bacilli) gram negative?

A
  • Haemophilus influenzae
  • Acinetobacter baumanii
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19
Q

Enterobacterales

A
  • Includes related genera of short, non-spore forming, facultative anaerobes
  • Gram-neg rods
  • Most ferment lactose, ferment glucose, reduce nitrate, are catalase (+) and oxidase (-)
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20
Q

What are the bacteria are enterobacterales?

A
  • Escherichia
  • Klebsiella
  • Proteus
  • Enterobacter
  • Citrobacter
  • Serratia
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21
Q

What is the microbiology of E.coli?

A
  • Gram-neg rod
  • Motile (most): flagella
  • Pili
  • Aerobic, facultative anaerobe
  • Ferment lactose (fast)
  • Do NOT split urea
  • Do NOT produce H2S
  • Endotoxin (LPS)
  • Exotoxins (most)
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22
Q

What is the epidemiology of E.coli?

A

Reservoir: Human and animal intestines

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23
Q

What does E.coli cause?

A
  • UTIs #1 cause
  • Neonatal meningitis (#2 cause after S. agalactiae)
  • Sepsis #1 cause
24
Q

What gene do some E.coli isolates encode for?

A

Beta-lactamases TEM-1 which inactivates aminopenicillins but not 1st generations cephalosporins

24
Q

What is the microbiology of Klebsiella species?

A
  • Ferment lactose
  • Most produce highly mucoid colonies due to luxuriant polysaccharide capsule
  • Non-motile
25
Q

What are the common species of Klebsiella?

A
  • Klebsiella pneumoniae (more common in community infections)
  • Klebsiella oxytoca
  • Klebsiella variicola
  • Klebsiella (Enterobacter) aerogenes
26
Q

What are some resistance mechanisms of Klebsiella?

A

Enzymatic degradation
* Intrinsic: Chromosomal gene encodes penicillin-specific beta-lactamase
* Acquired–via multiple drug resistance (MDR) plasmids
* Beta-lactamases
* Extended spectrum beta-lactamases (ESBL)
* AmpC type beta-lactamases (notable for Klebsiella [Enterobacter] aerogens)
* Carbapenemases production (Klebsiella pneumoniae)

27
Q

What is the microbiology of Proteus?

A
  • Facultative anaerobe
  • Found in soil, water, and fecal contaminated material
  • Inhabits human GI tract
  • **“Swarm” over moist agar plates **
  • **Non-lactose fermenting **
  • FImbriae/pili–aid in colonizing the urinary tract
  • Flagellae–motility along urinary tract
28
Q

What is Proteus intrinsically resistance to?

A

Tetracyclines, Nitrofurantoin, polymyxins (colistin)

29
Q

Proteus mirabilis

A

Produces urease
* Hydrolyzes urea in urine to ammonium hydroxide increasing pH
* Precipitation of Mg, calcium, and ammonium forms triple phosphate kidney stone (struvite)
* Can lead to renal calculi, UTIs, hydronephrosis, abscess due to obstruction
Indole (-)

30
Q

Proteus vulgaris

A
  • Decomposes tryptophan via the enzyme “Tryptophanase”
  • Indole is one of the end products formed after this deamination/hydrolysis of tryptophan
  • Produces urease
  • Intrinsic resistance to ampicillin/amoxicillin, 1st and 2nd generation cephalosporins
31
Q

What infections are caused by Proteus mirabilis?

A

Commonly associated with UTIs in the community setting

32
Q

What infections are caused by Proteus vulgaris?

A

Hospital acquired infections: Pneumonia, wound infections, bacteremia (urine source), septicemia

33
Q

What is the resistance of Proteus mirabilis?

A

While many community strains are susceptible to aminopenicillins and 1st gen cephs
* Some harbor plasmids that encode TEM-1 beta-lactamases–> inactivates aminopenicillins but not 1st generation cephs
* Healthcare assoc strains: frequently MDR

34
Q

What is the microbiology of Enterobacter, Citrobacter, Serratia?

A
  • Facultative anaerobes
  • Enterobacter & Citrobacter–> lactose fermenters, inhabit human GI tract
  • Serratia marcescens–**rare lactose fermenters; characteristic red pigment (prodigiosin) **
35
Q

What is Enterobacter, Citrobacter, Serratia intrinsically resistance to?

A

Ampicillin/amoxicillin, 1st generation cephs and many 2nd cephs due to chromosomal AmpC beta-lactamases; exceptions is Citrobacter koseri

36
Q

What is Enterobacter, Citrobacter, Serratia inducibly resistance to?

A

With 3rd generation cephalosporins
(less of a concern for Serratia)

37
Q

What is Enterobacter cloacae resistant to?

A

Amoxicillin/clavulante and ampicillin/sulbactam

38
Q

What is Serratia marcescens IR resistant to?

A
  • Amoxicillin/clavulante
  • Ampicillin/sulbactam
  • Nitrofurantoin
39
Q

What is the microbiology of Pseudomonas?

A
  • Gram negative rod (arranged in pairs)
  • Aerobic (“obligate”)
  • Does NOT ferment lactose
  • Oxidase positive
  • Motile
  • Fruity, grape-like fragrance
40
Q

What is the virulence mechanism of Pseudomonas Aeruginosa?

A
  • Adhesions (flagella, pili, LPS, alginate)
  • Toxins (Exotoxin A–disrupts cellular protein synthesis, immunosuppressive)
  • Enzymes–> tissue damage
41
Q

Alginate

A

Mucoid exopolysaccharide, results in protective capsule (from antibiotics and phagocytes)
* Patients with cystic fibrosis esp. prone
* Pseudomonas adhesion virulence mechanisms

42
Q

What is the resistance mechanism of Pseudomonas?

A
  • Mutation in penicillin binding proteins (PBP)
  • Beta-lactamases production (hyperproduction of AmpC and/or Carbapenemases)
  • Decreased outer membrane porin expression (OprD)
  • Extended spectrum beta-lactamases
  • Efflux pump regulation
43
Q

What is the treatment options for Pseudomonas?

A
  • Aminoglycosides (AMGs)
  • Aztreonam
  • Cefepime
  • Cefiderocol
  • Ceftazidme
  • Ceftazidme/avibactam
  • Ceftolozane/tazobactam
  • Ciprofloxacin, levofloxacin, delafloxacin
  • Imipenem/cilastatin
  • Imipenem/cilastatin + relebactam
  • Meropenem & Mero/vaborbactam
  • Piperacillin-tazobactam
  • Polymixin E (Colistin) and Polymixin B
44
Q

What is P.aeruginosa with Difficult to Treat Resistant (DTR) non-susceptible to?

A
  • Piperacillin-tazobactam
  • Ceftazidime, cefepime
  • Aztreonam
  • Meropenem, imipenem/cilastatin
  • Ciprofloxacin, levofloxacin
45
Q

Acinetobacter

A
  • Strict aerobes, oxidase-negative, gram-negative coccobacilli
  • Ubiquitous saprophytes
    * Survive on moist (mechanical ventilation equipment) and dry surfaces (human skin)
  • Normal oropharyngeal flora in some healthy people, proliferates during hospitalization
46
Q

What are the two groups of Acinetobacter and what are their differences?

A
  • A. baumanii (glucose-oxidizing)-more common cause of human infection
  • A. lwoffii, A. haemolyticus (non-glucose oxidizing)
47
Q

Who are the patients at risk for acinetobacter species?

A
  • Those receiving broad-spectrum antbx, past surgery, on mechanical ventilatoin
48
Q

What is the drug of choice for Acinetobacter?

A

Ampicillin/sulbactam (sulbactam is active)

49
Q

How do you treat carbapenem-resistant Acinetobacter baumanii (CRAB)?

A
  • Often indicates MDR
    Combination treatment with high dose ampicillin/sulbactam + 2nd active agent recommended (polymyxin, high dose tigecycline/minocycline)
50
Q

Stenotrophomonas maltophilia

A
  • Gram-negative rods
  • Non-fermenters
  • Opportunistic pathogens
51
Q

Who do infections of Stenotrophomonas maltophilia occur in?

A
  • Debilitated patients
  • Impaired host-defense mechanisms
  • Prolonged inactive antibiotics
  • Common infections (bacteremia, pseudomonas)
52
Q

What are drug options for Stenotrophomonas maltophilia?

A
  • Preferred: SMX/TMP, minocycline
  • Alternatives: Levofloxacin, tigecycline, cefiderocol, or as alternative ceftazidime-avibactam+aztreonam
53
Q

Burkholderia

A
  • Gram-negative bacillus
  • Colonize moist environmental species
  • Non-fermenters of lactose
  • Opportunistic pathogens
54
Q

What are the two clinically relevant species of Burkholderia?

A
  • B. cepacian complex
  • B. pseudomallei (meliodosis), and B. gladioli
55
Q

B. cepacia complex

A

Aggressive pulmonary disease w/ high mortality in
* Cystic fibrosis
* Chronic granulomatous disease (CGD)
* Primary immunodeficiency, defective WBCs

56
Q

What are the drug options for Burkholderia?

A

Varies by species
* Includes SMX/TMP, ceftazidme, meropenem, minocycline, cipro/levofloxacin

Infectious Disease 2 (7 decks)

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