Lec16 Pseudomonas aeruginosa Flashcards

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1
Q

What are the lab characteristics of pseudomonas aeruginosa?

A
  • lactose non-fermenter [lactase negative]
  • oxidase positive
  • aerobic [but facultative anaerobe]
  • gram negative
  • bacilli
  • unipolar motility [unipolar flagellum]
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2
Q

Which patients are especially susceptible to pseudomonas aeruginosa infection?

A
  • neutropenic patients [from cancer chemo]
  • patients with severe burns
  • cystic fibrosis
  • patients with diabetes and foot ulcers
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3
Q

What are the sources of pseudomonas and related infections?

A
  • soil, water, plant material, environmental surfaces
  • ## found on medical equipment
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4
Q

What are the virulence factors for p aeruginosa? responsible for adherence? motility? host evasion? iron acquisition? exotonis? exoenzymes? reactive pigments?

A

adherence/motility: pili, flagellum, outer membrane protines

host evasion: LPS [resist complement], proteases [degrade host opsonins, prevent phagocytosis]

iron acquistion: siderophores [pyoverdin, pyochelin]

exotoxins: exotoxin A, leukocidins, phospholipases, hemolysins

other exoenzymes: exoS, exoT, exoU, exoY

reactive pigments: pyocyanin [reactive oxidants]

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5
Q

What are the clinical diseases associated with p. aeruginosa?

A
  • bacteremia
  • endocarditis
  • skin, soft tissue infections
  • skeletal infections
  • ocular infections
  • ear infections
  • respiratory infections
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6
Q

What patients are most likely to get bacteremia from p. aeruginosa?

A
  • IV drug users
  • neutropenic hospitalized pts
  • burn pts
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7
Q

What patients are most likely to get endocarditis from p. aeruginosa?

A

IV drug users

usually right heart

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8
Q

What type of skin/soft tissue infections does p. aeruginosa cause?

A
  • milkd folliculitis
  • infected burn wound with sepsis
  • infected surgical wound or pressure ulcer
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9
Q

What type of skeletal infections does p. aeruginosa cause?

A
  • hematogenous
  • from direct inoculation [foot puncture through sneaker]
  • contiguous spread
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10
Q

What type of ear infections does p. aeruginosa cause?

A
  • swimmers ear to malignant necrotizing otisis externa
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11
Q

What type of respiratory infections does pseudomonas aeruginosa cause?

A

cystic fibrosis, ventilator associated pneumonia

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12
Q

What is a clinical sign of P aeruginosa bacteremia?

A
  • ecthyma gangrenosum
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13
Q

What is pathogenesis of P aeruginosa in eye infection?

A
  • follows trauma [including that from contact lenses]

- get corneal ulcer, endophtalmitis

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14
Q

What is cystic fibrosis?

A
  • autosomal recessive disorder
  • due to mutations in gene encoding CFTR [usually at F508]
  • get abnormal electrolyte transport
  • involves epithelium of airways, gut, exocrine glands
  • marked by chronic lung infection/inflammation
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15
Q

What is the microbiology of chronic infection in CF?

A
  • usually get staph aureus or H. influenzae infection first
  • then over time get p. aeruginosa [classic non-mucoid] infection
  • over time get activation of alg genes and end up with chronic mucoid p. aeruginosa that is more resistant to immune system and to antibiotics
  • in late stage can sometimes get burkholderia cepacia infection
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16
Q

What antibiotics can you use to treat pseudomonas aeruginosa?

A

carboxy- and ureido-penicillins

  • piperacillin [piperacillin/tazobactam]
  • ticarcillin [ticarcillin/clavulanate]
  • mezlocillin

cephalosporins [ceftazidime, cefepime]

carbapenems [imipenem-cilastatin, meropenem, NOT ertapenem]

monobactams [aztreonam]

aminoglycosides [gentamicin, tobramycin, amikacin] [usually not used as single agent except for in UTI]

fluoroquinolones [cipro]

polymyxins [colistin, polymyxin B]

17
Q

What are mech of p. aeruginosa resistance?

A
  • beta lactamases
  • overexpression efflux pumps
  • drug modification
  • altered PBPs
  • mutation of porins
18
Q

What disease are associated with burkholderia cepacia?

A
  • catheter associated bacteremia

- ventilator associated pneumonia

19
Q

What diseases are associated with stenotrophomonas maltophilia?

A
  • catheter associated bacteremia

- ventilator associated pneumonia

20
Q

What do you use to treat s. maltophilia?

A
  • often only trimethoprim/sulfa or quinilones are effective
21
Q

what do you use to treat burkholderia cepacia?

A
  • same drugs as p aeruginosa
22
Q

What are aminoglycosides used to treat?

A
  • aerobic gram negative bacilli [like pseudomonas]
  • some gram positive cocci [enterococcus, staph]

less often

  • myobacteria
  • nocardia
  • tularemia, plague [y. pestis]
23
Q

What is role of aminoglycosides in therapy? Are they more often given alone or in combo?

A
  • rarely they are the primary therapy

- often used for synergy with other drug or to reduce emergence of resistance to primary drug

24
Q

What is distribution of aminoglycosides?

A
  • distributed to extracellular fluid volume
  • poor entry into host cell
  • little CSF/tissue penetration
  • poor oral absorption
25
Q

How are aminoglycosides eliminated?

A

eliminated by glomerular filtration

half life 2-3 hrs

26
Q

What are the 4 primary aminoglycosides used in US?

A
  • gentamicin C
  • tobramycin
  • streptomycin
  • amikacin
27
Q

What is mech of action of aminoglycosides?

A
  • interferes with protein synthesis

- blocks initiation of protein syntehsis

28
Q

What is mech of resistance to aminoglycosides?

A

primary: drug modification

less common: porin protein mutation, ribosomal protein mutation

29
Q

What is use of neomycin?

A

topical use only

30
Q

Are aminoglycosides concentration or time dependent?

A

concentration dependent

31
Q

How big is the post-antibiotic effect of aminoglycosides?

A
  • significant post-antibiotic effect

- means that effect outlasts “effective” serum conc

32
Q

What are the main toxicities associated with aminoglycosides?

A

mainly - nephrotoxicity, ototoxicity

also - neuromuscular blockade [if infused too quickly or in myasthenia gravis]

33
Q

What happens is you do once daily higher dose vs lower dose every 8 hrs for aminoglycoside?

A
  • equivalent efficacy

- lower nephrotoxicity

34
Q

What are the main agents of nosocomial infection?

A
  • respiratory viruses [RSV, parainfluenza, influenza, adenovirus]
  • methicillin-resistant staph aureus
  • vancomycin resistant enterococcus faecium
  • multiresistant gram negative bacilli
  • clostridium difficile
35
Q

Which gram negative important in nosocomial infections?

A
  • enterobacteriaceae
  • pseudomonadaceae
  • other gram neg
36
Q

Where do most nosocomial infections occur?

A
  • burn units
  • newborn ICU
  • medical and surgical ICU
  • oncology units
37
Q

Why do most nosocomial infections occur?

A
  • invasive procedure/insertion of foreign device
  • compromise or destruction of normal barriers
  • susceptibility of hosts
38
Q

What are mech of resistance in hospital associated bacteria?

A
  • beta lactamase productin
  • PBP mutation
  • porin mutation
  • enzymatic modification of drug
  • efflux pumos
  • alteration of drug target
39
Q

What are prinicpals of antibiotic usage to minimize resistance?

A
  • avoid needless use of broad spectrum antibiotics

- use narrowest specturm antibiotic that you think will be effective