Lec16 Pseudomonas aeruginosa Flashcards
What are the lab characteristics of pseudomonas aeruginosa?
- lactose non-fermenter [lactase negative]
- oxidase positive
- aerobic [but facultative anaerobe]
- gram negative
- bacilli
- unipolar motility [unipolar flagellum]
Which patients are especially susceptible to pseudomonas aeruginosa infection?
- neutropenic patients [from cancer chemo]
- patients with severe burns
- cystic fibrosis
- patients with diabetes and foot ulcers
What are the sources of pseudomonas and related infections?
- soil, water, plant material, environmental surfaces
- ## found on medical equipment
What are the virulence factors for p aeruginosa? responsible for adherence? motility? host evasion? iron acquisition? exotonis? exoenzymes? reactive pigments?
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]
What are the clinical diseases associated with p. aeruginosa?
- bacteremia
- endocarditis
- skin, soft tissue infections
- skeletal infections
- ocular infections
- ear infections
- respiratory infections
What patients are most likely to get bacteremia from p. aeruginosa?
- IV drug users
- neutropenic hospitalized pts
- burn pts
What patients are most likely to get endocarditis from p. aeruginosa?
IV drug users
usually right heart
What type of skin/soft tissue infections does p. aeruginosa cause?
- milkd folliculitis
- infected burn wound with sepsis
- infected surgical wound or pressure ulcer
What type of skeletal infections does p. aeruginosa cause?
- hematogenous
- from direct inoculation [foot puncture through sneaker]
- contiguous spread
What type of ear infections does p. aeruginosa cause?
- swimmers ear to malignant necrotizing otisis externa
What type of respiratory infections does pseudomonas aeruginosa cause?
cystic fibrosis, ventilator associated pneumonia
What is a clinical sign of P aeruginosa bacteremia?
- ecthyma gangrenosum
What is pathogenesis of P aeruginosa in eye infection?
- follows trauma [including that from contact lenses]
- get corneal ulcer, endophtalmitis
What is cystic fibrosis?
- 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
What is the microbiology of chronic infection in CF?
- 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
What antibiotics can you use to treat pseudomonas aeruginosa?
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]
What are mech of p. aeruginosa resistance?
- beta lactamases
- overexpression efflux pumps
- drug modification
- altered PBPs
- mutation of porins
What disease are associated with burkholderia cepacia?
- catheter associated bacteremia
- ventilator associated pneumonia
What diseases are associated with stenotrophomonas maltophilia?
- catheter associated bacteremia
- ventilator associated pneumonia
What do you use to treat s. maltophilia?
- often only trimethoprim/sulfa or quinilones are effective
what do you use to treat burkholderia cepacia?
- same drugs as p aeruginosa
What are aminoglycosides used to treat?
- aerobic gram negative bacilli [like pseudomonas]
- some gram positive cocci [enterococcus, staph]
less often
- myobacteria
- nocardia
- tularemia, plague [y. pestis]
What is role of aminoglycosides in therapy? Are they more often given alone or in combo?
- rarely they are the primary therapy
- often used for synergy with other drug or to reduce emergence of resistance to primary drug
What is distribution of aminoglycosides?
- distributed to extracellular fluid volume
- poor entry into host cell
- little CSF/tissue penetration
- poor oral absorption
How are aminoglycosides eliminated?
eliminated by glomerular filtration
half life 2-3 hrs
What are the 4 primary aminoglycosides used in US?
- gentamicin C
- tobramycin
- streptomycin
- amikacin
What is mech of action of aminoglycosides?
- interferes with protein synthesis
- blocks initiation of protein syntehsis
What is mech of resistance to aminoglycosides?
primary: drug modification
less common: porin protein mutation, ribosomal protein mutation
What is use of neomycin?
topical use only
Are aminoglycosides concentration or time dependent?
concentration dependent
How big is the post-antibiotic effect of aminoglycosides?
- significant post-antibiotic effect
- means that effect outlasts “effective” serum conc
What are the main toxicities associated with aminoglycosides?
mainly - nephrotoxicity, ototoxicity
also - neuromuscular blockade [if infused too quickly or in myasthenia gravis]
What happens is you do once daily higher dose vs lower dose every 8 hrs for aminoglycoside?
- equivalent efficacy
- lower nephrotoxicity
What are the main agents of nosocomial infection?
- respiratory viruses [RSV, parainfluenza, influenza, adenovirus]
- methicillin-resistant staph aureus
- vancomycin resistant enterococcus faecium
- multiresistant gram negative bacilli
- clostridium difficile
Which gram negative important in nosocomial infections?
- enterobacteriaceae
- pseudomonadaceae
- other gram neg
Where do most nosocomial infections occur?
- burn units
- newborn ICU
- medical and surgical ICU
- oncology units
Why do most nosocomial infections occur?
- invasive procedure/insertion of foreign device
- compromise or destruction of normal barriers
- susceptibility of hosts
What are mech of resistance in hospital associated bacteria?
- beta lactamase productin
- PBP mutation
- porin mutation
- enzymatic modification of drug
- efflux pumos
- alteration of drug target
What are prinicpals of antibiotic usage to minimize resistance?
- avoid needless use of broad spectrum antibiotics
- use narrowest specturm antibiotic that you think will be effective
