Pseudomonas aeruginosa: Difference between revisions

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Pseudomonas aeruginosa
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== Background ==
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==Background==
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=== Microbiology ===
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===Microbiology===
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* [[Oxidase test::Oxidase-positive]], [[Has fermentation::non-fermenting]] [[Stain::Gram-negative]] [[Cellular shape::bacillus]]
  
   
  ⚫
*Oxidase [[Oxidase::positive]], non-fermenting [[Stain::Gram-negative]] [[Shape::bacillus]]
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=== Mechanisms of Resistance ===
  
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* Broad intrinsic and acquired antibiotic resistance
  
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* Membrane impermeability
  
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* MexAB-OprM efflux pump
  
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* Acquired mutations
  
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* Inducible AmpC β-lactamase
  
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* Plasmid sharing
  
   
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=== Epidemiology ===
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=== Definitions of Drug Resistance ===
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* Loves moist and wet environments
  
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* Causes healthcare-associated infections
  
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** UTI, SSI, bacteremia, HAP, VAP
  
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** Especially common in cystic fibrosis
  
   
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* '''Multidrug resistant (MDR)''' is defined as non-susceptibility to at least 1 antibiotic in at least 3 antibiotic classes (penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapanems)
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== Treatment ==
  
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** Results from decreased OprD, AmpC hyperproduction, upregulation of efflux pumps, and PBP target mutations
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** Carbapenemase production is uncommon but increasing
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* '''Extensively drug-resistant (XDR)''' is resistant to more than one antimicrobial agent in all the antimicrobial categories, except in two or less
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* '''Pan-drug-resistant (PDR)''' is resistant to all antimicrobial agents in all antimicrobial categories
   
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===Mechanisms of Resistance===
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* Refer to [[antipseudomonal antibiotics]] for specific treatment options
  
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* Double coverage (ß-lactam + non-ß-lactam) in cases of severe infection in order to ensure activity against the infection
  
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*Broad intrinsic and acquired antibiotic resistance[[CiteRef::livermore2002mu]]
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*Membrane impermeability
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**Decreased or absent OprD porin: resistance to [[carbapenems]] ([[imipenem]] and [[meropenem]]) that may spare other β-lactams
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**Membrane changes: resistance to polymixins ([[colistin]])
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**Reduced aminoglycoside transport: resistance to [[aminoglycosides]]
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*Efflux pumps
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**MexAB-OprM: resistance to [[fluoroquinolones]] and all [[β-lactams]] except [[imipenem]]
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**MexCD-OprJ: resistance to [[fluoroquinolones]] and most [[β-lactams]] ([[cefoperazone]], [[cefpirome]], [[cefepime]], [[meropenem]]) but not [[imipenem]]
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**MexEF-OprN: resistance to [[fluoroquinolones]] and all [[β-lactams]]
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**MexXY-OprM: resistance to [[fluoroquinolones]], [[tetracyclines]] including [[tigecycline]], most [[β-lactams]] (but not [[imipenem]] or [[ceftazidime]]), and [[aminoglycosides]]
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*β-lactamases
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**Derepressed AmpC β-lactamase: resistance to [[penicillins]] and [[cephalosporins]] (except [[ceftolozane]])
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**Acquired [[carbapenemases]] such as NDM-1: resistance to essentially all [[β-lactams]]
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*Aminoglycoside-modifying enzymes: resistance to [[aminoglycosides]]
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*Target site mutations
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**Topoisomerase II (gyrA) or IV (parC) point mutations: resistance to [[fluoroquinolones]]
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===Epidemiology===
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  ⚫
*Loves moist and wet environments
  ⚫
*Causes healthcare-associated infections
  ⚫
**UTI, SSI, bacteremia, HAP, VAP
  ⚫
**Especially common in cystic fibrosis
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  ⚫
==Treatment==
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  ⚫
*Refer to [[antipseudomonal antibiotics]] for specific treatment options
  +
*Preferred: [[piperacillin-tazobactam]], [[ceftazidime]], [[cefepime]], [[aztreonam]]
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**If repeat testing confirms resistant to carbapenems but susceptibility to other β-lactams (which is most commonly caused by decreased OprD), use an extended infusion of a β-lactam
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*Alternatives: [[meropenem]] or [[imipenem]]
  ⚫
*Double coverage (ß-lactam + non-ß-lactam) in cases of severe infection in order to ensure activity against the infection
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=== Multidrug-Resistant Isolates ===
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* MDR-PA is defined as non-susceptibility to at least 1 antibiotic in at least 3 antibiotic classes (penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapanems)
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** Results from decreased OprD, AmpC hyperproduction, upregulation of efflux pumps, and PBP target mutations
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** Carbapenemase production is uncommon but increasing
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* Difficult-to-treat [[Pseudomonas aeruginosa]] is defined as non-susceptibility to all of: [[piperacillin-tazobactam]], [[ceftazidime]], [[cefepime]], [[aztreonam]], [[meropenem]], [[imipenem-cilastatin]], [[ciprofloxacin]], and [[levofloxacin]]
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* Consider any of the following options:
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** [[Amikacin]] 20 mg/kg IV once, followed by dosing per levels (see [[Aminoglycosides#Dosing|Aminoglycosides]])
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** [[Cefiderocol]] 2 g IV 18h infused over 3 hours
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** [[Ceftazidime-avibactam]] 2.5 g IV q8h infused over 3 hours
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** [[Ceftolozane-tazobactam]] 3 g IV q8h infused over 3 hours
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** [[Colistin]]
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** [[Gentamicin]] 7 mg/kg IV once followed by dosing per levels (see [[Aminoglycosides#Dosing|Aminoglycosides]])
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** [[Imipenem-relebactam]] 1.25 g IV q6h infused over 30 minutes
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** [[Plazomicin]] 15 mg/kg IV once followed by dosing per levels (see [[Aminoglycosides#Dosing|Aminoglycosides]])
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** [[Polymixin B]]
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** [[Tobramycin]] 7 mg/kg IV once followed by dosing per levels (see [[Aminoglycosides#Dosing|Aminoglycosides]])
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*Preference for [[ceftolozane-tazobactam]], [[ceftazidime-avibactam]], and [[imipenem-relebactam]], as well as [[cefiderocol]] if UTI
   
 
{{DISPLAYTITLE:''Pseudomonas aeruginosa''}}
  
{{DISPLAYTITLE:''Pseudomonas aeruginosa''}}

Latest revision as of 11:35, 11 July 2023

Background

Microbiology

  • Oxidase positive, non-fermenting Gram-negative bacillus

Definitions of Drug Resistance

  • Multidrug resistant (MDR) is defined as non-susceptibility to at least 1 antibiotic in at least 3 antibiotic classes (penicillins, cephalosporins, fluoroquinolones, aminoglycosides, and carbapanems)
    • Results from decreased OprD, AmpC hyperproduction, upregulation of efflux pumps, and PBP target mutations
    • Carbapenemase production is uncommon but increasing
  • Extensively drug-resistant (XDR) is resistant to more than one antimicrobial agent in all the antimicrobial categories, except in two or less
  • Pan-drug-resistant (PDR) is resistant to all antimicrobial agents in all antimicrobial categories

Mechanisms of Resistance

Epidemiology

  • Loves moist and wet environments
  • Causes healthcare-associated infections
    • UTI, SSI, bacteremia, HAP, VAP
    • Especially common in cystic fibrosis

Treatment

  • Refer to antipseudomonal antibiotics for specific treatment options
  • Preferred: piperacillin-tazobactam, ceftazidime, cefepime, aztreonam
    • If repeat testing confirms resistant to carbapenems but susceptibility to other β-lactams (which is most commonly caused by decreased OprD), use an extended infusion of a β-lactam
  • Alternatives: meropenem or imipenem
  • Double coverage (ß-lactam + non-ß-lactam) in cases of severe infection in order to ensure activity against the infection

Multidrug-Resistant Isolates

References

  1. ^  D. M. Livermore. Multiple Mechanisms of Antimicrobial Resistance in Pseudomonas aeruginosa: Our Worst Nightmare?. Clinical Infectious Diseases. 2002;34(5):634-640. doi:10.1086/338782.

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