Pseudomonas aeruginosa: Difference between revisions
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Pseudomonas aeruginosa
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==Background== |
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===Microbiology=== |
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* Oxidase |
*Oxidase [[Oxidase::positive]], non-fermenting [[Stain::Gram-negative]] [[Shape::bacillus]] |
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=== Definitions of Drug Resistance === |
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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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** 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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* MexAB-OprM efflux pump |
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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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* Inducible AmpC β-lactamase |
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* Plasmid sharing |
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===Mechanisms of Resistance=== |
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= Environment and Infections = |
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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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**Topoisomerase II (gyrA) or IV (parC) point mutations: resistance to [[fluoroquinolones]] |
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===Epidemiology=== |
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* See [Antipseudomonal antibiotics](/Infectious Diseases/Basics/Antimicrobials/Antipseudomonal antibiotics.md) |
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*Refer to [[antipseudomonal antibiotics]] for specific treatment options |
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*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]] |
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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 |
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{{DISPLAYTITLE:''Pseudomonas aeruginosa''}} |
{{DISPLAYTITLE:''Pseudomonas aeruginosa''}} |
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Latest revision as of 15:35, 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
- Broad intrinsic and acquired antibiotic resistance1
- Membrane impermeability
- Decreased or absent OprD porin: resistance to carbapenems (imipenem and meropenem) that may spare other β-lactams
- Membrane changes: resistance to polymixins (colistin)
- Reduced aminoglycoside transport: resistance to aminoglycosides
- Efflux pumps
- MexAB-OprM: resistance to fluoroquinolones and all β-lactams except imipenem
- MexCD-OprJ: resistance to fluoroquinolones and most β-lactams (cefoperazone, cefpirome, cefepime, meropenem) but not imipenem
- MexEF-OprN: resistance to fluoroquinolones and all β-lactams
- MexXY-OprM: resistance to fluoroquinolones, tetracyclines including tigecycline, most β-lactams (but not imipenem or ceftazidime), and aminoglycosides
- β-lactamases
- Derepressed AmpC β-lactamase: resistance to penicillins and cephalosporins (except ceftolozane)
- Acquired carbapenemases such as NDM-1: resistance to essentially all β-lactams
- Aminoglycoside-modifying enzymes: resistance to aminoglycosides
- Target site mutations
- Topoisomerase II (gyrA) or IV (parC) point mutations: resistance to fluoroquinolones
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
- MDR-PA 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
- Difficult-to-treat Pseudomonas aeruginosa is defined as non-susceptibility to all of: piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem, imipenem-cilastatin, ciprofloxacin, and levofloxacin
- Consider any of the following options:
- Amikacin 20 mg/kg IV once, followed by dosing per levels (see Aminoglycosides)
- Cefiderocol 2 g IV 18h infused over 3 hours
- Ceftazidime-avibactam 2.5 g IV q8h infused over 3 hours
- Ceftolozane-tazobactam 3 g IV q8h infused over 3 hours
- Colistin
- Gentamicin 7 mg/kg IV once followed by dosing per levels (see Aminoglycosides)
- Imipenem-relebactam 1.25 g IV q6h infused over 30 minutes
- Plazomicin 15 mg/kg IV once followed by dosing per levels (see Aminoglycosides)
- Polymixin B
- Tobramycin 7 mg/kg IV once followed by dosing per levels (see Aminoglycosides)
- Preference for ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam, as well as cefiderocol if UTI
References
- ^ 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.
