View source for Pseudomonas aeruginosa

==Background==
===Microbiology===

*Oxidase [[Oxidase::positive]], non-fermenting [[Stain::Gram-negative]] [[Shape::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 resistance[[CiteRef::livermore2002mu]]
*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#Dosing|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#Dosing|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#Dosing|Aminoglycosides]])
** [[Polymixin B]]
** [[Tobramycin]] 7 mg/kg IV once followed by dosing per levels (see [[Aminoglycosides#Dosing|Aminoglycosides]])
*Preference for [[ceftolozane-tazobactam]], [[ceftazidime-avibactam]], and [[imipenem-relebactam]], as well as [[cefiderocol]] if UTI

{{DISPLAYTITLE:''Pseudomonas aeruginosa''}}
[[Category:Gram-negative bacilli]]