Pseudomonas aeruginosa

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