Pseudomonas aeruginosa in 500 words (and 5 minutes): A lesson in dynamic evolutionary pressure

How can I miss you, if you won’t go away?” – song by Dan Hicks and the Hot Licks

Particularly challenging in the chronically hospitalized, the immunocompromised, and those with cystic fibrosis, P. aeruginosa (Figure 1) has found a niche in intensive care units around the world. P. aeruginosa is a very common, encapsulated, gram-negative rod that has been recognized for its highly evolved antibiotic resistance. As a facultative anaerobe, it is ubiquitous in the environment – presenting in soil, skin flora, and touch surfaces – and thrives on moist surfaces. Its versatility allows it to inhabit many harsh environments, flourish in damaged tissues (e.g., lungs, urinary tract), and form tenacious biofilms on implants. As such, P. aeruginosa is implicated in 9-10% of hospital-acquired infections. Interestingly, pseudomonal growth in the respiratory tract can be virtually asymptomatic until the development of a biofilm, overwhelming the primary cilia movement of mucus, which is a phenomenon contributing to the morbidity associated with cystic fibrosis lung infection.

The genome of P. aeruginosa is comparatively large and plasmids are often present, many facilitating antibiotic resistance. Its multidrug resistance is predominately related to the development of three separate efflux pump mechanisms, particularly the MexAB-OprM multidrug efflux pump that effectively negates the activity of penicillins, cephalosporins, and aminoglycosides 1. In addition, target site mutations in the GyrA topoisomerase subunit, a target of the quinolone class, may result in drug treatment failure. Carbapenem resistance results from loss of the outer membrane porin channel (OprD).

Its innovative adaptability results in high risk for antibiotic-resistant infection later in a patient’s hospital course, including ventilator-associated pneumonia (VAP), particularly after earlier exposure to antibiotics 2. P. aeruginosa comprises 10-20% of isolates in VAP in the United States and is often multidrug-resistant. Most patients will have an identifiable risk factor for P. aeruginosa hospital acquired pneumonia, such as prolonged mechanical ventilation, advanced age, antibiotics at admission, and local prevalence of P. aeruginosa 3. Additional risk factors include structural abnormalities of the lung or a history of repeated exacerbations of chronic obstructive pulmonary disease. Gram negative antibiotic coverage has been extensively studied in VAP. Empiric regimens have included cephalosporins, antipseudomonal penicillins, and carbapenems, among others. Broadly, the research evidence has not suggested major differences between drug classes in mortality, adverse events, and other clinically relevant endpoints for the treatment 4. This concept suggests that local environmental factors may play a considerable role in mortality associated with multidrug resistant organisms, such as P. aeruginosa. Clinicians should therefore familiarize themselves with their local institutional antibiogram to most effectively treat potentially antimicrobial-resistant pathogens. Furthermore, guidelines recommend that two antipseudomonal agents from two different classes should be utilized in patients with risk factors for antibiotic resistance (Table 1). Avoiding early inadequate antibiotic therapy is highly associated with improved outcomes in P. aeruginosa pneumonia in critically ill patients 5.

In conclusion, P. aeruginosa is an organism notable for its innovative and opportunistic abilities to wreak havoc in our intensive care environments. Treatment should focus on its rapid identification (including risk stratification), understanding local patterns of drug resistance, and treatment by tailored antibiograms to ensure favorable outcomes in our critically ill patients.

Figure 1: Pseudomonas aeruginosa. ID#23249 2019 Jennifer Oosthuizen CDC/Antibiotic Resistance Coordination and Strategy Unit. Public Health Image Library.

Table 1: Risk Factors for the development of Multidrug-Resistant Infection
Risk factors – MDR VAP

  1. Prior antibiotic use within 90 days
  2. Features of septic shock at time of VAP
  3. Features of acute respiratory distress prior to VAP
  4. >5 days of hospitalization prior to VAP
  5. Renal replacement therapy prior to VAP onset
Risk factor for MDR P. aeruginosa

  1. Prior antibiotic use within 90 days of VAP

Adapted from: Kalil A, Metersky ML, Klompas M et al. Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society (2016)

  1. Hancock RE, Speert DP. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and impact on treatment. Drug Resist Updat. 2000;3(4):247-55. doi: 10.1054/drup.2000.0152.
  2. Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157(2):531-9. doi: 10.1164/ajrccm.157.2.9705064.
  3. Venier AG, Gruson D, Lavigne T, Jarno P, L'Hériteau F, Coignard B, et al. Identifying new risk factors for Pseudomonas aeruginosa pneumonia in intensive care units: experience of the French national surveillance, REA-RAISIN. J Hosp Infect. 2011;79(1):44-8. doi: 10.1016/j.jhin.2011.05.007.
  4. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases. 2016;63(5):e61-e111. doi: 10.1093/cid/ciw353.
  5. Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, et al. Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med. 2013;39(4):682-92. doi: 10.1007/s00134-013-2828-9.


Zyad J. Carr, M.D., FASA1
1Yale University School of Medicine, New Haven, Connecticut