This patient was diagnosed with severe community-acquired pneumonia (CAP) due to P. aeruginosa, which progressed to septic shock quickly. It was complicated by secondary hematogenous CNS infection and MODS involving cardiovascular, hematologic, central nervous, and gastrointestinal systems. During treatment, the pathogen developed resistance to carbapenems quickly and the antibiotic regimen was adjusted accordingly. The patient ended up with symptomatic improvement and was discharged from hospital, though unilateral structural lung damage and multiple cavities remained.
In CAP, P. aeruginosa is rarely identified as the pathogenic agent, accounting for only 0.4–6.9% in reported cases of CAP requiring hospitalization [2, 3] and 1.8–8.3% in CAP requiring ICU admission [4,5,6,7,8]. It is very rare in previously healthy patients since P. aeruginosa usually causes infections in patients who have lung structural change, are immunocompromised, or have other specific risk factors. In the English-language literature reported from 1966 to 2000, Todd F  et al. identified only 11 publications describing a total of 13 cases.
Most P. aeruginosa-caused CAP is seen in patients with structural lung diseases, chronic obstructive pulmonary disease (COPD) or cystic fibrosis. Therefore, the 2007 American Thoracic Society (ATS) / Infectious Diseases Society of America (IDSA) guidelines recommended empirical treatment against P. aeruginosa in community-acquired pneumonia (CAP) patients with the following specific risk factors: 1) structural lung disease, like bronchi, 2) recurrent exacerbations of COPD requiring corticosteroid/antibiotic treatment, 3) antibiotic use before admission,4) immunocompromised status. However, by analyzing the data of 402 cases, ORIOL SIBILA et al.  found that current risk factors for CAP due to P. aeruginosa in the CAP guidelines identified only one-third of the patients admitted with CAP due to P. aeruginosa, with the other two-thirds undetected. They also found that chronic heart failure, cerebrovascular disease, advanced age and smoking were risk factors for CAP due to P. aeruginosa. Catia Cillóniz et al. [2, 11] found that malnutrition was another important risk factor for P. aeruginosa-caused CAP. Several studies [12, 13] also found that fatal P. aeruginosa pneumonia in previously healthy patients was associated with contaminated hot tubs. Influenza may be a risk factor for P. aeruginosa infection, there are some reports [14, 15] of P. aeruginosa co-infection with influenza A (H1N1). Influenza viral infection contributes to respiratory epithelial cell dysfunction and death through disruption of protein synthesis and induction of apoptosis, allowing for increased bacterial adherence and invasion .
Compared to pneumonia caused by other pathogens, P. aeruginosa CAP exhibits rapid progression, high severity and poor prognosis. P. aeruginosa CAP usually has a higher CURB-65 score and pneumonia severity index (PSI) than pneumonia caused by other pathogens, with mortality approximately 18–61% [17, 18]. In severe P. aeruginosa CAP, mortality of those who developed progressive septic shock and MODS can reach as high as 50–100% . In death cases, Todd F  reported a median time of 11 h from admission to death. Advanced age(>65y), chronic liver disease, acute renal failure, requirement of ICU admission, and improper initial antibiotic use might be risk factors for poor prognosis. Even in survival cases, the foci of infection usually develop into fibrous scar tissue, or repeated infections requiring long-term antibiotic treatment. In our case, the patient developed necrotic pneumonia with cavity formation.
The progression and prognosis of such cases might be associated with various pathogeneses of P. aeruginosa [19, 20] :1)P. aeruginosa secretes toxins into the extracellular environment and into host cells. For example, through the type III secretion system (TTSS), P. aeruginosa injects toxins (e.g, ExoS, ExoT, ExoU) that change host cell activities and disrupt host cell actin cytoskeletons, block phagocytosis, and cause cell death; 2) Bacterial surface factors such as flagella, pili and lipopolysaccharide induce host inflammatory responses; 3) QS (quorum sensing), functioning as the connection between neighboring bacteria, plays a role in the regulation of a wide variety of processes including biofilm formation and production of numerous toxins; 4) P. aeruginosa secretes various enzymes and cytotoxins, such as elastase, alkaline protease and exotoxin A, that either disrupt the integrity of the epithelial barrier by disrupting epithelial cell tight junctions or cause direct tissue damage and necrosis.
The patient in this case developed rapid antimicrobial resistance to carbapenems. Despite a number of studies on antimicrobial resistance of hospital-acquired P. aeruginosa infection, the number of studies on resistance of community-acquired P. aeruginosa is limited. After analyzing drug sensitivity reports of 77 P. aeruginosa CAP cases, researchers found 32% were multi-drug resistant strains and 68% were sensitive strains . During treatment, these bacteria acquire antimicrobial resistance by several mechanisms, including reduced permeability, enzymatic degradation, and active efflux . Development of resistance is also associated with gene mutations. For example, repressed oprD expression leads to carbapenem resistance; mexX mutation causes resistance to aminoglycosides and fluoroquinolones . Mutations of gyrA and gyrB(gyrase) also result in resistance to fluoroquinolones . In addition, biofilm formation also contributes to antimicrobial resistance in P. aeruginosa. Biofilms are bacterial cities, highly organized, microbial communities encased in a polysaccharide matrix and attached to the surfaces of implants or airways. These multi-drug resistant variants in these colonies contribute to the high resistance of biofilms to antimicrobials.
Regarding treatment of P. aeruginosa CAP, guidelines recommend empirical treatment for these who have risk factors for P. aeruginosa infection. Early administration of proper antibiotics may improve the outcomes for such patients . For patients with suspected P. aeruginosa-caused severe pneumonia, combination antibiotic therapy should be administered within an hour . For critically ill patients admitted to the ICU, guidelines recommend use of an antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus an antipseudomonal fluoroquinolone; or the above β-lactam plus an aminoglycoside and azithromycin; or the aboveβ-lactam plus an aminoglycoside and a fluoroquinolone . Once P. aeruginosa is confirmed to be the pathogenic agent, antibiotic regimen should be adjusted to be more targeted. Targeted therapy recommended by guidelines includes an antipseudomonal β-lactam plus an aminoglycoside or a fluoroquinolone, with the alternative being an aminoglycoside plus a fluoroquinolone. According to a study by Cillóniz , inappropriate therapy occurred in 64 and 77% cases of P. aeruginosa CAP and multi-drug resistant P. aeruginosa CAP, respectively. In light of the high severity and rapid progression, patients with such conditions should be monitored closely and should receive frequent organ function evaluations.
According to our case and related literature review, we conclude that more attention should be paid to community-acquired Pseudomonas aeruginosa pneumonia because of its rapid progression and poor prognosis.